TW200414902A - Novel antibiotic compound, muraminomicin - Google Patents

Novel antibiotic compound, muraminomicin Download PDF

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TW200414902A
TW200414902A TW092132490A TW92132490A TW200414902A TW 200414902 A TW200414902 A TW 200414902A TW 092132490 A TW092132490 A TW 092132490A TW 92132490 A TW92132490 A TW 92132490A TW 200414902 A TW200414902 A TW 200414902A
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compound
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salt
heavy
methanol
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Yasunori Muramatsu
Yoko Fujita
Azusa Aoyagi
Masaaki Kizuka
Toshio Takatsu
Shunichi Miyakoshi
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Sankyo Co
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    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
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    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/16—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing two or more hetero rings
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    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/16—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing two or more hetero rings
    • C12P17/165—Heterorings having nitrogen atoms as the only ring heteroatoms
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    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/62—Streptosporangium

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Abstract

The present invention is related to a novel compound having the superior anti-bacterial activity, the microorganism producing the said compound, the preparing method of the said compound and the pharmaceutical composition (especially antimicrobial) containing the said compound as the effective ingredient.

Description

200414902 玖、發明說明： 【發明所屬之技術領域】 本發明係關於一種新穎化合物，其具有優異抗菌活性， 或作爲導致增強抗菌活性目的之相關衍生物之合成原料上 爲可能的，含有該化合物作爲有效成分之醫藥（特別是抗菌 劑），該化合物之製造方法’及生產該化合物之新穎微生物。 【先前技術】 向來細菌感染症之預防及治療上使用各種yg -內醯胺抗生 素、胺基配糖體、巨環類、肽聚醣、睦啉酮等，最近顯示 感染菌對此等抗生素之耐受性增加，因此冀望不同於先前 型式之抗生素。 細菌細胞壁構成成分上，關於肽聚糖生合成之轉位酵素 (translocase) I爲細菌生長上之必須酵素，近年，基於對 轉位酵素I之抑制活性，已報告對於分枝桿菌屬 (M y c o b a c t e r i u m )之細菌顯示抗菌活性之化合物，利波希 朵黴素（liposidomycin)類及卡派拉黴素（caprazamycin)類等 (例如參閱專利文獻1、非專利文獻1及非專利文獻2)。 (專利文獻1) 國際公開第0 1 / 1 2643號公報 (非專利文獻1) 抗生素雜誌，1 98 5年，第38卷，P.1617-1621 (J. Antibiotics, 1 9 8 5, 3 8, pl617-1621) (非專利文獻2) 農業生.物化學，1 989年，第53卷，P.1811-1815 200414902 (Agric.Biol.Chem，1 98 9，53，ρ·1811-1815) 【發明內容】 本發明者們於培養液中發現新穎化合物，不斷進行此等 化合物之藥理活性硏究之結果，發線此等化合物具有對轉 位酵素I抑制活性之抗菌活性，而與先前型式之藥劑無交叉 耐受性’同時又發現較先前已知化合物有較優異之抗菌活 性’確立生產該化合物之新穎微生物及該化合物之製造方 法，因而完成本發明。 本發明爲： (1)下列一般式（I)，200414902 发明 Description of the invention: [Technical field to which the invention belongs] The present invention relates to a novel compound which has excellent antibacterial activity, or is a possible raw material for related derivatives leading to the purpose of enhancing antibacterial activity, containing the compound as Medicines with active ingredients (especially antibacterial agents), methods for producing the compounds' and novel microorganisms for producing the compounds. [Previous technology] Various yg-lactam antibiotics, aminoglycosides, macrocyclics, peptidoglycans, and azolinones have been used in the prevention and treatment of bacterial infections. Recently, infectious bacteria have shown that Tolerance is increased, so expect different antibiotics from the previous version. On the constituent components of bacterial cell walls, translocase I, which is a biosynthesis of peptidoglycan, is an essential enzyme for bacterial growth. In recent years, based on the inhibitory activity of translocase I, it has been reported for Mycobacterium ), Compounds exhibiting antibacterial activity, such as liposidomycins and caprazamycins (see, for example, Patent Document 1, Non-Patent Document 1 and Non-Patent Document 2). (Patent Document 1) International Publication No. 01/1263 (Non-Patent Document 1) Journal of Antibiotics, 1985, Vol. 38, P.1617-1621 (J. Antibiotics, 1 9 8 5, 3 8 (pl617-1621) (Non-Patent Document 2) Agricultural Biophysical Chemistry, 1989, Vol. 53, P.1811-1815 200414902 (Agric. Biol. Chem, 1 98 9, 53, ρ · 1811-1815) [Summary of the invention] The present inventors found novel compounds in the culture medium, and continued to investigate the pharmacological activities of these compounds. As a result, these compounds have antibacterial activity against the inhibitory activity of translocation enzyme I, which is in contrast to the previous type. The drug has no cross-tolerance, and at the same time, it has found that it has better antibacterial activity than previously known compounds. It established a novel microorganism for producing the compound and a method for producing the compound, and thus completed the present invention. The invention is: (1) the following general formula (I),

[式中，R爲煙鏈]所示化合物或其鹽。 (2) 如（1)記載之化合物或其鹽，R爲飽和烴鏈。 (3) 如（2)記載之化合物或其鹽，r爲直鏈狀飽和烴鏈。 (4) 如（3)記載之化合物或其鹽，r爲碳數？至17之直鏈狀飽和 烴鏈。 (5) 如（4)sg載之化合物或其鹽，&爲碳數卩至。之直鏈狀飽和 烴鏈。 (6) 如（5)記載之化合物或其鹽，R表示_(CH2)9CH3或- (ch2)10ch3。 (7) 如（2)記載之化合物或其鹽，r表示彳ch2)8CH(CH3)2。 (8) 如（1)記載之化合物或其鹽，r爲直鏈狀不飽和烴鏈。 (9) 如（8)記載之化合物或其鹽，&表示- (ch2)3ch = ch(ch2)5cH3、 _CH2CH = CH(CH2)7CH3、- (CH2)3CH = CHCH2CH = CH(CH2)4CH3、或_ (ch2)3ch = ch(ch2)6cH3。 (10) 下列一般式（II)，[Wherein R is a smoke chain] or a salt thereof. (2) The compound or a salt thereof according to (1), wherein R is a saturated hydrocarbon chain. (3) The compound or a salt thereof according to (2), wherein r is a linear saturated hydrocarbon chain. (4) If the compound or its salt as described in (3), is the carbon number? To 17 straight linear saturated hydrocarbon chains. (5) If the compound or salt thereof contained in (4) sg, & The linear saturated hydrocarbon chain. (6) The compound or a salt thereof according to (5), wherein R represents _ (CH2) 9CH3 or-(ch2) 10ch3. (7) The compound or a salt thereof according to (2), wherein r represents 彳 ch2) 8CH (CH3) 2. (8) The compound or a salt thereof according to (1), wherein r is a linear unsaturated hydrocarbon chain. (9) The compound or its salt as described in (8), & represents-(ch2) 3ch = ch (ch2) 5cH3, _CH2CH = CH (CH2) 7CH3,-(CH2) 3CH = CHCH2CH = CH (CH2) 4CH3 , Or _ (ch2) 3ch = ch (ch2) 6cH3. (10) the following general formula (II),

[式中’ R爲烴鏈]所示化合物或其鹽。 (1 1)如（10)記載之化合物或其鹽，R爲直鏈狀飽和烴鏈。 (12) 如（1 1)記載之化合物或其鹽，R爲碳數7至丨7之直鏈狀飽 和烴鏈。 (13) 如（12)記載之化合物或其鹽，r爲碳數9至15之直鏈狀飽 和烴鏈。 (1 4 )如（1 3 )記載之化合物或其鹽 ，R表示（CH2)10CH3。 (15)下列一般式（III)，[Wherein R is a hydrocarbon chain] or a salt thereof. (1 1) The compound or a salt thereof according to (10), wherein R is a linear saturated hydrocarbon chain. (12) The compound or a salt thereof according to (1), wherein R is a linear saturated hydrocarbon chain having 7 to 7 carbon atoms. (13) The compound or a salt thereof according to (12), wherein r is a linear saturated hydrocarbon chain having 9 to 15 carbon atoms. (1 4) The compound or a salt thereof according to (1 3), wherein R represents (CH2) 10CH3. (15) the following general formula (III),

[式中，R爲烴鏈]所示化合物或其鹽。 (16) 如（15)記載之化合物或其鹽，R爲直鏈狀飽和烴鏈。 (17) 如（16)記載之化合物或其鹽，R爲碳數7至17之直鏈狀飽 和烴鏈。 (18) 如（17)記載之化合物或其鹽，R爲碳數9至15之直鏈狀飽 和烴鏈。 (19) 如（18)記載之化合物或其鹽，R表示-(CH2)1()CH3。 (20) 下列一般式（IV)，[Wherein R is a hydrocarbon chain] or a salt thereof. (16) The compound or a salt thereof according to (15), wherein R is a linear saturated hydrocarbon chain. (17) The compound or a salt thereof according to (16), wherein R is a linear saturated hydrocarbon chain having 7 to 17 carbon atoms. (18) The compound or a salt thereof according to (17), wherein R is a linear saturated hydrocarbon chain having 9 to 15 carbon atoms. (19) The compound or a salt thereof according to (18), wherein R represents-(CH2) 1 () CH3. (20) the following general formula (IV),

[式中，R爲烴鏈]所示化合物或其鹽。 200414902 (21) 如（2〇)記載之化合物或其鹽 (22) 如（21)記載之化合物或其= 和烴鏈。 (2 3 )如（2 2)記載之化合物或其臨 和烴鏈。 ，R爲直鏈狀飽和烴鏈。 ，R爲碳數7至17之直鏈狀飽 ，R爲碳數9至15之直鏈狀飽 (24) 如（23)記載之化合物或其鹽，r表示 (25) 下列一般式（V)所示化合物或其鹽，[Wherein R is a hydrocarbon chain] or a salt thereof. 200414902 (21) The compound according to (20) or a salt thereof (22) The compound according to (21) or a hydrocarbon chain thereof. (2 3) The compound according to (2 2) or a temporary hydrocarbon chain thereof. R is a linear saturated hydrocarbon chain. R is a straight-chain saturated group having 7 to 17 carbon atoms, R is a straight-chain saturated group having 9 to 15 carbon atoms (24) The compound or a salt thereof as described in (23), and r represents (25) the following general formula (V ) Compound or salt thereof,

(V) (26)下列一般式（VI)所示化合物或其鹽，(V) (26) a compound represented by the following general formula (VI) or a salt thereof,

(2 7 )下列一般式（V11)所7^化合物或其鹽， -10- 200414902(2 7) The compound or its salt represented by the following general formula (V11), -10- 200414902

(VII) (28)下列一般式（VIII)所示化合物或其鹽，(VII) (28) a compound represented by the following general formula (VIII) or a salt thereof,

(VIII) (2 9)—種如（1)至（28)或⑴至（xii)中任1項記載之化合物之製 造方法，其特徵爲培養生產（1)至（28)或（i)至（xii)中任1 項記載之化合物之生產菌鏈孢囊菌屬 (Streptosporangium)，由其培養物中收集（1)至（28) 或（i)至（X i i)中任1項記載之化合物。 (3 0)如（2 9)記載之製造方法，其中該培養係於含脂肪酸之培 養基中進行。 (3 1)如（3 0)記載之製造方法，其中該脂肪酸爲碳數10至20之 直鏈狀飽和脂肪酸。 (32)如（31)記載之製造方法，其中脂肪酸.爲碳數I2至18之直 -11- 200414902 鏈狀飽和脂肪酸。 (3 3)如（29)至（3 2)中任1項記載之製造方法，其中培養生產（1) 至（28)或（i)至（XII)中任1項記載之化合物之生產菌鏈孢 囊菌屬（Streptosporangium)，爲鏈孢囊菌屬 (S treptosporangium sp . ) S ANK6 05 0 1 (FERM BP_ 7984) ° (34) —種特徵爲生產（1)至（28)或⑴至（xii)中任l項記載之化 合物之微生物鏈孢囊菌屬（Streptosporangium sp)。 (35) — 種鏈孢囊菌屬（Streptosporan gium sp ) S ANK60 5 0 1 (FERM BP-7984)。 (36) —種製造如（21)或（viii)中之記載化合物之方法，其係 將（1)至（19)、（i)至（Vii)及（X)至（Xi)中任1項記載之化合 物水解或還原。 (37) —種製造如（22)或（ix)中記載之化合物之方法，其係將（1) 至（19)、（i)至（vii)及（X)至（xi)中任〗項記載之化合物水 解或還原。 (38) —種製造如（27)中記載之化合物之方法，其係將（2〇)至 (24)及（xii)中任1項記載之化合物水解或還原。 (39) —種製造如（28)中記載之化合物之方法，其係將（20)至 (24)及（xii)中任丨項記載之化合物水解或還原。 (40) —種醫藥組成物，其含有（1)至（28)或⑴至（xii)中任^頁 記載之化合物或其藥理學上容許鹽爲有效成分。 (41) 如（4〇)中記載之醫藥組成物，其爲一種抗菌劑。 (42) —種細菌感染症之治療方法，其包含將有效量之（1)至 -12- 200414902 (28)或⑴至（xii)中任1項記載之化合物或其藥理學上容 許鹽投與病患。 (43)—種如（1)至（28)或⑴至（xii)中任！項記載之化合物或其 藥理學上容許鹽之用途，其用於製造抗菌劑。 又，本發明係關於下列記載之化合物： ⑴ 一種具有下述物理化學性狀之化合物或其鹽： 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞碾，不溶於氯仿 3) 分子式：C55H85N 50 2 3 4) 分子量：1183(以FAB質譜法測定） 5 )依高分解能F A B質譜法測定之精密質量，[μ + Η ] +如下列 表示： 實測値：1 1 84.5 69 9 計算値：1 1 8 4 · 5 7 1 3 6) 紫外線吸收光譜： 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表示： 263nm( ε 9200) 7) 旋光度： 於甲醇中測定旋光度，如下列所示値表示： [α]〇29 ： +7.5° ( c0.5) 8) 紅外線吸收光譜： 以溴化鉀（ΚΒι:)錠劑法測定之紅外線吸收光譜以下列所 示之極大吸收表示： -13- 200414902 3414,2928,2856,1738,1696,1631，1465,1384,1273,1161， 1 1 27,1 1 04,1 0 1 5,960cm·1 9) 1H-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞楓（2.4 9ppm)測 定’以下所示爲其1H-核磁共振光譜： 〇.84(6H，t)，〇.9 1(3H，d，J = 6.2Hz)，1.2-1.3(10H，m)，1.42(lH， m)，1.57(2H，m)，1.71(lH，m),2.0(7H，m)，2.12(lH，m)，2.16(lH， m)，2.26(3H，s)，2.3(3H，m)，2.4 1(lH，m)，2.46(2H，m)，2.6(4H， m)，2.80(lH，dd，J = 6.6，12.8Hz)，2.92(3H，s)，2.94(lH，m)52.98 (lH，br.m)，3.26(lH，t，J = 9.2Hz)，3.36(3H，s)，3.37(3H，s)，3.4 (2H，m)，3.53(lH，m)，3.83(lH，d，J = 8.4Hz)，3.9(3H，m)，4.13(l H，m)，4.19(2H，m)54.96(lH，dd，J = 2.9,9.2Hz)，5.12(lH，m)，5.3 (2H，m)，5.37(2H，m)，5.65(lH，d，J = 7.7Hz)，5.90(lH，t，J = 5.9H z)，5.93(lH，m)，7.82(lH，d，J = 7.7)ppm 10) 13c_核磁共振光譜： 重一甲亞碾中，內部標準使用重二甲亞碾（3 9 · 5 p p m )測 定’以下所示爲其13C -核磁共振光譜： 9.5(q)，14.〇(q)，1 9.0(q)，22. 1 (t )，23.9 (t)，24.8(t)，26·3(〇,26·6 (t)，27.1(d)，28.3(t)，2 8.7(t)，29.1(t)，9.2(t)，3 1 .2(t)，3 2.9(t)，3 6.4(q)，3 7.8(q)，3 8.8(t)，9.8(t)，39.9(t)，40.2(t)，40.6(t)，4 1.5( t)，5 6.6(t)，8.7(q)56 0.0 (q),62.3(d)，66.5(d)，69.0(d)，69.9(d)· 70.6(d)，72.7(d)，73.0(d)，74·1(d).76.6(d),77.3(d)，77.5(d)，8 2.〇(d) 5 8 3.9 (d),87.4(d),90.5(d), 101.3(d) ,106.8(d),129.1(d), 13 0.1(d), 140.5(d), 150.2 (s)?163.3 (s),16 8.7(s)? 169.2(s)5l 7 -14- 200414902 0.1(s)，170.7(s)，171 .l(s).171.g(s).173.6(s) ppm 11) 高速液體色層分析法： 管柱· CAPCELLPAKC18UG120,4.6px 150mm (資生堂股 份有限公司製） 溶劑：含有1 〇 m Μ重碳酸銨之4 0 %乙腈水溶液 流速：1 · 〇 m 1 /分鐘 檢出：紫外線吸收260nm 保持時間：9.3分鐘 (Π) ^ 具有下列物理化學性狀之化合物或其鹽： 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞碾，不溶於氯仿 3) 分子式：C55H85N5 023 4) 分子量：1171(以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[Μ + ΗΓ如下歹 表不: 實測値：1 1 7 2.5 7 0 4 計算値：1 1 7 2.5 7 1 3 6) 紫外線吸收光譜： 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表$ . 263 nm( ε 9 1 00) 7) 旋光度： 於甲醇中測定旋光度，如下列所示値表示： [a ]D29 : +6.3。 （ c0.2 ) -15- 200414902 8) 紅外線吸收光譜： 以溴化鉀（KB r )錠劑法測定之紅外線吸收光譜以下列所 示之極大吸收表示： 3403,2927,2855,1 738,1691，163 1，1466,1385, 1273,1 161， 1 104,1014,961cm'1 9) 4-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞碾（2.49ppm )測 定’以下所示爲其1H-核磁共振光譜： 0.84(6H，t)，0.92(3H，d，J = 5.9Hz)，1.2-1.3(16H，m)，1.42(lH， φ m)，1.5 5(2H，m)，1.7 1(lH，m)，2.0(3H，m)，2.14(2H，m)，2.26(3H， s)，2.3(3H，m)，2.4 1(lH，m)，2.47(2H，m)，2.6(4H，m)，2.80(lH，d d5J = 6.9，13.7Hz)，2.92(3H，s)，2.93(lH，bi:.m)，3.01(lH5dd，J = 2· 9,13.7Hz)，3.27(lH，t，J = 9.3Hz)，3.3 6(3H，s)，3.37(3H，s)，3.38 (lH，m)53.40(lH，m)，3 .53(1 H，t，J = 2.4Hz)，3.86(1 H，d，J = 8.8H z)，3.9(2H，m)，3.97(lH，m)，4.13(lH，m)，4.18(2H,m)，4.96(lH， dd5J = 2.9,9.3Hz)，5.11(lH5m),5.38(2H，m)，5.66(lH，d，J = 8.3H z)，5·90(1Η，t，J = 5.9Hz)，5.93(1 H，m)，7.82(lH，d，J = 8.3 Hz )p pm _ 1 0 )13 c -核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞礪（3 9.5 ppm )測 定，以下所示爲其13C -核磁共振光譜： 9.5(q)，14.0(q)，19.0(q)，22.1(t)，23.9(t)，24.5(t)，27.2(d)，2 8· 7(t)，28.9(0).29.0(t)，29.1(d)，3 1.3(t)，3 3.3(t)，36.4(q)，37.8 U)，3 9.4(t)，3 9.6(t)，3 9.8(t)，39.9(t)，40.7(t)，41.5(t)，5 6.5(t)， 58.7(q)，60.〇(q)，62.3(d)，66.6(d),69.1(d)，70.0(d)，70.7(d)，7 -16- 200414902 2.7(d)，73.0(d)，74.1(d)，76.6(d)，77.3(d)，77.6 (d)，82.0(d)，8 4.0(d)，87.4(d)，90.4(d)，101.3(d)，106.8 (d)，140.5(d)，150.2 (s)，163.3(s)，168.5(s).169.3(s)，170.1(s)，170.6(s)，171.1(s)， 171 .8(s)51 73.5(s)ppm 1 1)高速液體色層分析法： 管柱：CAPCELLPAK C18UG120,4.6px 150mm (資生堂股 份有限公司製） 溶劑：含有l〇mM重碳酸銨之40%乙腈水溶液 流速：1.0ml/分鐘 檢出：紫外線吸收260nm 保持時間：9.8分鐘 (iii) 具有下列物理化學性狀之化合物或其鹽： 1 )物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞楓，不溶於氯仿 3) 分子式：C55H85N5 023 4) 分子量：1183(以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[Μ + ΗΓ如下列 表示： 實測値：1 1 84.5 72 3 計算値：1 1 8 4.5 7 1 4 6) 紫外線吸收光譜： 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表示： 26 3 nm( ε 8 100) 200414902 7)旋光度： 於甲醇中測定旋光度，如下列所示値表示： [a ]D29 : +6·5。（ c0.2 ) 8 )紅外線吸收光譜： 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下列所 不之極大吸收表示： 3403,292 7,2855,1738,1690,1 63 1，1466,1385,1273,1 162， 1 1 〇45 1 0 1 5,962cm'1 9) 4-核磁共振光譜： 鲁 重二甲亞楓中，內部標準使用重二甲亞碾（2.4 9ppm )測 定，以下所示爲其1H-核磁共振光譜： 0.84(6H，t)，0.91(3H，d，J = 6.0Hz)，1.2-1.3(12H，m)，1.42(lH， m)，1.70(lH，m)，2.0(5H，m),2.14(2H，m)，2.26(3H，s)，2.3(4H， m)，2.42(lH，m)，2.5(2H，m)，2.6(4H，m)，2.80(lH，dd，J = 6.8，12. 8Hz)，2.9 1(3H，s)，2.95(lH，br.m)，3.0 1(lH，dd，J = 2.6，12.8Hz)， 3.27(lH，t，J = 9.0Hz)，3.36(3H，s)，3.37(3H，s)，3.4(2H，m)，3.53 (lH，m)，3.85(lH，d，J = 8.1Hz)，3.9(2H，m)，3.96(lH，m)，4.13(l · H，m)，4.19(2H，m).4.96(lH，dd5J = 2.6,9.4Hz)，5.13(lH,m)，5.3 0(lH，dt，J = 7.3,9.8Hz)，5.38(2H，m)，5.47(lH，dt，J = 7.3,9.8Hz)， 5.66(lH，d，J = 8.1Hz)55.90(lH，t,J = 5.6Hz)，5.93(lH，m)，7.82(l H，d，J = 8 .lHz)ppm 10) 13C-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞碾（39.5ppm)測 定，以下所示爲其13C -核磁共振光譜： -18- 200414902 9.5(q)，14.0(q)，19.0(q)，22.1(t)，23.9(t)，26.7(t)，27.1(d)，28. 7(t)，28.7(t).28.9(t)，28.9(t)529.0(t)，29.0(t)，29.1(t)，3 1.3(t)， 33.1(t)，36.4(q)，3 7.8(q)，3 8.2(t)，39.8(t)，3 9.9(t)，40.2(t)，40. 7(t)，4 1 .5(t)，5 6.6(t)，5 8.7(q)，60.0(q)，62· 3(d)，66.5(d)，69· 1( d)，69.8(d)，70.7(d)，72.7(d)，73 ·0(〇[)，74· 1(d)，76.6(d)，77.3(d )，77.5(d)，82.0(d)，84.0(d)，87.4(d)，90.5(d)，101.3(d)，106.8 (d)，123.6(d)，133.1(d)，140.5(d)，150.2(s)，163.3(s)，168.6(s)， 169.3(s)，170.2(s)，170.6(s)，171.0(s)，171.8(s)，173.5(s)ppm 1 1)高速液體色層分析法： 管柱：CAPCELLPAK C18UG120,4.6px 150mm (資生堂股 份有限公司製） 溶劑：含有10mM重碳酸銨之40%乙腈水溶液 流速：1 . 0 m 1 /分鐘 檢出：紫外線吸收260nm 保持時間：1 〇 . 9分鐘 (iv) 具有下列物理化學性狀之化合物或其鹽： 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞楓，不溶於氯仿 3) 分子式：C57H87N5023 6) 分子量：1 209(以FAB質譜法測定） 7) 依高分解能FAB質譜法測定之精密質量，[M + H] +如下列 表示： 實測値：1 2 1 0.5 8 6 7 200414902 計算値：1210.5870 6) 紫外線吸收光譜： 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表示： 263nm( ε 9900) 7) 旋光度： 於甲醇中測定旋光度，如下列所示値表示： [a ]D29 : +1 3.2。（ c0.2 ) 8) 紅外線吸收光譜： 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下列所 示之極大吸收表示： 3383，2957,2930,1738,1695,1629,1464,1384，1273，ll61 1 1 04,1 0 1 4,960cm·1 9) 1H-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞楓（2.49ppm >測 定，以下所示爲其1 Η -核磁共振光譜：(VIII) (2 9) —A method for producing a compound according to any one of (1) to (28) or ⑴ to (xii), which is characterized by culture production (1) to (28) or (i) Streptosporangium producing compounds of any one of (1) to (xii) is collected from the culture of (1) to (28) or (i) to (X ii) Of compounds. (30) The production method according to (29), wherein the culturing is performed in a medium containing a fatty acid. (3 1) The production method according to (30), wherein the fatty acid is a linear saturated fatty acid having 10 to 20 carbon atoms. (32) The production method according to (31), wherein the fatty acid is a straight chain saturated fatty acid having a carbon number of I2 to 18 -11-200414902. (3 3) The production method according to any one of (29) to (3 2), wherein the production bacteria producing the compound according to any one of (1) to (28) or (i) to (XII) are cultured. Streptosporangium (Septeptosporangium sp.) S ANK6 05 0 1 (FERM BP_ 7984) ° (34) — features characterized by production (1) to (28) or ⑴ to (Xii) The microorganism of the compound described in any one of item l to Streptosporangium sp. (35) — Streptosporan gium sp. S ANK60 5 0 1 (FERM BP-7984). (36) A method for producing a compound as described in (21) or (viii), which is any one of (1) to (19), (i) to (Vii), and (X) to (Xi) The compound described in this item is hydrolyzed or reduced. (37) A method for producing a compound as described in (22) or (ix), which is any one of (1) to (19), (i) to (vii), and (X) to (xi) The compound described in this item is hydrolyzed or reduced. (38) A method for producing a compound according to (27), which comprises hydrolyzing or reducing the compound according to any one of (20) to (24) and (xii). (39) A method for producing a compound as described in (28), which hydrolyzes or reduces the compound described in any one of (20) to (24) and (xii). (40) A pharmaceutical composition comprising the compound described in any one of (1) to (28) or (ii) to (xii) or a pharmacologically acceptable salt thereof as an active ingredient. (41) The pharmaceutical composition according to (4), which is an antibacterial agent. (42) A method for treating a bacterial infection, comprising administering an effective amount of the compound described in any one of (1) to -12-200414902 (28) or (1) to (xii) or a pharmacologically acceptable salt thereof. With the patient. (43) —Species such as (1) to (28) or ⑴ to (xii)! The use of the compound or the pharmacologically acceptable salt thereof according to the above item for producing an antibacterial agent. In addition, the present invention relates to the following compounds: ⑴ A compound or a salt thereof having the following physical and chemical properties: 1) Properties of the substance: a colorless powdery substance 2) Solubility: soluble in methanol and dimethylamine, Insoluble in chloroform 3) Molecular formula: C55H85N 50 2 3 4) Molecular weight: 1183 (determined by FAB mass spectrometry) 5) Precision mass determined by high decomposition energy FAB mass spectrometry, [μ + Η] + as shown below: Measured 値: 1 1 84.5 69 9 Calculated 1: 1 1 8 4 · 5 7 1 3 6) Ultraviolet absorption spectrum: The ultraviolet absorption spectrum is measured in methanol, and the maximum absorption is shown as follows: 263nm (ε 9200) 7) Optical rotation: in methanol The degree of optical rotation is measured as shown below: [α] 〇29: + 7.5 ° (c0.5) 8) Infrared absorption spectrum: The infrared absorption spectrum measured by potassium bromide (KB): tablet method is as follows The maximum absorption shown is: -13- 200414902 3414,2928,2856,1738,1696,1631,1465,1384,1273,1161, 1 1 27,1 1 04,1 0 1 5,960cm · 1 9) 1H- Nuclear Magnetic Resonance Spectroscopy: In heavy dimethanine, the internal standard was determined using heavy dimethanine (2.4 9ppm) 'Its 1H-NMR spectrum is shown below: 0.84 (6H, t), 0.91 (3H, d, J = 6.2Hz), 1.2-1.3 (10H, m), 1.42 (lH, m ), 1.57 (2H, m), 1.71 (lH, m), 2.0 (7H, m), 2.12 (lH, m), 2.16 (lH, m), 2.26 (3H, s), 2.3 (3H, m) , 2.4 1 (lH, m), 2.46 (2H, m), 2.6 (4H, m), 2.80 (lH, dd, J = 6.6, 12.8 Hz), 2.92 (3H, s), 2.94 (lH, m) 52.98 (lH, br.m), 3.26 (lH, t, J = 9.2Hz), 3.36 (3H, s), 3.37 (3H, s), 3.4 (2H, m), 3.53 (lH, m), 3.83 (lH, d, J = 8.4 Hz), 3.9 (3H, m), 4.13 (l H, m), 4.19 (2H, m) 54.96 (lH, dd, J = 2.9, 9.2 Hz), 5.12 (lH, m), 5.3 (2H, m), 5.37 (2H, m), 5.65 (lH, d, J = 7.7Hz), 5.90 (lH, t, J = 5.9Hz), 5.93 (lH, m), 7.82 (lH, d, J = 7.7) ppm 10) 13c_NMR spectrum: In heavy-duty secondary mills, internal standards were determined using heavy-duty secondary mills (3 9 · 5 ppm). '13C-NMR shown below Resonance spectra: 9.5 (q), 14.〇 (q), 1 9.0 (q), 22. 1 (t), 23.9 (t), 24.8 (t), 26.3 (0, 26.6 (t) , 27.1 (d), 28.3 (t), 2 8.7 (t), 29.1 (t), 9.2 (t), 3 1.2 (t), 3 2. 9 (t), 3 6.4 (q), 3 7.8 (q), 3 8.8 (t), 9.8 (t), 39.9 (t), 40.2 (t), 40.6 (t), 4 1.5 (t), 5 6.6 (t), 8.7 (q) 56 0.0 (q), 62.3 (d), 66.5 (d), 69.0 (d), 69.9 (d) 70.6 (d), 72.7 (d), 73.0 (d), 74 · 1 (d). 76.6 (d), 77.3 (d), 77.5 (d), 8 2.〇 (d) 5 8 3.9 (d), 87.4 (d), 90.5 (d), 101.3 (d) , 106.8 (d), 129.1 (d), 13 0.1 (d), 140.5 (d), 150.2 (s)? 163.3 (s), 16 8.7 (s)? 169.2 (s) 5l 7 -14- 200414902 0.1 ( s), 170.7 (s), 171.1 (s) .171.g (s) .173.6 (s) ppm 11) High-speed liquid chromatography analysis method: column CAPCELLPAKC18UG120, 4.6px 150mm (made by Shiseido Co., Ltd. ) Solvent: 40% acetonitrile aqueous solution containing 10 mM ammonium bicarbonate. Flow rate: 1.0 m 1 / min. Detection: UV absorption at 260 nm. Hold time: 9.3 minutes. (II) ^ Compounds having the following physical and chemical properties or their Salt: 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethyl isocyanate, insoluble in chloroform 3) Molecular formula: C55H85N5 023 4) Molecular weight: 1171 (determined by FAB mass spectrometry) 5) The precise mass determined by high resolution energy FAB mass spectrometry, [Μ + 歹 Γ is as follows] Table: Measured 値: 1 1 7 2.5 7 0 4 Calculated 値: 1 1 7 2.5 7 1 3 6) Ultraviolet absorption spectrum: Measure the ultraviolet absorption spectrum in methanol. The maximum absorption table is shown below. 263 nm (ε 9 1 00) 7) Optical rotation: Measure the optical rotation in methanol, as shown below: [a] D29: +6.3. (C0.2) -15- 200414902 8) Infrared absorption spectrum: The infrared absorption spectrum measured by the potassium bromide (KB r) tablet method is expressed by the maximum absorption shown below: 3403, 2927, 2855, 1 738, 1691 , 163 1,1466,1385, 1273,1 161, 1 104,1014,961cm'1 9) 4-Nuclear Magnetic Resonance Spectroscopy: Among heavy dimethylformaldehyde mills, the internal standard was determined using heavy dimethylformaldehyde mills (2.49ppm). Its 1H-NMR spectrum is shown below: 0.84 (6H, t), 0.92 (3H, d, J = 5.9Hz), 1.2-1.3 (16H, m), 1.42 (lH, φ m), 1.5 5 ( 2H, m), 1.7 1 (lH, m), 2.0 (3H, m), 2.14 (2H, m), 2.26 (3H, s), 2.3 (3H, m), 2.4 1 (lH, m), 2.47 (2H, m), 2.6 (4H, m), 2.80 (lH, d5J = 6.9, 13.7Hz), 2.92 (3H, s), 2.93 (lH, bi: .m), 3.01 (lH5dd, J = 2 9,13.7 Hz), 3.27 (lH, t, J = 9.3 Hz), 3.36 (3H, s), 3.37 (3H, s), 3.38 (lH, m) 53.40 (lH, m), 3.53 (1 H, t, J = 2.4 Hz), 3.86 (1 H, d, J = 8.8 H z), 3.9 (2H, m), 3.97 (lH, m), 4.13 (lH, m), 4.18 (2H , m), 4.96 (lH, dd5J = 2.9, 9.3 Hz), 5.11 (lH5m), 5.38 (2H, m), 5.66 (lH, d, J = 8.3H z), 5.90 (1Η, t J = 5.9 Hz), 5.93 (1 H, m), 7.82 (lH, d, J = 8.3 Hz) p pm _ 1 0) 13 c-Nuclear magnetic resonance spectrum: heavy dimethyline, internal standard uses double The measurement of Jia Yalan (3 9.5 ppm) is shown below as its 13C-NMR spectrum: 9.5 (q), 14.0 (q), 19.0 (q), 22.1 (t), 23.9 (t), 24.5 (t) , 27.2 (d), 2 8.7 (t), 28.9 (0). 29.0 (t), 29.1 (d), 3 1.3 (t), 3 3.3 (t), 36.4 (q), 37.8 U), 3 9.4 (t), 3 9.6 (t), 3 9.8 (t), 39.9 (t), 40.7 (t), 41.5 (t), 5 6.5 (t), 58.7 (q), 60.〇 (q) , 62.3 (d), 66.6 (d), 69.1 (d), 70.0 (d), 70.7 (d), 7 -16- 200414902 2.7 (d), 73.0 (d), 74.1 (d), 76.6 (d) , 77.3 (d), 77.6 (d), 82.0 (d), 8 4.0 (d), 87.4 (d), 90.4 (d), 101.3 (d), 106.8 (d), 140.5 (d), 150.2 (s ), 163.3 (s), 168.5 (s). 169.3 (s), 170.1 (s), 170.6 (s), 171.1 (s), 171.8 (s) 51 73.5 (s) ppm 1 1) High-speed liquid color Layer analysis method: Column: CAPCELLPAK C18UG120, 4.6px 150mm (made by Shiseido Co., Ltd.) Solvent: 40% acetonitrile aqueous solution containing 10 mM ammonium bicarbonate Flow rate: 1.0 ml / min Detection: UV absorption at 260 nm Hold time 9.8 minutes (iii) A compound or a salt thereof having the following physical and chemical properties: 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethyl sulfoxide, and insoluble in chloroform 3) Molecular formula: C55H85N5 023 4) Molecular weight: 1183 (determined by FAB mass spectrometry) 5) Precise mass determined by high decomposition energy FAB mass spectrometry, [Μ + ΗΓ is expressed as follows: Measured 値: 1 1 84.5 72 3 Calculated 値: 1 1 8 4.5 7 1 4 6) Ultraviolet absorption spectrum: The ultraviolet absorption spectrum is measured in methanol, and the maximum absorption is shown as follows: 26 3 nm (ε 8 100) 200414902 7) Optical rotation: The optical rotation is measured in methanol, as shown below: : [A] D29: +6.5. (C0.2) 8) Infrared absorption spectrum: The infrared absorption spectrum measured by potassium bromide (KBr) lozenge method is expressed by the following maximum absorption: 3403,292 7,2855,1738,1690,1 63 1, 1466,1385,1273,1 162, 1 1 〇45 1 0 1 5,962cm'1 9) 4-Nuclear Magnetic Resonance Spectroscopy: In the heavy dimethyline, the internal standard is determined by the heavy dimethyline (2.4 9ppm), Its 1H-NMR spectrum is shown below: 0.84 (6H, t), 0.91 (3H, d, J = 6.0Hz), 1.2-1.3 (12H, m), 1.42 (lH, m), 1.70 (lH, m), 2.0 (5H, m), 2.14 (2H, m), 2.26 (3H, s), 2.3 (4H, m), 2.42 (lH, m), 2.5 (2H, m), 2.6 (4H, m ), 2.80 (lH, dd, J = 6.8, 12.8 Hz), 2.9 1 (3H, s), 2.95 (lH, br.m), 3.0 1 (lH, dd, J = 2.6, 12.8 Hz), 3.27 (lH, t, J = 9.0 Hz), 3.36 (3H, s), 3.37 (3H, s), 3.4 (2H, m), 3.53 (lH, m), 3.85 (lH, d, J = 8.1Hz) , 3.9 (2H, m), 3.96 (lH, m), 4.13 (l · H, m), 4.19 (2H, m). 4.96 (lH, dd5J = 2.6,9.4Hz), 5.13 (lH, m), 5.3 0 (lH, dt, J = 7.3, 9.8 Hz), 5.38 (2H, m), 5.47 (lH, dt, J = 7.3, 9.8 Hz), 5.66 (lH, d, J = 8.1 Hz) 55. 90 (lH, t, J = 5.6 Hz), 5.93 (lH, m), 7.82 (l H, d, J = 8. lHz) ppm 10) 13C-NMR spectrum: heavy dimethanine, internal standard Measured by heavy dimethanine (39.5ppm), and its 13C-NMR spectrum is shown below: -18- 200414902 9.5 (q), 14.0 (q), 19.0 (q), 22.1 (t), 23.9 (t ), 26.7 (t), 27.1 (d), 28.7 (t), 28.7 (t). 28.9 (t), 28.9 (t) 529.0 (t), 29.0 (t), 29.1 (t), 3 1.3 (t), 33.1 (t), 36.4 (q), 3 7.8 (q), 3 8.2 (t), 39.8 (t), 3 9.9 (t), 40.2 (t), 40.7 (t), 4 1.5 (t), 5 6.6 (t), 5 8.7 (q), 60.0 (q), 62.3 (d), 66.5 (d), 69.1 (d), 69.8 (d), 70.7 ( d), 72.7 (d), 73.0 (〇 [), 74.1 (d), 76.6 (d), 77.3 (d), 77.5 (d), 82.0 (d), 84.0 (d), 87.4 ( d), 90.5 (d), 101.3 (d), 106.8 (d), 123.6 (d), 133.1 (d), 140.5 (d), 150.2 (s), 163.3 (s), 168.6 (s), 169.3 ( s), 170.2 (s), 170.6 (s), 171.0 (s), 171.8 (s), 173.5 (s) ppm 1 1) High-speed liquid chromatography analysis method: Column: CAPCELLPAK C18UG120, 4.6px 150mm (Shiseido Shares Co., Ltd.) Solvent: 40% acetonitrile aqueous solution containing 10mM ammonium bicarbonate : 1.0 m 1 / min Detection: UV absorption at 260 nm Holding time: 1 0.9 minutes (iv) Compound or salt thereof having the following physicochemical properties: 1) Properties of the substance: colorless powdery substance 2) Solubility : Soluble in methanol and dimethyl sulfoxide, insoluble in chloroform 3) Molecular formula: C57H87N5023 6) Molecular weight: 1 209 (determined by FAB mass spectrometry) 7) Precision mass determined by high decomposition energy FAB mass spectrometry, [M + H] + As indicated below: Measured 値: 1 2 1 0.5 8 6 7 200414902 Calculated 値: 1210.5870 6) Ultraviolet absorption spectrum: Measure the ultraviolet absorption spectrum in methanol, and the maximum absorption expression is as follows: 263nm (ε 9900) 7) Optical rotation Degree: Determine the optical rotation in methanol, as shown below: [a] D29: +1 3.2. (C0.2) 8) Infrared absorption spectrum: The infrared absorption spectrum measured by the potassium bromide (KBr) tablet method is expressed by the maximum absorption shown below: 3383, 2957, 2930, 1738, 1695, 1629, 1464, 1384 ， 1273 ， ll61 1 1 04,1 0 1 4,960cm · 1 9) 1H-NMR spectrum: In heavy dimethanine, the internal standard is measured by heavy dimethanfeng (2.49ppm > 1 Η-nuclear magnetic resonance spectrum:

0.84(6H，t)，0.9 1(3H,d，J = 6.0Hz)，1.2-1.3(8H，m)，1.42(1H 1.57(2H，m)，1.70(lH，m),2.0(7H，m)，2.11(lH，m)52,l7(1H m) 2.26(3H，s),2.3(3H，m)，2.4(3H5m)，2.5-2.6(4H，m)，2,7l(2H d d，J = 6.OHz)，2.80(lH，dd，J = 7.0，12.8Hz)，2.9 1(3H，s)，2 93(1 H br.m)，2.98(lH，dd，J = 2.7，12.8Hz),3.26(lH，t,J = 9.2Hz) 3 36 (3H，s)，3.37(3H，s)，3.4(2H，m)，3.52(lH5m)，3.84(lH,d，J = 8 m z)，3.9(2H，m),3.94(lH5m)，4.14(lH,m)，4.2(2H，m)，4.96(1H d d，J = 2.9,9.5Hz)，5.12(lH,m)，5.30(4H，m)，5.37(2H5m) 5 6 6(1 H，d，J = 8.1Hz),5.90(lH，t，J = 5.9Hz)，5.93(lH，m)，7.82(lH d J = •20- 200414902 8 . lHz)ppm 1 0 ) 13 C -核磁共振光譜： 重二甲亞礪中，內部標準使用重二甲亞碾（39.5ppm)測 定，以下所示爲其13C -核磁共振光譜： 9.4(q)，13.9(q)，19.0(q)，22.0(t)，23.9(t)，24.6(t)，25.2(t)，26. 3(t)，26.6(t)，27· 1(d)，28.7(t)，29.3(t)，29.4(t)，30.9(t),32.9(t)， 36.4(q)，37.8(q)，3 8.8(t)，39.8(t)，39.9(t)，40.2(t)，40.7(t)，4 1. 5(t)，56.6(t)，58.7(q)，60.0(q)，62.3(d)，66.7(d)，69.0(d)，69·9 (d)，70.6(d)，72.7(d)，73 .1(d)，74. l(d)，76.6(d)_77.3(d)，77·4 φ (d)，82.2(d)，83.9(d)，87.5(d)，90.5(d)，101.3(d)，106.7(d)，127. 6(d)，128.2(d)，129.2(d)，129.8(d)，140.5(d)，150.3(s)，163.3 (s)，168.6(s)，169.2(s)，170.1(s)，170.8(s),171.1(s)，171.9(s)， 173.8(s)ppm 1 1)高速液體色層分析法： 管柱· CAPCELLPAK C18UG120,4.6 φχ 150mm (資生堂股 份有限公司製） 溶劑：含有10mM重碳酸銨之40%乙腈水溶液 修 流速：1 .Oml/分鐘 檢出：紫外線吸收260nm 保持時間：1 4.8分鐘 (v) 具有下列物理化學性狀之化合物或其鹽： 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞珮，不溶於氯仿 -21- 200414902 3) 分子式：C55H87N5 02 3 4) 分子量：1 1 8 5 (以F A B質譜法測定） 5) 依高分解能fab質譜法測定之精密質量，[m + H] +如下列 表示： 實測値：1 1 8 6 · 5 8 2 8 計算値：1 1 8 6 · 5 8 7 0 6) 紫外線吸收光譜= 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表示： 263ηχη(ε 1 1000) 7) 旋光度： 於甲醇中測定旋光度，如下列所示値表示： [a ]D29 : +13.9° ( c0.2 ) 8) 紅外線吸收光譜： 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下列所 示之極大吸收表示： 3393,2953,2927,1738,1 695 ,1 632,1466,1384,1273,1 162， 1 1 04,1 0 1 4,960cm·1 9) 1H-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞® ( 2.49ppm)測 定，以下所示爲其1H-核磁共振光譜： 0.83(6H，t，J = 6.6Hz)，0.84(3H，t，J = 7.3Hz)，0.92(3H，d，J = 6.2H z),1.12(2H，dt，J = 6.6Hz)，l，2-1.3(12H，m)，1.4-1.5(2H，m)，1.5 5(2H，m)，1.70(lH，m)，2.0(3H，m)，2.11(lH，m)52.17(lH，m)，2.2 6(3H，s)，2.3(3H，m)，2.4-2.5(3H，m)，2.5-2.6(3H，m)，2.79(lH， 200414902 dd，卜6.6，12.8Hz)，2.9 1(3H，s)，2.94(lH，br.m)，2.99(lH，dd，J = 2.8，l2.8Hz)，3.27(lH，t，J = 9.3Hz)，3.36(3H，s)，3.37(3H，s)，3. 40(2H，m)，3,52(lH，m)，3.84(lH，d，J = 8.8Hz)，3.87(2H，m)，3.9 4(1H，m)，4.13(lH，m)，4.19(2H，m)，4.96(lH5dd，：n9,9.2HZ)， 5*11(lH5m)?5.37(2H?m)55.37(2H?m)?5.66(lH?d?J = 8.1Hz)55. 90(lH，t，J = 5.5Hz)，5.93(lH，m)，7.83(lH，d，J = 8.1Hz)ppm 1 0) 13 C -核磁共振光譜： 重二甲亞®中，內部標準使用重二甲亞碾（39.5ppm)測 定’以下所示爲其13C -核磁共振光譜： _ 9.5(q)，19.0(q)，22.5(q)，23.9(t)，24.5(t)，26.8(t)，27.1(d)，27· 4(d)，28.7(t),28.9(d)，28.9(d)，29.3(t)，29.3(t),29.5(t)，33.2 (t)，36.4(q)，37.8(q)，3 8.5(t)，3 8.8(t)，39.8(t)，39.9(t)，40.1(t)， 40.2(t)，4 1.5(t)，56.6(t)，58.7(q)，60.0(q)，62.3(d)，67.3(d)，69. l(d)，70,〇(d)，70.6(d)，72.7(d)，73.1(d)，74.1(d)，76.6(d)，77.2 (d)，77.5(d)，82.2(d)，83.9(d)，87.6(d)，90.5(d)，101 .3(d)，106. 6 ⑷，140.5(d)，150.3(s)，163.3(s)，168.5(s)，169.3(s)，170.1 (s)，170.8(s)，171.1(s)，172.0(s)，173.8(s)ppm · 11)局速液體色層分析法： 管柱：CAPCELLPAK C18UG120,4.6(/)X 1 5 0mm (資生堂股 份有限公司製） 溶劑：含有10mM重碳酸銨之42%乙腈水溶液 流速：1 .Oml/分鐘 檢出·紫外線吸收2 6 0 n m 保持時間：9.5分鐘 -23- 200414902 (Vi) 具有下列物理化學性狀之化合物或其鹽： 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞碾，不溶於氯仿 3) 分子式· C56H87N5023 6) 分子量：1197(以FAB質譜法測定） 7) 依高分解能FAB質譜法測定之精密質量，[M + H] +如下列 表示： 實測値：1 1 9 8 · 5 8 7 5 # 計算値：1 1 9 8 · 5 8 7 0 6) 紫外線吸收光譜： 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表示： 263 nm( ε 8 7 0 0) 7) 旋光度： 於甲醇中測定旋光度，如下列所示値表示·· [a]D29: — 6.8 ( c 0.2 ) 8) 紅外線吸收光譜： · 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下列所 示之極大吸收表示： 3414，2928，2856,1738,1689,1632,1465,1394,1273，1161 1 1 26,1 1 04,1 0 1 4,959cm1 9) iH-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞® ( 2.49Ppm)測 定，以下所示爲其1H-核磁共振光譜： •24- 200414902 0·84(6Η，t),0.92(3H，d，J = 6.2Hz)，1，2-1.3(1 2H，m)5 1.42(1 Η, m)，1.57(2H，m)，1.71(lH,m)，2.0(7H，m)，2.11(lH，m)，2.17(lH， m)，2.25(3H，s)，2.3(3H，m)，2.41(lH，m)，2.43(2H，m)，2.6(4H， m)，2.80(lH，dd，J = 6.6，13.6Hz)，2.91(3H，s)，2.93(lH，m)，2.98 (lH，dd，3.3，13.6Hz)，3.27(lH，t，J = 9.5Hz)，3.36(3H，s)，3.37(3 H，s)，3.4(2H，m)，3.5 2(lH，m)，3.84(lH，d，J = 8.4Hz)，3.87(2H， m)，3.94(lH，m)54.13(lH，m)，4.19(2H，m)54.96(lH，dd，J = 3.3,9. 5Hz)，5.90(lH，t，J = 5.9Hz)，5.37(2H，m)，5.66(lH，d，J = 8.1Hz)， 5.90(lH，t，J = 5.9Hz)，5.93(lH，m)，7.8 3(lH，d，J = 8.1Hz)ppm · 10) 13c-核磁共振光譜： 重二甲亞楓中，內部標準使用重二甲亞碾（39.5ppm)測 定，以下所示爲其13C -核磁共振光譜： 9.5(q)，1 4.0(q)，1 9.0(q)，22. l(q)，23.9(t)，24.8(t)，26.3( t)，26. 6(q)，27.1(d)，28.6(t)，28.6(t)，29.0(t)，29.1(t)，29.3(t)，3 1.3 (t)，32.9(t)，3 6.4(q)，3 7.8(q)，38.9(t)，39.8(t)，39.9(t)，40.2 (t)，40.7(t)，4 1.5(t)，56.6(t)，5 8.7(q)，60.0(q)，62.3(d)，66.7 (d)，69.0(d)，69.9(d)，70.5(d)，72.7(d)，73.2(d)，74· 1(d)，76.6 籲 (d)，77.2(d)，77.5(d)，82.2(d)，83.9(d)，89.1(d)，90.5 (d)，10 1. 3(d)，106.6(d)，129.1(d)，130.1(d)，140.6(d)，150.3(s)，163.3 (s)，168.4(s)，169.2(s)，170.1(s)，170.8(s)，171.1(s)，172.0(s)， 173.8(s)ppm 1 1)高速液體色層分析法： 管柱：CAPCELLPAK C18UG12 0,4.6(/)x 1 5 0mm (資生堂股 份有限公司製） -25- 200414902 溶劑：含有10mM重碳酸銨之42%乙腈水溶液 流速.1. 〇 ιώ 1 /分鐘 檢出：紫外線吸收2 6 0 n m 保持時間：1 〇 . 2分鐘 (vii ) 具有下列物理化學性狀之化合物或其鹽： 1 )物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞楓，不溶於氯仿 3) 分子式：C55H87N5 02 3 4) 分子量：1185(以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[M + H] +如下列 表示： 實測値：1 1 8 6.5 9 1 2 計算値：1186.5870 6) 紫外線吸收光譜： 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表示： 2 63 nm( ε 3600) 7) 旋光度： 於甲醇中測定旋光度，如下列所示値表示： [a]D29: + 4.3。（c0.5) 8 )紅外線吸收光譜： 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下列 所示之極大吸收表示： 3371，2926,2855,1 738,1691 ,1628, 1466.1384,1273,1 161， -26- 200414902 1 1 04,1 0 1 6,962cm-1 9) iH-核磁共振光譜： 重二甲亞楓中，內部標準使用重二甲亞碾（2.05ppm )測 定，以下所示爲其1 Η -核磁共振光譜： 0.84(6H，t)，0.92(3H，d，J = 5.5Hz)，1.2-1 .3(1 8H，m)，1.42(lH， m)，1.5 5(2H，m)，1.70(lH5m)，2.0(3H，m)52.14(2H，m)，2.26(3H， s)，2.3(3H，m)，2.4 1(lH，m)，2.47(2H，m)，2.6(4H，m)，2.80(lH，d d，J = 6,2，13.6Hz)，2.92(3H，s)，2.94(lH，br.m),3.0 1(lH.dd，J = 2. 2，13.6Hz)，3.27(lH，t，J = 8.8H2)，3.36(3H，5)，3.37(3H，5)，3.40 (2H,m)，3.53(1 H，m)，3.86(lH，d，J = 9.5Hz)，3.9(3H，m)，4· 13(1 H，m)，4.19(2H，m)，4.96(lH，dd，J= 1.859.2Hz),5.11(lH，m),5.3 7(2H，m)，5.65(lH，d，J = 7.7Hz)，5.90(lH，t，J = 5.0Hz)，5.93(lH， m)，7.8 1 (lH，d，J = 7.7Hz)ppm 10) 13c-核磁共振光譜： 重二甲亞楓中，內部標準使用重二甲亞碾（39.5ppm )測 定，以下所示爲其13C -核磁共振光譜： 9.5(q)，14.0(q)，19.0(q)，22.1(t)，23.9(t)，24.5(t),27.2(d)，28. 7(t)52 8.7 (0)，2 8.9(t)，2 8.9(t)，2 9.0(t)，29.0(t)，29.1(d).3 1.3 (t)，3 3.3(t),3 6.4(q)，3 7.8(q)，3 8.8(t)，3 9.8(t)，39.9(t)，40.2(t)， > 40.7(t)，4 1.5(t)，56.S(t)，5 8.7(q),60.0(q)，62.4(d)，66.5(d)，69. 0(d)，70.6(d)，72.7(d),72.9(d)，74.1(d)，76.6(d)，77.3(d)，77.5 (d)，82.0(d),84.0(d)，87.3(d)，90.4(d)，101.3(d)，106.9(d)，140. 5(d)，150.2(s)，163.3(s)，168.7(s)，169.3(s)，170.1(s)，170.6 (s)，171.1(s),171.8(s)，173.5(s)ppm -27· 200414902 1 1)高速液體色層分析法： 管柱：CAPCELLPAK C18UG120,4.6 p X 1 50mm (資生堂股 份有限公司製） 溶劑：含有1 〇 m Μ重碳酸銨之4 2 %乙腈水溶液 流速：1.0ml/分鐘 檢出：紫外線吸收260nm 保持時間：1 1 .2分鐘 (viii) 具有下列物理化學性狀之化合物或其鹽： 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於水，不溶於氯仿 3) 分子式： 4) 分子量：5 43 (以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[M + H] +如下列 表示： 實測値·· 544.2240 計算値：5 4 4 · 2 2 5 5 6) 紫外線吸收光譜： 於水中測定紫外光吸收光譜，如下所示極大吸收表示： 263nm(ε 8700) 7) 旋光度： 於水中測定旋光度，如下列所示値表示： [a ]D29 : + 6 2.7 0 ( c0.2) 8 )紅外線吸收光譜： 200414902 以溴化鉀（K B r )錠劑法測定之紅外線吸收光譜以下列 所示之極大吸收表示： 3393,2929,1688, 1 620. 1468,1394,12 7 4.1094,1065,1019， 962cm -1 9) iH-核磁共振光譜： 重水中，內部標準使用重水（4.75Ppm)測定，以下所示 爲其1H-核磁共振光譜： 2.2 1(lH，ddd，J = 3.3,5.9，14.7Hz)，2.3-2.4(3H，m)，2.44(3H，s)， 2.86(lH，dd，J = 9.2，13.6Hz)，2.97(lH，d，J = 14.7Hz)，3.07(3H， s)，3.13(lH，d，J=14.7Hz)，3.24(lH，dd，J = 4.4，l 3.6Hz)，3.80(1 H，d，J = 9.9Hz)，3.93(lH，d，J = 6.6Hz)，4.20(lH，d，J = 5.1Hz)，4.2 5(lH，dt，J = 7.0Hz)，4.3 8(lH，m)，4.4 1(lH，d，J = 9.9Hz)，4.44(lH， m)，5.56(lH，dd，J = 3.3,5.9Hz)，5.8 1(lH，d，J = 8.1Hz)，6.00(lH，t， J = 5.5Hz)，7.74(lH，d，J = 8.1Hz)ppm 10) 13c-核磁共振光譜： 重水中，內部標準使用二噚烷（66.5 ppm)測定，以下所 示爲其13C -核磁共振光譜： 36.4(q)，38.6( q)，38.7(t)，40· l(t)，40.4(t)，58.6(t)，63.1(d),68. 7(d)，69.1(d)，69.4(d)，71.8(d)，76.9(d),81.6(d)，85.0(d)，85.3 (d)，101.3(d)，109.0(d)，142.2(d)，151.4(5)，166.5(5)，172.3(5 )?173.5(5)ppm 11) 高速液體色層分析法： 管柱：CAPCELLPAK C18UG12O,4.60x 150mm (資生堂股 份有限公司製） -29- 200414902 溶劑：10mM重碳酸銨 流速：1.0ml/分鐘 檢出：紫外線吸收2 60nm 保持時間：9 · 2分鐘 (iX) 具有下列物理化學性狀之化合物或其鹽： 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞碾，不溶於氯仿 3) 分子式：C22H31N5O10 4) 分子量：5 25 (以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[m + H] +如下列 表示： 實測値：5 2 6 · 2 1 5 3 計算値：5 2 6.9 1 4 9 6) 紫外線吸收光譜： 於水中測定紫外光吸收光譜，如下所示極大吸收表示： 260nm( ε 8700) 7) 旋光度： 於水中測定旋光度，如下列所示値表示： [a ]D 2 9 : + 6 5.5 ° ( c0.2 ) 8) 紅外線吸收光譜： 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下列 所示之極大吸收表示： 3403,2953,1690,1633,1467,1382,1361,1274,1098,1067, -30- 200414902 1 0 1 3.9 64cm·1 9) 1H-核磁共振光譜： 重水中，內部標準使用重水（4.7 5 ppm)測定，以下所示 爲其1H-核磁共振光譜： 2.2-2.4(4H，m)，2.43(3H，s)，2.86(lH，dd，J = 9.9，13.6Hz)，2.92 (lH，dd，J = 6.6，12.7Hz)，2.97(3H，s)，3.23(lH，dd，J = 4.0，13.6H z)，3·32(1Η，dd，J = 7.3, 12.7Hz)，3.87(1 H，d，J = 9.5Hz)，4.08(1 Η， m)，4.18(lH，m)，4.3 1(lH，dt，J = 5.8Hz)，4.35(lH，m)，4.3 8(lH， m)，5.56(1 H，dd，J = 2.6，5·9Ηζ)，5.80(1 H，d，J = 8.1 Hz)，6.06(1 H， t，J = 5.9Hz),6.47( lH，dd，J = 6.6,7.3Hz)，7.64(lH，d，J = 8.1Hz)p pm 10) 13c-核磁共振光譜： 重水中，內部標準使用二噚烷（66.5ppm)測定，以下所 示爲其13C -核磁共振光譜： 32.7(q),3 8.6(t)，40.0(q)，40.5(t)，40.9(t)，5 1.0(t)，63.2(d)，69. 8(d)，71.7(d)，76.7(d)，82.4(d)，85.2(d)，85.6(d)，101.8(d), 107. 7(d)，123.1(d)，141.4(d)，144.2(s)，152.4(s)，167.7(s)，168.6(s )，171.0(s)ppm 11) 高速液體色層分析法： 管柱：CAPCELLPAK C18UG120,4.6 0 X 1 5 0mm (資生堂股 份有限公司製） 溶劑：含有10mM重碳酸銨之3%乙腈水溶液 流速：1 · 0 m 1 /分鐘 檢出：紫外線吸收2 60nm -31- 200414902 保持時間：13 ·0分鐘 具有下列物理化學性狀之化合物或其鹽 1)物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞礙，不溶於氯仿 3) 分子式· C42H67N5016 4) 分子量：8 9 7(以FAB質譜法測定） [Μ + ΗΓ如下列0.84 (6H, t), 0.9 1 (3H, d, J = 6.0Hz), 1.2-1.3 (8H, m), 1.42 (1H 1.57 (2H, m), 1.70 (lH, m), 2.0 (7H, m), 2.11 (lH, m) 52, l7 (1H m) 2.26 (3H, s), 2.3 (3H, m), 2.4 (3H5m), 2.5-2.6 (4H, m), 2,7l (2H dd , J = 6.0 Hz), 2.80 (lH, dd, J = 7.0, 12.8 Hz), 2.9 1 (3H, s), 2 93 (1 H br.m), 2.98 (lH, dd, J = 2.7, 12.8 Hz), 3.26 (lH, t, J = 9.2 Hz) 3 36 (3H, s), 3.37 (3H, s), 3.4 (2H, m), 3.52 (lH5m), 3.84 (lH, d, J = 8 mz), 3.9 (2H, m), 3.94 (lH5m), 4.14 (lH, m), 4.2 (2H, m), 4.96 (1H dd, J = 2.9, 9.5Hz), 5.12 (lH, m), 5.30 (4H, m), 5.37 (2H5m) 5 6 6 (1 H, d, J = 8.1Hz), 5.90 (lH, t, J = 5.9Hz), 5.93 (lH, m), 7.82 (lH d J = • 20- 200414902 8. LHz) ppm 1 0) 13 C-NMR spectrum: In heavy dimethanine, the internal standard is measured using heavy dimethanine (39.5ppm), which is shown below as its 13C-NMR Spectrum: 9.4 (q), 13.9 (q), 19.0 (q), 22.0 (t), 23.9 (t), 24.6 (t), 25.2 (t), 26.3 (t), 26.6 (t), 27 · 1 (d), 28.7 (t), 29.3 (t), 29.4 (t), 30.9 (t), 32.9 (t), 36.4 (q), 37.8 (q), 3 8.8 (t), 39.8 (t ), 39.9 (t), 40.2 (t), 40.7 (t), 4 1. 5 (t), 56.6 (t), 58.7 (q), 60.0 (q), 62.3 (d), 66.7 (d), 69.0 (d), 69 · 9 (d), 70.6 (d), 72.7 (d), 73.1 (d), 74.1 (d), 76.6 (d) _77.3 (d), 77 · 4 φ (d), 82.2 (d), 83.9 (d), 87.5 (d), 90.5 (d), 101.3 (d), 106.7 (d), 127.6 (d), 128.2 (d), 129.2 (d ), 129.8 (d), 140.5 (d), 150.3 (s), 163.3 (s), 168.6 (s), 169.2 (s), 170.1 (s), 170.8 (s), 171.1 (s), 171.9 (s ), 173.8 (s) ppm 1 1) High-speed liquid chromatography analysis method: column · CAPCELLPAK C18UG120, 4.6 χ 150mm (made by Shiseido Co., Ltd.) Solvent: 40% acetonitrile aqueous solution containing 10mM ammonium bicarbonate Repair flow rate: 1. Oml / minute detection: UV absorption at 260nm Holding time: 1 4.8 minutes (v) Compound or salt thereof having the following physical and chemical properties: 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, Formaridine, insoluble in chloroform-21- 200414902 3) Molecular formula: C55H87N5 02 3 4) Molecular weight: 1 1 8 5 (determined by FAB mass spectrometry) 5) Precision mass determined by high resolution energy fab mass spectrometry, [m + H ] + List below Indication: Measured radon: 1 1 8 6 · 5 8 2 8 Calculated radon: 1 1 8 6 · 5 8 7 0 6) Ultraviolet absorption spectrum = The ultraviolet absorption spectrum is measured in methanol, and the maximum absorption is shown as follows: 263ηχη ( ε 1 1000) 7) Optical rotation: Measure the optical rotation in methanol as shown below: [a] D29: + 13.9 ° (c0.2) 8) Infrared absorption spectrum: Take potassium bromide (KBr) ingot The infrared absorption spectrum measured by the agent method is expressed by the maximum absorption shown below: 3393,2953,2927,1738,1 695, 1 632,1466,1384,1273,1 162, 1 1 04,1 0 1 4,960cm · 1 9) 1H-NMR spectrum: In heavy dimethanine, the internal standard is determined using heavy dimethan® (2.49ppm), and its 1H-NMR spectrum is shown below: 0.83 (6H, t, J = 6.6Hz ), 0.84 (3H, t, J = 7.3Hz), 0.92 (3H, d, J = 6.2H z), 1.12 (2H, dt, J = 6.6Hz), 1, 2-1.3 (12H, m), 1.4-1.5 (2H, m), 1.5 5 (2H, m), 1.70 (lH, m), 2.0 (3H, m), 2.11 (lH, m) 52.17 (lH, m), 2.2 6 (3H, s ), 2.3 (3H, m), 2.4-2.5 (3H, m), 2.5-2.6 (3H, m), 2.79 (lH, 200414902 dd, Bu 6.6, 12.8Hz), 2.9 1 (3H, s), 2.94 (l H, br.m), 2.99 (lH, dd, J = 2.8, l2.8 Hz), 3.27 (lH, t, J = 9.3 Hz), 3.36 (3H, s), 3.37 (3H, s), 3. 40 (2H, m), 3, 52 (lH, m), 3.84 (lH, d, J = 8.8Hz), 3.87 (2H, m), 3.9 4 (1H, m), 4.13 (lH, m), 4.19 (2H, m), 4.96 (lH5dd,: n9,9.2HZ), 5 * 11 (lH5m)? 5.37 (2H? M) 55.37 (2H? M)? 5.66 (lH? D? J = 8.1Hz) 55 90 (lH, t, J = 5.5 Hz), 5.93 (lH, m), 7.83 (lH, d, J = 8.1 Hz) ppm 1 0) 13 C-Nuclear magnetic resonance spectroscopy: heavy dimethene®, internal The standard uses heavy dimethanine (39.5ppm) to measure '13C-NMR spectrum as shown below: 9.5 (q), 19.0 (q), 22.5 (q), 23.9 (t), 24.5 (t), 26.8 (t), 27.1 (d), 27.4 (d), 28.7 (t), 28.9 (d), 28.9 (d), 29.3 (t), 29.3 (t), 29.5 (t), 33.2 (t ), 36.4 (q), 37.8 (q), 3 8.5 (t), 3 8.8 (t), 39.8 (t), 39.9 (t), 40.1 (t), 40.2 (t), 4 1.5 (t), 56.6 (t), 58.7 (q), 60.0 (q), 62.3 (d), 67.3 (d), 69.1 (d), 70, 〇 (d), 70.6 (d), 72.7 (d), 73.1 (d), 74.1 (d), 76.6 (d), 77.2 (d), 77.5 (d), 82.2 (d), 83.9 (d), 87.6 (d), 90.5 (d), 101.3 (d) , 106. 6 ⑷, 140.5 (d), 150.3 (s ), 163.3 (s), 168.5 (s), 169.3 (s), 170.1 (s), 170.8 (s), 171.1 (s), 172.0 (s), 173.8 (s) ppm Analytical method: Column: CAPCELLPAK C18UG120, 4.6 (/) X 1 50mm (manufactured by Shiseido Co., Ltd.) Solvent: 42% acetonitrile aqueous solution containing 10mM ammonium bicarbonate Flow rate: 1.0 ml / min detection · UV absorption 2 6 0 nm retention time: 9.5 minutes-23- 200414902 (Vi) Compounds or salts thereof having the following physical and chemical properties: 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethyl arylene, Insoluble in chloroform 3) Molecular formula · C56H87N5023 6) Molecular weight: 1197 (determined by FAB mass spectrometry) 7) Precision mass determined by high decomposition energy FAB mass spectrometry, [M + H] + as shown below: Actual measurement: 1 1 9 8 · 5 8 7 5 # Calculation 値: 1 1 9 8 · 5 8 7 0 6) Ultraviolet absorption spectrum: The ultraviolet absorption spectrum is measured in methanol, and the maximum absorption is expressed as follows: 263 nm (ε 8 7 0 0) 7 ) Optical rotation: Measure the optical rotation in methanol as shown below: [a] D29: — 6.8 (c 0.2) 8) Infrared absorption spectrum: · The infrared absorption spectrum measured by potassium bromide (KBr) lozenge method is expressed by the maximum absorption shown below: 3414, 2928, 2856, 1738, 1689, 1632, 1465, 1394, 1273, 1161 1 1 26,1 1 04,1 0 1 4,959cm1 9) iH-NMR spectrum: In heavy dimethanine, the internal standard is determined using heavy dimethan® (2.49Ppm), and its 1H-NMR spectrum is shown below: • 24- 200414902 0.84 (6Η, t), 0.92 (3H, d, J = 6.2Hz), 1, 2-1.3 (1 2H, m) 5 1.42 (1 Η, m), 1.57 (2H, m), 1.71 (lH, m), 2.0 (7H, m), 2.11 (lH, m), 2.17 (lH, m), 2.25 (3H, s), 2.3 (3H, m), 2.41 (lH, m), 2.43 ( 2H, m), 2.6 (4H, m), 2.80 (lH, dd, J = 6.6, 13.6 Hz), 2.91 (3H, s), 2.93 (lH, m), 2.98 (lH, dd, 3.3, 13.6 Hz ), 3.27 (lH, t, J = 9.5 Hz), 3.36 (3H, s), 3.37 (3 H, s), 3.4 (2H, m), 3.5 2 (lH, m), 3.84 (lH, d, J = 8.4 Hz), 3.87 (2H, m), 3.94 (lH, m) 54.13 (lH, m), 4.19 (2H, m) 54.96 (lH, dd, J = 3.3, 9.5 Hz), 5.90 (lH , T, J = 5.9 Hz), 5.37 (2H, m), 5.66 (lH, d, J = 8.1 Hz), 5.90 (lH, t, J = 5.9 Hz), 5.93 (lH, m), 7.8 3 ( lH d, J = 8.1Hz) ppm · 10) 13c-NMR spectrum: In heavy dimethanine, the internal standard is measured using heavy dimethanine (39.5ppm), and its 13C-NMR spectrum is shown below: 9.5 (q), 1 4.0 (q), 1 9.0 (q), 22. l (q), 23.9 (t), 24.8 (t), 26.3 (t), 26.6 (q), 27.1 (d), 28.6 (t), 28.6 (t), 29.0 (t), 29.1 (t), 29.3 (t), 3 1.3 (t), 32.9 (t), 3 6.4 (q), 3 7.8 (q), 38.9 ( t), 39.8 (t), 39.9 (t), 40.2 (t), 40.7 (t), 4 1.5 (t), 56.6 (t), 5 8.7 (q), 60.0 (q), 62.3 (d), 66.7 (d), 69.0 (d), 69.9 (d), 70.5 (d), 72.7 (d), 73.2 (d), 74.1 (d), 76.6 (d), 77.2 (d), 77.5 ( d), 82.2 (d), 83.9 (d), 89.1 (d), 90.5 (d), 10 1.3 (d), 106.6 (d), 129.1 (d), 130.1 (d), 140.6 (d) , 150.3 (s), 163.3 (s), 168.4 (s), 169.2 (s), 170.1 (s), 170.8 (s), 171.1 (s), 172.0 (s), 173.8 (s) ppm 1 1) High speed Liquid chromatography analysis method: Column: CAPCELLPAK C18UG12 0,4.6 (/) x 1 50mm (made by Shiseido Co., Ltd.) -25- 200414902 Solvent: 42% acetonitrile aqueous solution containing 10mM ammonium bicarbonate. Flow rate. 1. 〇ιώ 1 / minute detection: UV Linear absorption 2 60 nm Holding time: 1 0.2 minutes (vii) Compound or salt having the following physicochemical properties: 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol and dimethyl Yafeng, insoluble in chloroform 3) Molecular formula: C55H87N5 02 3 4) Molecular weight: 1185 (determined by FAB mass spectrometry) 5) Precision mass determined by high decomposition energy FAB mass spectrometry, [M + H] + as shown below: Measured 値: 1 1 8 6.5 9 1 2 Calculated 値: 1186.5870 6) Ultraviolet absorption spectrum: The ultraviolet absorption spectrum is measured in methanol, and the maximum absorption is expressed as follows: 2 63 nm (ε 3600) 7) Optical rotation: measured in methanol Optical rotation, as shown below: [a] D29: + 4.3. (C0.5) 8) Infrared absorption spectrum: The infrared absorption spectrum measured by the potassium bromide (KBr) lozenge method is expressed by the maximum absorption shown below: 3371, 2926, 2855, 1 738, 1691, 1628, 1466.1384, 1273,1 161, -26- 200414902 1 1 04,1 0 1 6,962cm-1 9) iH-NMR spectrum: In heavy dimethanine, the internal standard is determined using heavy dimethanine (2.05ppm), the following Shown for its 1 Η-NMR spectrum: 0.84 (6H, t), 0.92 (3H, d, J = 5.5Hz), 1.2-1.3 (18H, m), 1.42 (lH, m), 1.5 5 (2H, m), 1.70 (lH5m), 2.0 (3H, m) 52.14 (2H, m), 2.26 (3H, s), 2.3 (3H, m), 2.4 1 (lH, m), 2.47 (2H , M), 2.6 (4H, m), 2.80 (lH, dd, J = 6,2, 13.6 Hz), 2.92 (3H, s), 2.94 (lH, br.m), 3.0 1 (lH.dd, J = 2.2, 13.6 Hz), 3.27 (lH, t, J = 8.8H2), 3.36 (3H, 5), 3.37 (3H, 5), 3.40 (2H, m), 3.53 (1 H, m) , 3.86 (lH, d, J = 9.5Hz), 3.9 (3H, m), 4.13 (1 H, m), 4.19 (2H, m), 4.96 (lH, dd, J = 1.859.2Hz), 5.11 (lH, m), 5.3 7 (2H, m), 5.65 (lH, d, J = 7.7Hz), 5.90 (lH, t, J = 5.0Hz), 5.93 (lH, m), 7.8 1 (lH , D J = 7.7Hz) ppm 10) 13c-NMR spectrum: In heavy dimethylformate, the internal standard is determined using heavy dimethylformite (39.5ppm), and its 13C-NMR spectrum is shown below: 9.5 (q) , 14.0 (q), 19.0 (q), 22.1 (t), 23.9 (t), 24.5 (t), 27.2 (d), 28.7 (t) 52 8.7 (0), 2 8.9 (t), 2 8.9 (t), 2 9.0 (t), 29.0 (t), 29.1 (d). 3 1.3 (t), 3 3.3 (t), 3 6.4 (q), 3 7.8 (q), 3 8.8 (t) , 3 9.8 (t), 39.9 (t), 40.2 (t), > 40.7 (t), 4 1.5 (t), 56.S (t), 5 8.7 (q), 60.0 (q), 62.4 ( d), 66.5 (d), 69.0 (d), 70.6 (d), 72.7 (d), 72.9 (d), 74.1 (d), 76.6 (d), 77.3 (d), 77.5 (d), 82.0 (d), 84.0 (d), 87.3 (d), 90.4 (d), 101.3 (d), 106.9 (d), 140. 5 (d), 150.2 (s), 163.3 (s), 168.7 (s ), 169.3 (s), 170.1 (s), 170.6 (s), 171.1 (s), 171.8 (s), 173.5 (s) ppm -27 · 200414902 1 1) High-speed liquid chromatography analysis method: Column: CAPCELLPAK C18UG120, 4.6 p X 1 50mm (manufactured by Shiseido Co., Ltd.) Solvent: 4 2% acetonitrile aqueous solution containing 10 mM ammonium bicarbonate Flow rate: 1.0 ml / min Detection: UV absorption at 260 nm Hold time: 1 1.2 minutes (viii) with Compounds or their salts with the following physical and chemical properties: 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in water, insoluble in chloroform 3) Molecular formula: 4) Molecular weight: 5 43 (determined by FAB mass spectrometry) 5) The precise mass measured by high resolution energy FAB mass spectrometry, [M + H] + is as follows: Measured 値 ·· 544.2240 Calculated 値: 5 4 4 · 2 2 5 5 6) Ultraviolet absorption spectrum: Determine ultraviolet light in water The absorption spectrum is shown by the maximum absorption as shown below: 263nm (ε 8700) 7) Optical rotation: Measure the optical rotation in water as shown below: [a] D29: + 6 2.7 0 (c0.2) 8) Infrared Absorption spectrum: 200414902 The infrared absorption spectrum measured by the potassium bromide (KB r) tablet method is expressed by the maximum absorption shown below: 3393, 2929, 1688, 1 620. 1468, 1394, 12 7 4.1094, 1065, 1019, 962cm -1 9) iH-NMR spectrum: In heavy water, the internal standard is measured using heavy water (4.75Ppm), and its 1H-NMR spectrum is shown below: 2.2 1 (lH, ddd, J = 3.3, 5.9, 14.7 Hz ), 2.3-2.4 (3H, m), 2.44 (3H, s), 2.86 (lH, dd, J = 9.2, 13.6 Hz), 2.9 7 (lH, d, J = 14.7Hz), 3.07 (3H, s), 3.13 (lH, d, J = 14.7Hz), 3.24 (lH, dd, J = 4.4, l 3.6Hz), 3.80 (1 H , D, J = 9.9 Hz), 3.93 (lH, d, J = 6.6 Hz), 4.20 (lH, d, J = 5.1 Hz), 4.2 5 (lH, dt, J = 7.0 Hz), 4.3 8 (lH , M), 4.4 1 (lH, d, J = 9.9 Hz), 4.44 (lH, m), 5.56 (lH, dd, J = 3.3, 5.9 Hz), 5.8 1 (lH, d, J = 8.1 Hz) , 6.00 (lH, t, J = 5.5Hz), 7.74 (lH, d, J = 8.1Hz) ppm 10) 13c-NMR spectrum: In heavy water, the internal standard was measured using dioxane (66.5 ppm), as shown below Shown as its 13C-NMR spectrum: 36.4 (q), 38.6 (q), 38.7 (t), 40 · l (t), 40.4 (t), 58.6 (t), 63.1 (d), 68.7 ( d), 69.1 (d), 69.4 (d), 71.8 (d), 76.9 (d), 81.6 (d), 85.0 (d), 85.3 (d), 101.3 (d), 109.0 (d), 142.2 ( d), 151.4 (5), 166.5 (5), 172.3 (5)? 173.5 (5) ppm 11) High-speed liquid chromatography analysis method: Column: CAPCELLPAK C18UG12O, 4.60x 150mm (made by Shiseido Co., Ltd.) -29 -200414902 Solvent: 10mM ammonium bicarbonate Flow rate: 1.0ml / min Detection: UV absorption 2 60nm Hold time: 9 · 2 minutes (iX) List of physical or chemical properties of compounds or their salts: 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethyl arylene, insoluble in chloroform 3) Molecular formula: C22H31N5O10 4) Molecular weight: 5 25 ( (Measured by FAB mass spectrometry) 5) The precise mass measured by high decomposition energy FAB mass spectrometry, [m + H] + is as follows: Measured 値: 5 2 6 · 2 1 5 3 Calculated 値: 5 2 6.9 1 4 9 6 ) Ultraviolet absorption spectrum: The ultraviolet absorption spectrum is measured in water, and the maximum absorption is shown as follows: 260nm (ε 8700) 7) Optical rotation: The optical rotation is measured in water, as shown below: [a] D 2 9: + 6 5.5 ° (c0.2) 8) Infrared absorption spectrum: The infrared absorption spectrum measured by the potassium bromide (KBr) tablet method is expressed by the maximum absorption shown below: 3403, 2953, 1690, 1633, 1467, 1382 , 1361,1274,1098,1067, -30- 200414902 1 0 1 3.9 64cm · 1 9) 1H-NMR spectrum: In heavy water, the internal standard is measured using heavy water (4.7 5 ppm), and its 1H-NMR is shown below Resonance spectrum: 2.2-2.4 (4H, m), 2.43 (3H, s), 2.86 (lH, dd, J = 9.9, 13.6Hz), 2.92 (lH, dd, J = 6.6, 12.7Hz), 2.97 (3H, s), 3.23 (lH, dd, J = 4.0, 13.6Hz), 3.32 (1Η, dd, J = 7.3, 12.7Hz) , 3.87 (1 H, d, J = 9.5 Hz), 4.08 (1 Η, m), 4.18 (lH, m), 4.3 1 (lH, dt, J = 5.8 Hz), 4.35 (lH, m), 4.3 8 (lH, m), 5.56 (1 H, dd, J = 2.6, 5.9Ηζ), 5.80 (1 H, d, J = 8.1 Hz), 6.06 (1 H, t, J = 5.9 Hz), 6.47 (lH, dd, J = 6.6, 7.3 Hz), 7.64 (lH, d, J = 8.1 Hz) p pm 10) 13c-NMR spectrum: In heavy water, the internal standard was measured using dioxane (66.5ppm), the following The 13C-NMR spectra are shown: 32.7 (q), 3 8.6 (t), 40.0 (q), 40.5 (t), 40.9 (t), 5 1.0 (t), 63.2 (d), 69.8 (d), 71.7 (d), 76.7 (d), 82.4 (d), 85.2 (d), 85.6 (d), 101.8 (d), 107.7 (d), 123.1 (d), 141.4 (d) , 144.2 (s), 152.4 (s), 167.7 (s), 168.6 (s), 171.0 (s) ppm 11) High-speed liquid chromatography analysis method: Tube column: CAPCELLPAK C18UG120, 4.6 0 X 1 5 0mm (Shiseido shares Co., Ltd.) Solvent: 3% acetonitrile aqueous solution containing 10 mM ammonium bicarbonate Flow rate: 1.0 m / min Detection: UV absorption 2 60nm -31- 2004 14902 Retention time: 13 · 0 minutes Compounds or salts thereof having the following physical and chemical properties 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethylamine, and insoluble in chloroform 3) Molecular formula · C42H67N5016 4) Molecular weight: 8 9 7 (determined by FAB mass spectrometry) [M + ΗΓ is as follows

5)依高分解能FAB質譜法測定之精密質量 表示： 實測値：8 9 8 · 4 6 6 9 計算値：8 9 8 · 4 6 6 1 6)紫外線吸收光譜： 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表示 263nm( £ 7500) 7) 旋光度： 於甲醇中測定旋光度’如下列所示値表示：5) Precision mass expression determined by high resolution energy FAB mass spectrometry: Measured 値: 8 9 8 · 4 6 6 9 Calculated 値: 8 9 8 · 4 6 6 1 6) Ultraviolet absorption spectrum: Measure the ultraviolet light absorption spectrum in methanol As shown below, the maximum absorption indicates 263nm (£ 7500) 7) Optical rotation: The optical rotation measured in methanol is shown as follows:

[a ]D29 : + 19.8 ° ( c0.2) 8) 紅外線吸收光譜= 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下列 所示之極大吸收表示： 3394，2926，2855，1737，1691，1629,1467,1397,1274,1203， 1 131,1 094,1 0 1 3,962cm·1 9) 1H-核磁共振光譜： 重二甲亞楓中，內部標準使用重二甲亞碾（2.49ppm )測 、32- 200414902 定，以下所示爲其1Η-核磁共振光譜： 0.84(3H，t，J = 7.1Hz)，0.88(3H，d，J = 6.3Hz)，1.2-1.3(18H，m)，l. 57(2H，m)，1.9-2.2(8H，m)，2.24(3H，s)52.43 (lH，dd，J = 5.5-15. lHz)，2.54(lH，dd，J = 8.2，15.4Hz)，2.66(lH，dd，J = 4.4，15.4Hz)， 2.74(lH，dd，J = 6.3，12.6Hz)，2.91(3H，s)，2.93(lH，m)，2.99(lH， dd，J = 3.8，12.6Hz),3.30(lH，m)，3.83(1 H，d，J = 9.1Hz)，3.9-4.0 (3H，m)，4.12(lH，dt，J = 5.2,5.5Hz)，4.2(2H,m)，5.08(lH，m),5· 38(2H，m)，5.6 7(lH，d，J = 8.0Hz)，5.90(lH，t，J = 6.0Hz)，7.8 1(l H，d，J = 8.0Hz)，5.90(lH，t，J = 6.0Hz)，7.8 1(lH，d，J = 8.0)ppm 10) 13c-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞楓（39.5ppm )測 定，以下所示爲其13C -核磁共振光譜： 14.0(q)，19.4(q)，22.1(t)，24.6(t)，27.1(d)，28.7(t)，28.7(t)，28. 9(t)，29.0(t)，3 1.3(t)，3 3.2(t)，36.4(q)，37.8(q)，3 8.9(t)，39.8 (t)，3 9.9(t)，40.1(t)，40.4(t)，41.5(t)，56.6(t)，62.3(d)，66.6(d)， 69·1(d)，69.9(d)，70.7(d)，72.8(d)，77.6(d)，82.0(d)，83.9(d)，8 7.4(d)，101.3(d)，107.0(d)，140.5(d)，150.2(d)，163.3(s)，168· 5(s), 1 69.3(s)? 1 7 0.7 (8),1 7 1 .5 (8),1 7 3.8 (s)ppm 11 )高速液體色層分析法： 管柱：CAPCELLPAK C18UG12O,4.6 0 X 1 50mm (資生堂股 份有限公司製） 溶劑：含有ο.2%三乙基胺-磷酸緩衝液，調節ρΗ3·3255〇/〇 乙膪水溶液 流速：1 · 0 m 1 /分鐘 33- 200414902 檢出：紫外線吸收2 60nm 保持時間：4.0分鐘 (xi) 具有下列物理化學性狀之化合物或其鹽： 1)物質之性狀：無色粉末狀物質 2 )溶解性：可溶於甲醇、二甲亞珮，不溶於氯仿 3) 分子式：C54H85N5 023 4) 分子量：1171(以FAB質譜法測定） 5 )依高分解能F A B質譜法測定之精密質量，[μ + Η ] +如下列 表示ζ 實測値：1 1 7 2 · 5 7 3 1 計算値：1 1 7 2.5 7 1 3 6) 紫外線吸收光譜： 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表示： 263nm( £ 1 0400) 7) 旋光度： 於甲醇中測定旋光度，如下列所示値表示： [a ]D29 : + 1 0.6。（ c0.3 ) 8) 紅外線吸收光譜= 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下列 所示之極大吸收表示： 3403,2926,2855,1 739,1695,1628,1467,1 384,1273,1 1 62, 1 1 03,1 0 1 3,966cm·1 9) 1H-核磁共振光譜： •34- 200414902 重二甲亞碾中，內部標準使用重二甲亞楓（2.4 9ppm )測 定，以下所示爲其1H-核磁共振光譜：. 0.83(3H.t，J = 6.6Hz)，0.9 1(3H,d，J = 6.3Hz)，1.17(3H，d，J = 6.0 Hz)，l.2-1.3(18H，m),1.55(2H，m)，1.9-2.1(3H，m)，2.13(2H. m)，2.26(3H，s),2.3-2.4(3H，m)，2_4 1(lH，dd5J = 6.0,15.4Hz)，2. 47(2H，m)，2.6(4H，m)，2,80(lH，dd，J = 5.8，12.6Hz)，2.92(3H，s)， 2.9-3.0(2H，m)，3.20(lH，dd，J = 9.059.6Hz)，3.32(lH，m)，3.36 (3H5s)，3.37(lH，m)，3.3 8(3H，s)，3.4 1(lH，m)，3.52(lH，m)，3.5 9(lH，dq,J = 6.0,9.0Hz)，3.80(lH，d，J = 8.5Hz)53.9(2H，m)53.9 4(lH，d，J = 3.3Hz)，4.10(lH，m)，4.2 1(2H,m),4.94(lH，dd，J = 3. 0,9.6Hz)，5.11(lH，m)，5.37(2H，m)55.66(lH，d5J = 8.0Hz)，5.89 (lH，t，J = 5.5Hz)55.90(lH，d,J=1.4Hz)，7.8 1(lH，d，J = 8.0Hz)pp m 10) 13c-核磁共振光譜： 重二甲亞碾中，內部標準使用二甲亞碾（39.5ppm)測定， 以下所示爲其13C -核磁共振光譜： I4.0(q)，i7.7(q)，19.0(q)，22.1(t)，24.6(t)，27.1(d)，28.7(t)，28. 7(t)，28.9(t)，29.0(t)，2 9. l(t)，3 1 .3(t)，33.3(t)，3 6.3(q)，3 7.8 U)，3 8.8(t)，39.8(t).39.9(t)，40.0(t)，40.2(t)，4 1.4(t)，56.6(t)， 5 8.7 (q) ? 6 0.2 (q)? 6 2.4(d), 6 6.4(d) ,6 9.0(d), 6 9.6(d), 7 0.0(d) ,7 0.5(d),72.5(d),72.8(d),76.7(d),77.4(d),79.2(d),82.0(d),84. 〇(d)，87.2(d)，90.4(d)，101.2(d)，107.0(d)，140.4(d)，150.2(5)， 163·3(5)，169·0(5)，169·3(5)，170·2(5)·170·7(5)，171·2(5)，17 1.8(5),173.5(5)ppm -35- 200414902 1 l)高速液體色層分析法： 管柱：資生堂股份有限公司製 溶劑：含有0.2%三乙基胺-磷酸緩衝液，調節pH33255% 乙腈水溶液 流速：1 .〇ml/分鐘 檢出·紫外線吸收2 6 0 n m 保持時間：6.5分鐘 (χϋ ) 具有下列物理化學性狀之化合物或其鹽： 1 )物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞®，不溶於氯仿 3) 分子式：C54H85N5 02 3 4) 分子量：1171(以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[M + H] +如下列 表示： 實測値：1 1 72.5 73 1 計算値：1 1 7 2 · 5 7 1 3 6) 紫外線吸收光譜： 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表禾· 262nm( ε 1 1 000) 7) 旋光度： 於甲醇中測定旋光度，如下列所不値表不· ：+ 14.2° ( c0.2) 8 )紅外線吸收光譜： 200414902 以溴化鉀（KB r )錠劑法測定之紅外線吸收光譜以下列 所示之極大吸收表示： 3368,2927,2856,1735,1707,1674,1 651，161 5, 1466,1378， 1 2 7 6,1 1 6 1,1 1 04,95 1 cm-1 9) iH-核磁共振光譜： 重甲醇中，內部標準使用重甲醇（4.7 8ppm )測定，以下 所示爲其1H-核磁共振光譜：. 〇.76(3H，t，J = 7.0Hz),0.8 1(3H，d，J = 7.4Hz)，0.90(3H，d，J = 6.4 Hz)，1.2-1.3(18H，m)，1.37(lH5m)，1.51(2H，m)，1.68(lH，m)，2· l-2.2(4H，m)，2.2-2.4(5H，m)，2.42(3H,s)，2.5-2.6(6H，m)，2.8 5(lH，dd，J=8.3，13.4Hz)，3.0(2H，bi:，d)53.09(lH，dd，J = 4.0，13· 4Hz)，3.22(lH，dd，J = 9.0,9.0Hz)，3.32(3H，s)，3.34(3H，s)，3.3 7(lH，m)，3.49(lH，dd，J = 2.3,3.3Hz)，3.8(lH，bir，d)，4.0(2H，m)， 4.10(lH，dd5J = 6.0,6.4Hz)54.2(2H5m)54.26(lH，dd，J = 2.0,8.7 Hz)，4.96(1 H，dd，J = 3.3,9.0Hz)，5· 14(lH，m)，5.2-5.4(1 H，br m)，5.41(lH，t，J = 4.9Hz)，5.94(lH，t，J = 5.0Hz)，7.71(lH，d，J = 8· 〇Hz)ppm 1 0 ) 13 C -核磁共振光譜： 重二甲亞颯中，內部標準使用重甲醇（49. Oppm)測定， 以下所示爲其13C -核磁共振光譜： 1 0. 1 (q)，14.5(q)，20. l(q)，23.8(t)，25.6(t)，26.3(t)，28.9(d)，29. 8(t)，3 0.3(t)，30.4(t)，30.5(t)，30.6(t)，30.7(t)，30.8(t)533.9(t)， 35.3(t)，37.0(q)，40.7(t)，40.8(t),41.2(t)，41.5(t)，58.4(t)559· 7U),6 l.〇(q)，62.6(d)，66.3(d)，68.8(d)，69.4(d)，69.7(d)，72.0 -37- 200414902 (d)，72.9(d)，73 ·0(〇!)，74.8(d)，76.2(d)，78.6(d)，79.3(d)，84.2( d)，86.6(d)，87·1(d)，92.4(d)，103.3(d)，109.1(d)，144.3(d)，14 1.9(s)?164.4(s)5165.8(s)5l 70. l(s)?171.0(s)?172.2(s)5173.6 (s)，175.9(s)ppm 1 1)筒速液體色層分析法： 管柱：CAPCELLPAK C18UG120,4.6 0 χ 1 50mm (資生堂股 份有限公司製） 溶劑：含有〇 · 2 %三乙基胺-憐酸緩衝液，ρ Η 3 · 3之5 5 °/〇乙腈 水溶液調節 φ 流速：l.Onil /分鐘 檢出：紫外線吸收2 60nm 保持時間：7.0分鐘 本發明係關於一般式（I)乃至（IV)中任1項之一般式所表示 之構造所形成之化合物，或，具有⑴乃至（vii)及（x)乃至（xii) 中記載之物理化學性狀之化合物，稱爲「姆拉明黴素類抗 生素」之化合物。 本發明之姆拉明黴素類抗生素包含一般式（I)乃至（IV)中 鲁 任1項之一般式所表示之全部化合物，較佳者中R爲烴鏈之 化合物，前述烴鏈並未特別限定，可爲含有直鏈狀烴、分 枝狀烴、飽和烴、不飽和烴等，較佳爲直鏈狀烴鏈，更較 佳爲直鏈狀飽和烴鏈。烴鏈之長度未特別限定，但較佳爲 碳數7至17者，更佳者爲碳數9至15者。 本發明之姆拉明黴素類抗生素之具體例，可列舉下列％ 但未限定於此。 -38- 200414902 姆拉明黴素A(Muraminomicin A)爲上述一般式（I)中R爲― (CH2)3CH = CH(CH2)5CH3之化合物或有上述（i)中記載所示物 理化學性狀之化合物。同樣地，姆拉明黴素B(Miiramin〇micin B)係R爲-(CH2)9CH3之化合物或含有上述（ii)中記載所示物 理化學性狀之化合物，姆拉明黴素C(Muramin〇micin C)係R 爲- CH2CH = CH(CH2)7CH3之化合物或含有上述（iii)中記載之 物理化學性狀之化合物，姆拉明黴素D(Muraminomicin D) 係&爲-((^2)'11 = (：11(：112(^ = (：11((：112)，1之化合物或含有 上述（i v)中記載之所示物理化學性狀之化合物，姆拉明黴素 El(Muraminomicin E1)係 R爲 _ (CH2)8CH(CH3)2 之化合物或含 有上述（v)中記載之所示物理化學性狀之化合物，姆拉明黴 素 E2(Mui:aminomicin E2)係 R爲-(CH2)3CH = CH (CH2)6CH3 之 化合物或含有上述（vi)中記載之所示物理化學性狀之化合 物’姆拉明黴素F(Muraminomicin F)係R爲-(CH2)1QCH3之化 合物或含有上述（vii)中記載之所示物理化學性狀之化合 物。 又’姆拉明黴素類抗生素中，姆拉明黴素G(Muramin〇micin G)係上述一般式（II)中，r爲-(CH2)1()CH3之化合物或含有上 述（X)中記載之所示物理化學性狀之化合物，姆拉明黴素Η (Muraminomicin Η)係上述一般式（ΠΙ)中 R爲·（{：Η2)1()(：Η3 之化 合物或含有上述（xi)中記載之所示物理化學性狀之化合物、 姆拉明黴素I(Mui:aminomicin I)係上述一般式（IV)中R爲-(CH2) 10CH3之化合物或含有上述（xii)中記載之所述物理化 學性狀之化合物。 -39- 200414902 本發明中，式（v)乃至（VIII)中任1項中所表示之化合物稱 爲「姆拉明黴素母核物質」、姆拉明黴素母核物質中’姆 拉明黴素Zl(Muraminomicin Z1)爲上述式（V)所表不之化合 物或含有如上述（v i i i)中記載之物理化學性狀之化合物，姆 拉明黴素Z2(Muraminomicin Z2)係上述式（VI)所不之化合物 或含有如上述（ix)中記載之物理化學性狀之化合物，姆拉明 徵素23(]\411^111丨11〇111丨(：丨1123)係上述式（^11)所75化合物’姆 拉明黴素Z4(Muraminomicin Z4)爲上記式（VIII)所不化合 物。 鲁 本發明中，姆拉明黴素類抗生素及姆拉明黴素母核物質 統稱爲「姆拉明黴素物質」。 本發明化合物對於現在問題包含迫切對耐性菌提供細菌 感染症之預防及治療爲可能的。又，該化合物作爲具有較 優異抗菌活性之衍生物時之起始原料亦爲可能。 本發明之化合物含有至少一個不對稱碳原子，而存有各 種光學異構物，一般式⑴乃至（IV)及式（V)乃至（VIII)中， 係以此等異構物之單一式表示，但本發明爲含有外消旋化 鲁 合物之異構物、及其異構物之混合物方式。此等異構物依 立體特異的合成法，若光學活性化合物作爲原料化合物合 成時則能夠製造，或，以異構物之混合物製造後，使用色 層分析等習用方法分離爲可製造所冀望之異構物。 由於本發明化合物具有羧基、胺基等，使用此項業者中 習知方法能夠做成酸或鹼之鹽類，而本發明亦包含此等鹽。 本發明化合物之鹽作爲醫藥使用之場合，醫學上使用時， -40- 200414902 只要是藥理學上容許者則未特別限定。又’本發明之化合 物之鹽使用於醫藥以外用途之場合時’例如作爲中間體使 用之場合，只要能使用於該用途者，未特別限定。 此等鹽可列舉例如鈉鹽、鉀鹽、鋰鹽等之鹼金屬鹽；鈣 鹽、鎂鹽等之鹼土金屬鹽；鋁鹽、鐵鹽、鋅鹽、銅鹽、鎳 鹽、鈷鹽等之金屬鹽；銨鹽等之無機鹽；t-辛基胺鹽、二 苄胺鹽、嗎啉鹽、葡糖胺、苯基甘胺酸烷基酯鹽、乙二胺 鹽、N-甲基葡糖胺鹽、胍鹽、二乙基胺鹽、三乙基胺鹽、 二環己基胺鹽、N，N’-二苄基乙二胺鹽、氯普羅卡因鹽、普 鲁 羅卡因鹽、二乙醇胺鹽、N-苄基-苯乙基胺鹽、哌畊鹽、四 甲基氨鹽、參（羥基甲基）胺甲烷鹽等之有機胺鹽；甘胺酸 鹽、離胺酸鹽、精胺酸鹽、鳥胺酸鹽、天冬醯胺酸鹽等之 胺基酸鹽；乙酸鹽、溴化物鹽、氯化物鹽、鹽酸鹽、溴酸 鹽、碘化物鹽、硫酸鹽、磷酸鹽、二磷酸鹽等之無機鹽； 及檸檬酸鹽、順丁烯二酸鹽、雙羥萘酸鹽、酒石酸鹽等之 有機酸鹽等。較佳者爲藥理學上容許鹽，更佳者爲鈉鹽、 鉀鹽、鹽酸鹽、銨鹽、雙羥萘酸鹽。 籲 又，本發明之化合物及其鹽，於大氣中放置會與水或有 機溶劑混和而與水或溶劑結合，可形成水合物或溶劑化物 時，本發明亦包含此等水合物及溶劑化物之「藥理上容許 鹽」。 本發明之姆拉明黴素物質，較佳爲姆拉明黴素類抗生素， 係培養屬於鏈孢囊菌屬之菌株，可自此種培養液中得到。 又，姆拉明黴素母核物質可爲單獨姆拉明黴素類抗生素或 -41- 200414902 於混合物狀態經還原或水解而得到。 本發明之姆拉明黴素物質之製造法中使用屬於鏈孢囊菌 (Streptosporangium)屬之菌株’例如可列舉如鏈孢囊菌屬 (Streptosporangium sp.)SANK60501 株。SANK60501 株之囷 學特徵說明如下。 1 .形態學特徵 SANK60501株以ISP[國際鏈黴菌計畫，International streptomyces Project]規定之瓊脂培養基，於28°C培養Μ 日後之形態學特徵表示，以光學顯微鏡觀察，顯示 鲁 SANK6 0 5 0 1株之基礎菌絲有良好之伸長性，分枝，褐色、 淺褐色、淡紅褐色至褐紫色，但未觀察到奴卡氏菌 (Nocardia)屬菌株之菌絲斷裂或鋸齒形伸長樣，氣菌絲 之形成爲比較貧弱之單純分枝，顯示白色至粉白色，氣菌 絲之頂端或側生孢子之柄上著生球狀之孢子囊孢子，其大 小爲2至ll#m，孢子囊孢子呈橢圓形，爲0.9x 1.4//m， 不認爲孢子囊孢子有遊走性。 2 .各種培養基上之諸性質 ® 以各種培養基2 8 °C培養1 4日後之性狀示於表1， SANK6 0 5 0 1株菌於瓊脂培養基中多數產生紫色之針狀結 晶。依據曼賽努（Munsell)方式之日本色彩硏究所版「標準 色票」之色卡號碼表示其色調。 -42- 200414902 【表1】 培養基之種類 項目* 1 SANK60501株之性狀 蔗糖•硝酸鹽瓊脂 G 不怎麼良好，***狀，褐白色 (2.5Y 9/1)* 2 AM 不良，絲絨狀，粉白色（10YR9/2) R 淺粉紅色（10R8/3) SP 未產生 葡萄糖•天冬胺酸瓊脂 G 不良，無色 AM 未著生 R 無色 SP 未產生 甘油·天冬胺酸瓊脂（ISP G 不良，***狀，褐白色（2.5Y 9/1) 5) AM 不良，原痕跡的，白色 R 褐白色（2.5Y 9/1) SP 未產生 澱粉•無機鹽瓊脂（ISP G 不怎麼良好，***狀，褐色 4) (7.5YR4/4) AM 未著生 R 暗褐色（7.5YR3/3) SP 未產生 酪胺酸瓊脂（ISP 7) G 不良，***狀，淡紅褐色 (10R5/4) AM 不良，原痕跡著生，白色 R 灰紅褐色（10R4/4) SP 未產生 營養瓊脂（Difco) G 不怎麼良好，***狀，亮褐色 (5YR5/8) 200414902 AM 未著生 R 灰橄欖色（5Y4/4) SP 未產生 酵母菌提取物•麥芽提 G 良好，***狀，褐紫色（1()R3/3) 取物（ISP 2) AM 未著生 R 暗紅紫色（10R3/4) SP 未產生 燕麥片瓊脂（ISP 3) G 不怎麼良好，平坦，暗紅褐色 (2.5YR3/3) AM 未著生 R (5YR3/4) SP 未產生 水瓊脂 G 不良，褐白色（10YR 9/1) AM 不良’原痕跡的’粉白色（10R 9/2) R 黃灰色（10Y 9/1) SP 未產生 馬鈴薯提取物•人參提 G 不良好，淡黃橙色（10YR 8/3) 取物瓊脂 AM 未著生 R 淡黃褐色（l〇YR 7M) SP 未產生 * 1 「G」代表生長 、「AM」 代表氣菌絲、「R」代表裡 面、「SP」代表可溶性色素。 * 2 性狀欄內之（） 內爲曼賽努方式之色調表示。 3. 生理學性質 28°C培養後，於2至21日間觀察SANK6050 1株之生理 -44- 200414902 學性狀如表2所示。 表2_ 澱粉之水解 陽性 明膠之液化 陰性 硝酸鹽之還原 陰性 牛奶之腺化 陰性 牛奶之凝固 陰性 黑色素樣色素之生產性陰性 (培養基1 ) 1 (培養基2) *陰性 (培養基3 ) *陰性 基質分解性 酪蛋白 陽性 酪胺酸 陽性 黃嘌呤 陰性 生長溫度範圍 (培養基4 ) 1 1 2 - 3 8 °C 生長適合溫度 (培養基4 ) 1 3 0 - 3 6 °C 食鹽耐性 3% -45- 1 :培養基1 :胰蛋白•酵母菌提取物·肉汁培養基 (ISP 1 ) 培養基2 :腺·酵母菌提取物·鐵瓊脂（ISP 6 ) 培養基3 :酪胺酸瓊脂（IS P 7 ) 培養基4 :酵母菌提取物·麥芽提取物瓊脂（ISP 2 ) 200414902 又，使用 Pridham and Gottlieb 瓊脂培養基（ISP 9) ，28 °C培養1 4日後觀察本菌株碳源之消化性示於表3中。 表3 D-葡萄糖 + D-果糖 + L-阿戊糖 + L-鼠李糖 土 D-木醣 + 蔗糖 士 肌醇 — 棉實糖 — D -甘露糖醇 士 對照 — 表3中「+」表示利用，「土」表示較弱利用，「—」表示 不利用。 4 · 化學分類學性質 SANK6 05 0 1株之化學分類學性狀依據「放線菌之分類與 鑑定」（日本放線菌學會編，日本學會事務中心，200 1年， Ρ·49-82 )如下所示。全細胞中主要檢測出糖成分，細胞壁 肽聚糖中胞壁酸（muramicacid)之醯基型爲乙醯基型。又， 主要甲基萘醒類（維生素K3類，menaquinon)分子種爲檢 測出 MK-9 ( H。）、MK-9 ( H2 )及被 MK-9 ( H4 )，磷脂質 爲PIV型，未檢測出黴菌酸。 本菌株之分類係依據ISP [國際鏈黴菌計畫，lute national streptomycesProject]基準、渥克斯著，「放線菌」，第2 卷（S. A.Waksman，’’The Actinomycetes’’，2)，布奇納與奇柏 編，「伯格氏參考指南」，第8版，1 974年（R.E.Buchananand、 N.E. Gibbons, MBergey!s Manual of Determinative Bacteriology’’，8th edition，1974)， 「伯格氏參考指南」，第 -46- 200414902 4 卷，1989 年（Bergey’s Manual of System ati’c Bacte riol〇gy，4，1 9 8 9)，「放線菌之分類與鑑定」，日本放線菌學 會編，日本學會事務中心，2001年（Identification Manual of Actinomycetes)及鏈孢囊菌（Streptosporangium)屬放線菌相 關之最近文獻，放線菌中爲鏈孢囊菌（Streptosporangium) 屬。因此，鑑定本菌株鏈孢囊菌屬（Streptosporangium sp·) SANK60501 株（本說明書中稱爲「SANK60501 株」）。又，本 菌株於2002年3月27日國際寄託於日本茨城縣筑波市東1丁 目1番地1之獨立行政法人產業技術綜合硏究所專利生物寄 存中心，授與受託編號FERM BP-79 84號。 放線菌於自然界中或人工操作（例如紫外線照射、放射線 照射、化學藥品處理等）後，容易產生變異爲周知之事，本 發明之SANK60 5 0 1株亦同樣地，但本發明之SANK6050 1株， 包含此等變異株之全部。又，此等變異株亦包含以遺傳學 學之方法，例如重組、形質導入、形質轉等得到者。 因此’ SANK605 0 1株生產姆拉明黴素物質，較佳爲姆拉 明黴素類抗生素，其變異株及與其無法明確區別之菌株， 全部包含於SANK605 0 1株中。 又’本發明包含屬於鏈孢囊菌屬之生產姆拉明黴素物質， 較佳爲生產姆拉明黴素類抗生素之全部菌株。 培養本發明之姆拉明黴素物質之生產菌時使用之培養 基’可含有選擇自碳源、氮源、無機離子及有機營養源等 之適宜培養基，合成或天然培養基中任一種皆可使用。 該營養源爲先前公知之真菌類或放線菌類菌株之培養所 -47- 200414902 利用者，可使用微生物可代謝之碳源、氮源及無機鹽。 具體而言，作爲碳源者爲葡萄糖、果糖、麥芽糖、蔗糖、 甘露糖醇、甘油、糊精、燕麥、黑麥、玉米澱粉、馬鈴薯、 玉米粉、大豆粉、棉實油、水飴、糖蜜、大豆油、檸檬酸、 酒石酸等爲單一或合倂使用。一般性之上述碳源可使用培 養基之量之1至10重量％，但並未限定其範圍。 又，氮源可使用含有蛋白質或其水解物之物質，或含氮 無機鹽類，較佳之氮源，例如可使用大豆粉、_、落花生 粉、綿實粉、脫脂奶粉、酪蛋白水解物、法嗎明（pharmamin)、 φ 魚粉、玉米浸漬液、腺、肉提取物、生酵母菌、乾燥酵母 菌、酵母菌提取物、馬路托（m a r u t 〇 )提取物、馬鈴薯、 硫酸錢、硝酸銨、硝酸鈉等。該氮源於單一或合倂使用， 較佳使用培養基量之0.2乃至6重量％之範圍。 再者，營養無機鹽可使用包含鈉、銨、鈣、磷酸根、硫 酸根、氯化物、碳酸根等離子之習用鹽類。 又，爲液體培養基時，可使用作爲消泡劑之砂油、植物 油、界面活性劑等。 # 培養SANK6 050 1株生產姆拉明黴素物質之培養基pH値較 佳爲5.0至8.0。 SANK6 0501株之生長溫度爲12乃至38t，但爲了生產姆 拉明黴素物質，培養該菌株培養於18乃至36t爲較佳，更 佳爲培養於20乃至32°C。 姆拉明黴素物質係好氣性培養SANK6〇5〇l株所得者，而 此等培養法可以通常習用之好氣培養法，例如可使用固體 -48- 200414902 培養法、震盪培養法、通氣攪拌培養法等。 於小規模之培養，進行2 0至3 2 °C震盪培養數日爲較佳， 此培養隔以折流板（水流調節壁），或者不隔於三角燒瓶中， 以1或2個階段之種培養步驟開始。 種培養階段之培養基中可倂用碳源及氮源。種培養於20 乃至3 2 °C之恆溫培養箱中，8日間震盪，或震盪至充分成長 後進行。生長之種於第二種培養基或生產培養基中接種。 使用中間生長步驟時，可進行與種培養同樣之方法。中 間生長步驟所得之種，將其一部份接種於生產培養基中。 生產之培養可將此種接種於生產培養用燒瓶中於一定溫 度下數日震盪培養進行。 進行大量生產培養時，以攪絆機、通氣裝置附隨於發酵 器或槽中培養者爲較佳。其中，首先將營養培養基於121乃 至1 3 0 °C加熱滅菌，將其冷卻，之後，將以前述方法生長之 種接種於該滅菌培養基。之後培養於20乃至32°C通氣攪絆 下進行，以此方法可適當獲得多量化合物。 培養終了後，將燒瓶內之培養物離心分離或過濾，或提 取使用之培養物全體，經由純化可得到目的化合物。 伴隨培養經過所生產之姆拉明黴素物質之量，採取培養 液之一部份而提取該化合物群，測定轉位酵素I抑制活性而 確認該化合物之總活性量，又，進行高速液體色層分析， 可個別監測以測定該化合物群。姆拉明黴素物質之生產量 通常以3至15日達到最局値。 培養終了後，培養液中之液體部分及菌體內，或存在於 • 49- 200414902 雙方之姆拉明黴素物質，將培養終了液之全部，或菌株， 其他固形部分，分別以矽藻土之助過濾劑過濾或離心分離， 所彳守濾液或上淸液及囷體中’以轉位酵素I抑制活性或高速 液體色層分析爲指標，利用其物理化學性狀提取而純化。 濾、液或上淸液中存在之姆拉明黴素物質，於中性Ρ Η條件 下’以與水不能混和之有機溶劑，例如以乙酸乙酯、氯仿、 二氯乙烷、氯化苯乙烯、丁醇等之單獨或此等之組合提取 純化。又’作爲吸著劑者，例如可使用活性碳或吸著用樹 脂阿姆伯拉特又八0-2、父八0-4(登錄商標，&〇}1111&11(11^&5公 司製）等或 DiaionHP-10、HP-20、CHP-20P、ΗΡ-50、 SEPABEADS SP-207(登錄商標，三菱化學公司製）等提取純 化。使用吸著劑提取純化時，將含目的化合物之溶液通過 吸著劑之層，不純物會被吸著劑吸著而去除，又，吸著目 的化合物之不純物洗去流出後，使用甲醇水溶液、乙腈水 溶液、丁醇水溶液等將目的化合物洗析出，可提取純化目 的化合物。 可以50乃至90 %之含乙腈或含水甲醇中提取，去除濃縮操 作之有機溶劑後，進行上述同樣之提取純化操作而得到菌 體內存在之姆拉明黴素物質，例如，於培養終了後取適當 量（較佳爲終濃度5 0 %)，添加乙腈或甲醇可提取目的化合 物。提取終了後，不進行以矽藻土之助過濾劑之過濾操作， 得到之提取液與濾液相同的提取純化操作進行提取純化目 的化合物。 依上述方法提取純化之含姆拉明黴素物質之溶液使用矽 -50- 200414902 膠、交聯葡聚糖（Sephadex)LH-20(Amershambiosciences公 司製）、砂酸鎂固相萃取（Florisil)(NacalaiTesque公司製）等 載體分配管柱色層分析；使用Diaion CHP-20P(三菱化學公 司製）等之載體吸著管柱色層分析；使用交聯葡聚糖G-10(Amershambiosciences公司製）、TOYOPEARLHW40F(Toso 公司製）等之膠體過濾色層分析；使用DOWEX50(日產化學 公司製）DOWEX 1(日產化學公司製）、Diaion PK216(三菱化 學公司製）、Diaion ΡΑ316(三菱化學公司製）、CM交聯葡聚 糖 C -25(Amershambiosciences公司製）、DEAE交聯葡聚糖 A 一25(Amershambiosciences公司製）等之離子交換色層分 析，及使用順層、逆層管柱之局速液體色層分析等進一步 純化。 以上之分離、純化方式可單獨或適宜組合使用，依據場 合反覆使用可分離純化本發明之姆拉明黴素物質。 以業者周知之方法，將姆拉明黴素A、姆拉明黴素B、姆 拉明黴素C、姆拉明黴素D、姆拉明黴素E1、姆拉明黴素E2、 姆拉明黴素F、姆拉明黴素G或姆拉明黴素Η等，如一般式（I) 乃至（III)中任1項所示之姆拉明黴素類抗生素之單獨或混合 物狀態還原或水解而得到姆拉明黴素Ζ 1或姆拉明黴素Ζ2。 姆拉明黴素Ζ3或姆拉明黴素Ζ4，可以業者周知之方法， 將姆拉明黴素I等，如一般式（IV)所示姆拉明黴素類抗生素 之單獨或混合物狀態還原或水解而得到。 還原，例如可於溶劑中，將姆拉明黴素類抗生素以氫氧 化硼鋰或氫化硼鈉等作用而達成。 -51- 200414902 所使用之溶劑可列舉如甲醇、乙醇等之醇或四氫呋喃等， 較佳爲四氫呋喃。 水解係於例如有機溶劑之存在下或不存在下，將姆拉明 徵素A、姆拉明黴素B、姆拉明黴素姆拉明黴素〇、姆拉 明黴素E 1、姆拉明黴素E 2或姆拉明黴素F於鹼性或酸性條件 下而達成。 所使用之溶劑可列舉水；甲醇、乙醇、異丙醇之醇類； 四氫咲喃或此等溶劑之2種以上之混合物，較佳爲水。 驗性化合物可列舉如鈉、鉀、鋰等之鹼金屬氫氧化物或 其弱酸鹽；鈣鹽、鎂鹽等之鹼土金屬氫氧化物或其弱酸鹽； 氨等之無機鹼性化合物或所示鹼性鹽；t_辛基胺、二苄基 胺、嗎啉、葡糖胺、苯基甘胺酸烷基酯、乙二胺、N_甲基 葡糖胺、胍、二乙基胺、三乙基胺、二環己基胺、N，N，-二 ;基乙二胺、氯普羅卡因、普羅卡因、二乙醇胺鹽、N —苄 基-苯乙基胺鹽、哌畊鹽、四甲基氨鹽、參（羥基甲基）胺甲 院鹽等之有機胺；或所示鹼基之鹽。又此等鹼金屬離子； 含有驗土金屬離子、氨等之無機離子、有機胺離子等之鹼 性緩衝液可使用’較佳者爲鹼金屬氫氧化物，更佳者爲氫 氧化鈉或氫氧化鉀。 酸性化合物可列舉鹽酸、氫溴酸、硫酸、過氯酸、磷酸 等之無機酸或乙酸、甲酸、荏酸、甲烷磺酸、P-甲苯磺酸、 樟腦磺酸'三氟乙酸、三氟甲烷磺酸等之有機酸等布氏酸 (Bronsted acid);氯化鋅、四氯化錫、三氯化硼、三氟化硼、 三溴化硼等之路易士酸。 -52- 200414902 又，上述中，可將將姆拉明黴素A、姆拉明黴素B、姆拉 明黴素C、姆拉明黴素D、姆拉明黴素E1、姆拉明黴素E2、 姆拉明黴素F、姆拉明黴素G或姆拉明黴素Η中，如一般式（I) 乃至（ΠΙ)中任一者所示之姆拉明黴素類抗生素以金屬醇鹽 作用得到姆拉明黴素Ζ 1或姆拉明黴素Ζ 2。 又，姆拉明黴素Ζ3或姆拉明黴素Ζ4，如姆拉明黴素I之一 般式（IV)所示姆拉明黴素類抗生素以金屬醇鹽作用得可得 到。 所使用之溶劑可列舉如甲醇、乙醇、t- 丁醇等之醇類或 四氫呋喃。 醇金屬鹽可列舉如爲鈉甲醇鹽、鉀甲醇鹽、鈉乙醇鹽、 鉀乙醇鹽、鈉第三丁醇鹽、鉀第三丁醇鹽等，較佳爲鈉甲 醇鹽或鈉乙醇鹽。 所得到之姆拉明黴素Z1或姆拉明黴素Z2以 COSMOSIL(Nacalai Tesque公司製）等之載體之分配管柱色 層分析；使用Diai〇nCHP-20P(三菱化學公司製）等之載體之 吸者管柱色層分析；父聯葡聚糖G-10(Amershambiosciences 公司製）、TOYOPEARLHW40F(Toso公司製）等膠體5週色層 分析；DOWEX50(日產化學公司製）DOWEX 1(日產化學公 司製）、DiaionPK2 16(三菱化學公司製）、DiaionPA316(三 菱化學公司製）、CM交聯葡聚糖C-25(AmerShambi〇SCienCes 公司製）、DEAE父聯葡聚糖A-25(Amershambiosciences公司 製）等Diai on交換色層分析；或可使用順層、逆層管柱之高 速液體色層分析等純化。 -53- 200414902 以上之分離、純化手段單獨或適宜組合，依場合反覆使 用，可分離純化本發明之姆拉明黴素母核物質。 以上說明姆拉明黴素物質之製造法之代表性方法，但其 製造方法並未以此限定，亦可使用此等方法以外之業者已 知之其它製造方法。 本發明進一步係關於具有所冀望構造之姆拉明黴素類抗 生素之製造方法。 關於上述姆拉明黴素物質生產菌之培養，使用通常之培 養基中添加所望之脂肪酸，一般式（I)乃至（IV)，較佳爲一般 式（I)，其中R爲前述脂肪酸中對應烴鏈之姆拉明黴素類抗 生素之生產量增加而產出。所使用之脂肪酸爲主鏈之碳數 爲3以上者而未特別限定，可使用直鏈脂肪酸、分枝鏈脂肪 酸、飽和脂肪酸、不飽和脂肪酸等，較佳爲直鏈狀飽和脂 肪酸。直鏈狀飽和脂肪酸之鏈長爲碳數3以上而未特別限 定，但較佳爲碳數10至20，更佳爲碳數12至18。 例如，使用下述一般式（IX)所示脂肪酸時，生產量會增 加之姆拉明黴素類抗生素爲一般式（I)乃至（IV)中R = R1者，[a] D29: + 19.8 ° (c0.2) 8) Infrared absorption spectrum = The infrared absorption spectrum measured by the potassium bromide (KBr) tablet method is expressed by the maximum absorption shown below: 3394, 2926, 2855, 1737 , 1691, 1629, 1467, 1397, 1274, 1203, 1 131,1 094,1 0 1 3,962cm · 1 9) 1H-NMR spectrum: In heavy dimethylate, the internal standard uses heavy dimethyline ( 2.49ppm), 32-200414902, and the following is its 1 核 -NMR spectrum: 0.84 (3H, t, J = 7.1Hz), 0.88 (3H, d, J = 6.3Hz), 1.2-1.3 (18H , M), l. 57 (2H, m), 1.9-2.2 (8H, m), 2.24 (3H, s) 52.43 (lH, dd, J = 5.5-15. LHz), 2.54 (lH, dd, J = 8.2, 15.4 Hz), 2.66 (lH, dd, J = 4.4, 15.4 Hz), 2.74 (lH, dd, J = 6.3, 12.6 Hz), 2.91 (3H, s), 2.93 (lH, m), 2.99 (lH, dd, J = 3.8, 12.6 Hz), 3.30 (lH, m), 3.83 (1 H, d, J = 9.1 Hz), 3.9-4.0 (3H, m), 4.12 (lH, dt, J = 5.2, 5.5 Hz), 4.2 (2H, m), 5.08 (lH, m), 5.38 (2H, m), 5.67 (lH, d, J = 8.0Hz), 5.90 (lH, t, J = 6.0Hz), 7.8 1 (l H, d, J = 8.0 Hz), 5.90 (lH, t, J = 6.0 Hz), 7.8 1 (lH, d, J = 8.0) ppm 10) 13c-NMR spectrum: In heavy dimethanine, the internal standard is determined using heavy dimethanite (39.5ppm), and its 13C-NMR spectrum is shown below: 14.0 (q), 19.4 (q), 22.1 (t), 24.6 (t), 27.1 (d), 28.7 (t), 28.7 (t), 28.9 (t), 29.0 (t), 3 1.3 (t), 3 3.2 ( t), 36.4 (q), 37.8 (q), 3 8.9 (t), 39.8 (t), 3 9.9 (t), 40.1 (t), 40.4 (t), 41.5 (t), 56.6 (t), 62.3 (d), 66.6 (d), 69.1 (d), 69.9 (d), 70.7 (d), 72.8 (d), 77.6 (d), 82.0 (d), 83.9 (d), 8 7.4 ( d), 101.3 (d), 107.0 (d), 140.5 (d), 150.2 (d), 163.3 (s), 168.5 (s), 1 69.3 (s)? 1 7 0.7 (8), 1 7 1.5 (8), 1 7 3.8 (s) ppm 11) High-speed liquid chromatography analysis method: Column: CAPCELLPAK C18UG12O, 4.60 X 1 50mm (made by Shiseido Co., Ltd.) Solvent: Contains ο 2% triethyl Base amine-phosphate buffer solution, adjust the flow rate of ρΗ3.3255 / acetic acid aqueous solution: 1.0 m / min 33-200414902 Detection: UV absorption 2 60nm Hold time: 4.0 minutes (xi) It has the following physical and chemical properties Compound or its salt: 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethylarsine, insoluble in chloroform 3) Molecular formula: C54H85N5 023 4) Molecular weight: 1171 (determined by FAB mass spectrometry) 5) Precision mass determined by high decomposition energy FAB mass spectrometry, [μ + Η] + As shown below ζ Measured 値: 1 1 7 2 · 5 7 3 1 Calculate 値: 1 1 7 2.5 7 1 3 6) Ultraviolet absorption spectrum: Measure the ultraviolet absorption spectrum in methanol, and the maximum absorption expression is shown below : 263nm (£ 1 0400) 7) Optical rotation: The optical rotation was measured in methanol, as shown below: [a] D29: + 1 0.6. (C0.3) 8) Infrared absorption spectrum = The infrared absorption spectrum measured by the potassium bromide (KBr) tablet method is expressed by the maximum absorption shown below: 3403, 2926, 2855, 1 739, 1695, 1628, 1467, 1 384,1273,1 1 62, 1 1 03,1 0 1 3,966cm · 1 9) 1H-NMR spectrum: • 34- 200414902 In heavy dimethanine, the internal standard uses heavy dimethanine (2.4 9ppm) ), And its 1H-NMR spectrum is shown below: 0.83 (3H.t, J = 6.6Hz), 0.9 1 (3H, d, J = 6.3Hz), 1.17 (3H, d, J = 6.0 Hz ), 1.2-1.3 (18H, m), 1.55 (2H, m), 1.9-2.1 (3H, m), 2.13 (2H. M), 2.26 (3H, s), 2.3-2.4 (3H, m ), 2_4 1 (lH, dd5J = 6.0, 15.4 Hz), 2. 47 (2H, m), 2.6 (4H, m), 2,80 (lH, dd, J = 5.8, 12.6 Hz), 2.92 (3H , S), 2.9-3.0 (2H, m), 3.20 (lH, dd, J = 9.059.6Hz), 3.32 (lH, m), 3.36 (3H5s), 3.37 (lH, m), 3.3 8 (3H, s), 3.4 1 (lH, m), 3.52 (lH, m), 3.5 9 (lH, dq, J = 6.0, 9.0 Hz), 3.80 (lH, d, J = 8.5 Hz) 53.9 (2H, m) 53.9 4 (lH, d, J = 3.3Hz), 4.10 (lH, m), 4.2 1 (2H, m), 4.94 (lH, dd, J = 3. 0, 9.6Hz), 5.11 (lH, m) , 5.37 (2H, m) 55.66 (l H, d5J = 8.0Hz), 5.89 (lH, t, J = 5.5Hz) 55.90 (lH, d, J = 1.4Hz), 7.8 1 (lH, d, J = 8.0Hz) pp m 10) 13c-NMR Resonance spectroscopy: In heavy dimethanine, the internal standard was measured using dimethanine (39.5ppm), and its 13C-NMR spectrum is shown below: I4.0 (q), i7.7 (q), 19.0 ( q), 22.1 (t), 24.6 (t), 27.1 (d), 28.7 (t), 28.7 (t), 28.9 (t), 29.0 (t), 2 9. l (t), 3 1 .3 (t), 33.3 (t), 3 6.3 (q), 3 7.8 U), 3 8.8 (t), 39.8 (t). 39.9 (t), 40.0 (t), 40.2 (t), 4 1.4 (t), 56.6 (t), 5 8.7 (q)? 6 0.2 (q)? 6 2.4 (d), 6 6.4 (d), 6 9.0 (d), 6 9.6 (d), 7 0.0 (d) , 7 0.5 (d), 72.5 (d), 72.8 (d), 76.7 (d), 77.4 (d), 79.2 (d), 82.0 (d), 84.0 (d), 87.2 (d), 90.4 (d), 101.2 (d), 107.0 (d), 140.4 (d), 150.2 (5), 163.3 (5), 169.0 (5), 169.3 (5), 170 · 2 (5 ) · 170 · 7 (5), 171.2 (5), 17 1.8 (5), 173.5 (5) ppm -35- 200414902 1 l) High-speed liquid chromatography analysis method: Column: solvent made by Shiseido Co., Ltd. : Contains 0.2% triethylamine-phosphate buffer solution, adjusts pH to 33255% acetonitrile aqueous solution. Flow rate: 1.0 ml / min detection, UV absorption 2 6 0 n m Retention time: 6.5 minutes (χϋ) A compound or a salt thereof having the following physical and chemical properties: 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethylarene®, insoluble in chloroform 3) Molecular formula: C54H85N5 02 3 4) Molecular weight: 1171 (determined by FAB mass spectrometry) 5) Precise mass determined by high decomposition energy FAB mass spectrometry, [M + H] + as shown below: Measured 値: 1 1 72.5 73 1 Calculated 値： 1 1 7 2 · 5 7 1 3 6) Ultraviolet absorption spectrum: The ultraviolet absorption spectrum is measured in methanol, and the maximum absorption is shown below. 262nm (ε 1 1 000) 7) Optical rotation: The optical rotation is measured in methanol Degrees, as shown below: + 14.2 ° (c0.2) 8) Infrared absorption spectrum: 200414902 The infrared absorption spectrum measured by the potassium bromide (KB r) tablet method is expressed by the maximum absorption shown below : 3368,2927,2856,1735,1707,1674,1 651,161 5, 1466,1378, 1 2 7 6,1 1 6 1,1 1 04,95 1 cm-1 9) iH-NMR spectrum: In heavy methanol, the internal standard was determined using heavy methanol (4.7 8 ppm), and its 1H-NMR spectrum is shown below: 〇.76 ( 3H, t, J = 7.0 Hz), 0.8 1 (3H, d, J = 7.4 Hz), 0.90 (3H, d, J = 6.4 Hz), 1.2-1.3 (18H, m), 1.37 (lH5m), 1.51 (2H, m), 1.68 (lH, m), 2.1-2.2 (4H, m), 2.2-2.4 (5H, m), 2.42 (3H, s), 2.5-2.6 (6H, m), 2.8 5 (lH, dd, J = 8.3, 13.4 Hz), 3.0 (2H, bi :, d) 53.09 (lH, dd, J = 4.0, 13.4 Hz), 3.22 (lH, dd, J = 9.0, 9.0 Hz ), 3.32 (3H, s), 3.34 (3H, s), 3.3 7 (lH, m), 3.49 (lH, dd, J = 2.3, 3.3Hz), 3.8 (lH, bir, d), 4.0 (2H , M), 4.10 (lH, dd5J = 6.0, 6.4Hz) 54.2 (2H5m) 54.26 (lH, dd, J = 2.0, 8.7 Hz), 4.96 (1 H, dd, J = 3.3, 9.0Hz), 5. · 14 (lH, m), 5.2-5.4 (1 H, br m), 5.41 (lH, t, J = 4.9Hz), 5.94 (lH, t, J = 5.0Hz), 7.71 (lH, d, J = 8 · 〇Hz) ppm 1 0) 13 C-NMR spectrum: In heavy dimethylformene, the internal standard is determined using heavy methanol (49.0 ppm), and its 13C-NMR spectrum is shown below: 1 0.1 (q), 14.5 (q), 20.l (q), 23.8 (t), 25.6 (t), 26.3 (t), 28.9 (d), 29.8 (t), 3 0.3 (t), 30.4 (t), 30.5 (t), 30.6 (t), 30.7 (t), 30.8 (t), 533.9 (t), 35.3 (t), 37.0 (q), 40.7 (t ), 40.8 (t), 41.2 (t), 41.5 (t), 58.4 (t) 559 · 7U), 6 l.〇 (q), 62.6 (d), 66.3 (d), 68.8 (d), 69.4 (d), 69.7 (d), 72.0 -37- 200414902 (d), 72.9 (d), 73.0 (〇!), 74.8 (d), 76.2 (d), 78.6 (d), 79.3 (d) , 84.2 (d), 86.6 (d), 87.1 (d), 92.4 (d), 103.3 (d), 109.1 (d), 144.3 (d), 14 1.9 (s) to 164.4 (s) 5165.8 ( s) 5l 70. l (s)? 171.0 (s)? 172.2 (s) 5173.6 (s), 175.9 (s) ppm 1 1) Cylinder speed liquid chromatography analysis method: Tube column: CAPCELLPAK C18UG120,4.6 0 χ 1 50mm (manufactured by Shiseido Co., Ltd.) Solvent: 0.2% triethylamine-phosphoric acid buffer solution, ρ Η 3 · 3 of 5 5 ° / 〇 Acetonitrile aqueous solution to adjust φ flow rate: l. Onil / min detection: Ultraviolet absorption 2 60nm Holding time: 7.0 minutes The present invention is a compound formed by a structure represented by the general formula of any one of general formulae (I) to (IV), or having ⑴ or (vii) and (x) Even the compounds with physical and chemical properties described in (xii) are called "mramycin antibiotics". The mlamycin antibiotics of the present invention include all the compounds represented by the general formula of any one of the general formulae (I) to (IV). Preferably, R is a compound of a hydrocarbon chain, and the aforementioned hydrocarbon chain is not It is particularly limited, and may include a linear hydrocarbon, a branched hydrocarbon, a saturated hydrocarbon, an unsaturated hydrocarbon, and the like, preferably a linear hydrocarbon chain, and more preferably a linear saturated hydrocarbon chain. The length of the hydrocarbon chain is not particularly limited, but it is preferably one having 7 to 17 carbon atoms, and more preferably 9 to 15 carbon atoms. Specific examples of the mlamycin antibiotics of the present invention include the following%, but are not limited thereto. -38- 200414902 Muraminomicin A is a compound where R in the general formula (I) is-(CH2) 3CH = CH (CH2) 5CH3 or has the physicochemical properties shown in (i) above Of compounds. Similarly, miramycin B (Miramin omicin B) is a compound whose R is-(CH2) 9CH3 or a compound containing the physicochemical properties shown in (ii) above, and miramycin C (Muramin). micin C) is a compound in which R is-CH2CH = CH (CH2) 7CH3 or a compound containing the physicochemical properties described in (iii) above, and Muraminomicin D is-((^ 2 ) '11 = (: 11 (: 112 (^ = (: 11 ((: 112), 1 or a compound containing the physicochemical properties shown in (iv) above, musminicin El (Muraminomicin E1) is a compound in which R is _ (CH2) 8CH (CH3) 2 or a compound containing the physicochemical properties shown in (v) above, and Mram: mycin A2 (Mui: aminomicin E2) is in which R is-( CH2) 3CH = CH (CH2) 6CH3 or a compound containing the physicochemical properties shown in (vi) above, 'Muraminomicin F' is a compound whose R is-(CH2) 1QCH3 or contains The compound of the physicochemical properties shown in the above (vii). Among the mrammycin antibiotics, muraminomycin G is one of the above In the formula (II), a compound in which r is-(CH2) 1 () CH3 or a compound containing the physicochemical properties shown in (X) above, and Muraminomicin 系 is the general formula ( In ΠΙ), R is · ({:) 2) 1 () (: Η3 or a compound containing the physicochemical properties shown in (xi) above, and musmin A (Mui: aminomicin I) is the above A compound wherein R in the general formula (IV) is-(CH2) 10CH3 or a compound containing the physicochemical properties described in the above (xii). -39- 200414902 In the present invention, any of the formula (v) to (VIII) The compound represented by item 1 is called "mrammycin mother nucleus substance", and 'muraminomycin Zl (Muraminomicin Z1) in the mother laminamycin mother nucleus substance is not expressed by the above formula (V) Compounds or compounds containing physicochemical properties as described in (viii) above, Muramicin Z2 (Muraminomicin Z2) is a compound not included in formula (VI) or contains physicochemical properties as described in (ix) above The compound, Mlaminin 23 () \ 411 ^ 111 丨 11〇111 丨 (: 丨 1123) is the compound of 75 in the above formula (^ 11) 'Lamin Farm neomycin Z4 (Muraminomicin Z4) referred to the formula (VIII) are not compound. In the present invention, the mlaminomycin antibiotics and the mother nuclear substance of mlaminomycin are collectively referred to as "mramingin substance". The compounds of the present invention are possible for current problems including the urgent need to provide prevention and treatment of bacterial infections to resistant bacteria. It is also possible to use this compound as a starting material when it is a derivative having relatively excellent antibacterial activity. The compound of the present invention contains at least one asymmetric carbon atom, and various optical isomers exist. The general formulae ⑴ to (IV) and (V) to (VIII) are represented by a single formula of these isomers. However, the present invention is a method containing racemic isomers and mixtures of isomers thereof. These isomers can be produced according to stereospecific synthesis methods if the optically active compound is synthesized as a raw material compound, or after being produced from a mixture of isomers, they are separated into conventionally desired ones using conventional methods such as chromatographic analysis. Isomers. Since the compound of the present invention has a carboxyl group, an amine group, and the like, it is possible to form salts of acids or bases using a method known in the art, and the present invention also includes these salts. When the salt of the compound of the present invention is used for medicine, when used medically, it is not particularly limited as long as it is pharmacologically acceptable. In addition, when "the salt of the compound of the present invention is used for a purpose other than medicine", for example, when it is used as an intermediate, it is not particularly limited as long as it can be used for that purpose. Examples of such salts include alkali metal salts such as sodium, potassium, and lithium salts; alkaline earth metal salts such as calcium and magnesium salts; aluminum, iron, zinc, copper, nickel, and cobalt salts. Metal salts; inorganic salts such as ammonium salts; t-octylamine salt, dibenzylamine salt, morpholine salt, glucosamine, phenylglycine alkyl ester salt, ethylenediamine salt, N-methylglucose Sugar amine salt, guanidinium salt, diethylamine salt, triethylamine salt, dicyclohexylamine salt, N, N'-dibenzylethylenediamine salt, chloroprocaine salt, prolucaine salt Organic amine salts, such as diethanolamine salt, N-benzyl-phenethylamine salt, piperine salt, tetramethylammonium salt, ginsyl (hydroxymethyl) amine methane salt, etc .; glycine salt, lysine salt , Amine salts, spermine, ornithine, aspartate, etc .; acetate, bromide, chloride, hydrochloride, bromate, iodide, sulfate, Inorganic salts such as phosphates and diphosphates; and organic acid salts such as citrate, maleate, pamoate, tartrate, etc. Preferred are pharmacologically acceptable salts, and more preferred are sodium, potassium, hydrochloride, ammonium, and parabens. In addition, when the compounds of the present invention and their salts are placed in the air, they will mix with water or organic solvents and combine with water or solvents to form hydrates or solvates. The present invention also includes these hydrates and solvates. "Pharmacologically acceptable salt." The mlaminomycin substance of the present invention, preferably an antibiotic of the mrammycin class, is a strain belonging to the genus Streptococcus, which can be obtained from such a culture solution. In addition, the muraminycin mother nucleus substance can be obtained by reducing or hydrolyzing the mlamycin antibiotic alone or -41-200414902 in a mixture state. A strain belonging to the genus Streptosporangium 'is used in the production method of the mlaminomycin substance of the present invention, and examples thereof include a strain STeptosporangium sp. SANK60501. The characteristics of the SANK60501 strain are described below. 1. Morphological characteristics SANK60501 strain is expressed in ISP [International Streptomyces Project, International streptomyces Project] agar medium, cultured at 28 ° C, and the morphological characteristics of the day after being cultured. Observed with an optical microscope, it shows that SANK6 0 5 0 1 The basal mycelium of the strain has good elongation, branching, brown, light brown, light reddish brown to brown purple, but no mycelial break or jagged elongation of Nocardia strain was observed. The formation of silk is a relatively weak simple branch, showing white to pinkish white. The top of the aerial hyphae or the lateral spore handle is covered with spherical spore spores, the size of which is 2 to ll # m. It is oval, 0.9x 1.4 // m, and sporangiospores are not considered to be migratory. 2. Properties on various media ® The properties after 14 days of culture at 28 ° C in various media are shown in Table 1. Most of the SANK6 0 50 strains produced purple needle-like crystals on the agar medium. The color card number of the "Standard Swatch" version of the Japanese Color Research Institute based on the Munsell method indicates its hue. -42- 200414902 [Table 1] Types of culture medium * 1 Properties of SANK60501 strain Sucrose • Nitrate Agar G Not very good, bulging, brownish white (2.5Y 9/1) * 2 AM Poor, velvety, powdery white (10YR9 / 2) R light pink (10R8 / 3) SP does not produce glucose • Aspartic acid agar G is bad, colorless AM is not born R Colorless SP does not produce glycerol • aspartic acid agar (ISP G is bad, bulge Shape, brownish white (2.5Y 9/1) 5) AM bad, original trace, white R brownish white (2.5Y 9/1) SP does not produce starch • inorganic salt agar (ISP G is not very good, bulging, brown 4) (7.5YR4 / 4) AM is not born R dark brown (7.5YR3 / 3) SP does not produce tyrosine agar (ISP 7) G Poor, bulging, light reddish brown (10R5 / 4) AM Poor, original trace Implanted, white R gray reddish brown (10R4 / 4) SP does not produce nutritional agar (Difco) G is not very good, bulging, bright brown (5YR5 / 8) 200414902 AM Unimplanted R gray olive (5Y4 / 4) SP does not produce yeast extract • Malt extract G is good, bulging, brownish purple (1 () R3 / 3) Extraction (ISP 2) AM Not grown R Dark reddish purple (10R3 / 4) SP Not produced oatmeal agar (ISP 3) G Not very good, flat, dark reddish brown (2.5YR3 / 3) AM Unborn R (5YR3 / 4) SP No water agar G Defective, brownish white (10YR 9/1) AM bad 'Original trace' pinkish white (10R 9/2) R yellowish gray (10Y 9/1) SP No potato extract • Ginseng extract G is not good, light yellow orange (10YR 8/3) Extract agar AM is not grown R light yellow brown (lOYR 7M) SP is not produced * 1 "G" stands for growth, " "AM" stands for Aeromycelium, "R" stands for Inside, and "SP" stands for Soluble Pigment. * 2 The () in the character column is the hue expression of Mansenu method. 3. Physiological properties After 28 ° C cultivation, observe the physiological -44- 200414902 physiological characteristics of 1 SANK6050 strain from 2 to 21 days, as shown in Table 2. Table 2_ Starch hydrolysis-positive gelatin, liquefaction-negative nitrate, reduction-negative milk, adenitis-negative milk, coagulation-negative melanin-like pigment, production negative (medium 1) 1 (medium 2) * negative (medium 3) * negative matrix breakdown Casein positive tyrosine positive xanthine negative growth temperature range (medium 4) 1 1 2-3 8 ° C suitable growth temperature (medium 4) 1 3 0-3 6 ° C salt tolerance 3% -45- 1: Medium 1: Trypsin, yeast extract, gravy medium (ISP 1) Medium 2: Gland, yeast extract, iron agar (ISP 6) Medium 3: Tyrosine agar (IS P 7) Medium 4: yeast Extract · Malt extract agar (ISP 2) 200414902 Table 3 shows the digestibility of the carbon source of this strain after the culture at 28 ° C for 14 days using Pridham and Gottlieb agar medium (ISP 9). Table 3 D-glucose + D-fructose + L-pentose + L-rhamnose soil D-xylose + sucrose inositol-raffinose-D-mannitol control-"+" in Table 3 Indicates use, "soil" indicates weak use, and "-" indicates no use. 4 · Chemical taxonomic properties SANK6 05 0 The chemical taxonomic properties of 1 strain are based on "Classification and Identification of Actinomycetes" (edited by the Actinomycete Society, Japan Society Affairs Center, 2001, ρ 49-82) as shown below . The sugar component is mainly detected in the whole cell, and the amyl type of muramicacid in the cell wall peptidoglycan is the acetamyl type. In addition, the main methylnaphthalenes (vitamin K3, menaquinon) molecular species are MK-9 (H.), MK-9 (H2), and MK-9 (H4), and the phospholipids are of the PIV type. Mycotic acid was detected. The classification of this strain is based on the ISP [International Streptomyces Project, lute national streptomyces Project] benchmark, Wrox, "Actinomycetes", Volume 2 (SAWaksman, "The Actinomycetes", 2), Butchner With Chipper, "Burger's Reference Guide", 8th edition, 1 974 (REBuchananand, NE Gibbons, MBergey! S Manual of Determinative Bacteriology, 8th edition, 1974), "Burger Reference Guide" -46- 200414902 Volume 4, 1989 (Bergey's Manual of System ati'c Bacte riology, 4, 189 8 9), "Classification and Identification of Actinomycetes", edited by the Actinomycete Society of Japan, Japan Society Affairs Center, 2001 (Identification Manual of Actinomycetes) and recent literature related to Streptosporangium, which belongs to Streptosporangium. Therefore, this strain was identified as a strain Streptosporangium sp. SANK60501 (referred to as "SANK60501 strain" in this specification). In addition, this strain was deposited internationally on March 27, 2002 at the Patent Biostorage Center of the Institute of Industrial Technology Comprehensive Research, Independent Administrative Corporation, East 1-Chome, 1-Chome 1, Tsukuba City, Ibaraki Prefecture, Japan, and was awarded the trust number FERM BP-79 84. Actinomycetes in nature or after manual operation (such as ultraviolet irradiation, radiation irradiation, chemical treatment, etc.) are susceptible to mutation. It is a well-known thing. The same applies to SANK60 501 of the present invention, but to SANK6050 of the present invention. , Including all these variants. In addition, these mutants also include those obtained by genetic methods such as recombination, introduction of form, and transformation of form. Therefore, the ‘SANK605 01’ strain produces laminmycin material, preferably the miramycin antibiotics, and its variants and strains which cannot be clearly distinguished from it are all included in the SANK605 01 strain. Furthermore, the present invention includes all the strains producing mrammycin, belonging to the genus Streptococcus, and preferably all strains producing mrammycin antibiotics. The culture medium used when cultivating the bacterium for producing mramycin in the present invention may contain a suitable medium selected from a carbon source, a nitrogen source, an inorganic ion, an organic nutrient source, and the like, and any of synthetic or natural media may be used. This nutrient source is a previously known culture place for fungal or actinomycete strains. Users can use carbon sources, nitrogen sources, and inorganic salts that can be metabolized by microorganisms. Specifically, the carbon source is glucose, fructose, maltose, sucrose, mannitol, glycerol, dextrin, oats, rye, corn starch, potato, corn meal, soybean meal, cotton oil, wild rice, molasses, Soy oil, citric acid, tartaric acid, etc. are used singly or in combination. Generally, the carbon source can be used in an amount of 1 to 10% by weight based on the amount of the culture medium, but the range is not limited. In addition, as the nitrogen source, a substance containing protein or a hydrolyzate thereof, or a nitrogen-containing inorganic salt can be used. Preferred nitrogen sources include, for example, soybean powder, peanut powder, cotton powder, skimmed milk powder, casein hydrolysate, Pharmamin, φ fish meal, corn steep solution, gland, meat extract, raw yeast, dried yeast, yeast extract, marut 〇 extract, potato, sulphate, ammonium nitrate, Sodium nitrate and so on. The nitrogen source is used singly or in combination, and a range of 0.2 to 6% by weight of the medium is preferably used. Moreover, conventional salts containing sodium, ammonium, calcium, phosphate, sulfate, chloride, carbonate and the like can be used as the nutritional inorganic salt. In the case of a liquid culture medium, sand oil, vegetable oil, surfactant, etc. can be used as a defoaming agent. # Cultivate SANK6 050 The pH 値 of a culture medium for producing mlamycin is preferably 5.0 to 8.0. The growth temperature of SANK6 0501 strain is 12 to 38t. However, in order to produce laminmycin material, it is better to culture the strain at 18 to 36t, and more preferably at 20 to 32 ° C. Mlaminomycin material is obtained by aerobic culture of SANK 6050 strain, and these culture methods can be generally used in aerobic culture methods, such as solid-48-200414902 culture method, shaking culture method, aeration and agitation culture Law, etc. For small-scale cultivation, it is better to perform shaking culture at 20 to 3 2 ° C for several days. This culture is separated by baffles (water flow regulating walls) or not in an Erlenmeyer flask in 1 or 2 stages. This cultivation step begins. A carbon source and a nitrogen source can be used in the medium in the cultivation stage. The seeds are cultured in a constant temperature incubator at 20 to 32 ° C, and shaken for 8 days, or after shaking to full growth. Growing seeds are inoculated in a second or production medium. When an intermediate growth step is used, the same method as seed culture can be performed. The seeds obtained in the intermediate growth step are inoculated into a part of the production medium. Production culture can be carried out by inoculating the production culture flask with shaking culture at a certain temperature for several days. When mass production culture is carried out, it is preferable to use a stirrer or aeration device to accompany the culture in a fermenter or tank. Among them, the nutrient medium is first sterilized by heating at 121 or 130 ° C, and then cooled, and then the seeds grown in the aforementioned method are inoculated into the sterilization medium. After that, the culture is carried out at 20 to 32 ° C, and a large amount of compounds can be appropriately obtained by this method. After the culture is completed, the culture in the flask is centrifuged or filtered, or the entire culture used is extracted and purified to obtain the target compound. Along with the amount of mramycin produced by the culture, the compound group was extracted by taking a part of the culture solution, and the inhibitory activity of the translocation enzyme I was measured to confirm the total activity amount of the compound. Layer analysis can be monitored individually to determine the compound population. The production of lamminycin material usually reaches its peak within 3 to 15 days. After the end of the culture, the liquid part of the culture solution and the bacterial cells, or the laminmycin substance that exists in both sides of 49-200414902, will be the entire culture solution, or the strains, and other solid parts, respectively. Filtration or centrifugal separation of the filter aids, the filtrate or supernatant and the carcass are 'purified by the physical and chemical properties of the extract with the inhibitory activity of translocation enzyme I or high-speed liquid chromatography. Mlaminin substances present in filters, liquids or supernatants, under neutral pH conditions, in organic solvents that are immiscible with water, such as ethyl acetate, chloroform, dichloroethane, benzene chloride Extraction and purification of ethylene, butanol alone or a combination of these. As the sorbent, for example, activated carbon or absorbing resin Amberat 80-2, father 80-4 (registered trademark, & 〇) 1111 & 11 (11 ^ & 5 company), or DiaionHP-10, HP-20, CHP-20P, HP-50, SEPABEADS SP-207 (registered trademark, manufactured by Mitsubishi Chemical Corporation), etc. Extraction and purification using sorbent will include the purpose The solution of the compound passes through the layer of the sorbent. Impurities will be absorbed by the sorbent and removed. After the impurities of the target compound are washed away, the target compound will be washed out using methanol aqueous solution, acetonitrile aqueous solution, butanol aqueous solution, etc. The target compound can be extracted and purified. It can be extracted from 50 to 90% of acetonitrile or water-containing methanol. After removing the organic solvent of the concentration operation, the same extraction and purification operation as described above is performed to obtain the mrammycin substance existing in the bacteria, such as After the end of the culture, take an appropriate amount (preferably a final concentration of 50%) and add acetonitrile or methanol to extract the target compound. After the end of the extraction, the filtering operation with the diatomite-assisted filtering agent is not performed to obtain the extraction Extract and purify the target compound by the same extraction and purification operation as the filtrate. Use the silica-50-200414902 gel, Sephadex LH-20 (Amershambiosciences) Chromatography analysis of carrier distribution column such as Florisil (manufactured by Nacalai Tesque), Magnesium oxalate; Carrier column chromatogram analysis using carrier such as Diaion CHP-20P (Mitsubishi Chemical Corporation); Analysis of colloidal filtration chromatographic layers of bi-dextran G-10 (manufactured by Amershambiosciences), TOYOPEARLHW40F (manufactured by Toso); use of DOWEX50 (manufactured by Nissan Chemical Co.), DOWEX 1 (manufactured by Nissan Chemical Co., Ltd.), and Diaion PK216 (Mitsubishi Chemical Corporation) Manufactured), ion ion chromatography analysis of Diaion PA316 (made by Mitsubishi Chemical Corporation), CM crosslinked dextran C-25 (made by Amershambiosciences), DEAE crosslinked dextran A-25 (made by Amershambiosciences), and Further purification is performed by using local-layer, reverse-layer, column-level liquid chromatographic analysis, etc. The above separation and purification methods can be used alone or in combination as appropriate. It can be used repeatedly in occasions to isolate and purify the mrammycin substance of the present invention. According to a method known to the practitioner, the mrammycin A, mrammycin B, mrammycin C, and mrammycin D can be separated and purified. , Mrammycin E1, mrammycin E2, mrammycin F, mrammycin G, or mrammycin Η, etc., such as any one of general formula (I) and (III) The reduction or hydrolysis of the mlamycin antibiotics shown in item singly or as a mixture yields mlamycin Z1 or mlamycin Z2. Mlaminomycin Z3 or Mlaminomycin Z4 can be reduced by a method known to the practitioner, such as mlaminomycin I or the like, as shown in general formula (IV), alone or in a mixture. Or obtained by hydrolysis. The reduction can be achieved, for example, by using a liminomycin antibiotic in a solvent with lithium boron hydroxide or sodium borohydride. -51- 200414902 Examples of the solvent to be used include alcohols such as methanol and ethanol, and tetrahydrofuran. Tetrahydrofuran is preferred. The hydrolysis is performed, for example, in the presence or absence of an organic solvent, by combining mlaminin A, mlaminomycin B, mlamin Raminemycin E 2 or Mraminemycin F is achieved under alkaline or acidic conditions. Examples of the solvent to be used include water; alcohols of methanol, ethanol, and isopropanol; tetrahydrofuran or a mixture of two or more of these solvents, preferably water. Examples of the test compounds include alkali metal hydroxides or weak acid salts thereof such as sodium, potassium, lithium, etc .; alkaline earth metal hydroxides or weak acid salts thereof such as calcium salt, magnesium salt, etc .; inorganic basic compounds such as ammonia, or Basic salts shown; t-octylamine, dibenzylamine, morpholine, glucosamine, alkyl phenylglycinate, ethylenediamine, N-methylglucamine, guanidine, diethyl Amine, triethylamine, dicyclohexylamine, N, N, -di; ethyleneethylenediamine, chloroprocaine, procaine, diethanolamine salt, N-benzyl-phenethylamine salt, piperine Organic amines such as salts, tetramethylammonium salts, ginseng (hydroxymethyl) amine methylamine salts, etc .; or salts of the bases shown. These alkali metal ions; alkaline buffers containing inorganic metal ions, inorganic ions such as ammonia, organic amine ions, etc. can be used. 'The preferred is an alkali metal hydroxide, and the more preferred is sodium hydroxide or hydrogen. Potassium oxide. Examples of the acidic compound include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid, and phosphoric acid, or acetic acid, formic acid, acetic acid, methanesulfonic acid, P-toluenesulfonic acid, camphorsulfonic acid, trifluoroacetic acid, and trifluoromethane. Bronsted acids such as sulfonic acids and other organic acids; Bronze acids such as zinc chloride, tin tetrachloride, boron trichloride, boron trifluoride, boron tribromide and the like. -52- 200414902 Furthermore, in the above, mramycin A, mramycin B, mramycin C, mramycin D, mramycin E1, and mlamin In the erythromycin E2, lamycin F, lamycin G, or lamycin Η, the lamycin antibiotics shown in any one of general formula (I) to (ΠI) Mlaminomycin Z 1 or Mlaminomycin Z 2 is obtained by the action of metal alkoxides. In addition, mramycinmycin Z3 or mramycinmycin Z4 can be obtained by the action of a metal alkoxide as shown in formula (IV), which is one of mrammycin I. Examples of the solvent to be used include alcohols such as methanol, ethanol, t-butanol, and tetrahydrofuran. Examples of the alkoxide metal salt include sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide, sodium tert-butoxide, potassium tert-butoxide and the like, and sodium methoxide or sodium ethoxide is preferred. Chromatographic analysis of the obtained laminomycin Z1 or miramycin Z2 using a carrier column such as COSMOSIL (manufactured by Nacalai Tesque); using a carrier such as Diaion CHP-20P (manufactured by Mitsubishi Chemical Corporation) Chromatographic analysis of pipette columns; 5-week chromatographic analysis of colloidal dextran G-10 (manufactured by Amershambiosciences), TOYOPEARLHW40F (manufactured by Toso); DOWEX 50 (manufactured by Nissan Chemical Co., Ltd.) DOWEX 1 (Nissan Chemical Co., Ltd.) Manufactured), DiaionPK2 16 (manufactured by Mitsubishi Chemical Corporation), Diaion PA316 (manufactured by Mitsubishi Chemical Corporation), CM crosslinked dextran C-25 (manufactured by AmerShambi and SCienCes), DEAE parent dextran A-25 (manufactured by Amershambiosciences) ) And other Diai on exchange chromatographic analysis; or can be purified using high-speed liquid chromatographic analysis of cis-layer and reverse-layer columns. -53- 200414902 The above isolation and purification means can be used alone or in a suitable combination, and can be used repeatedly in accordance with occasions to isolate and purify the mrammycin parent material of the present invention. The representative method of manufacturing the mrammycin substance has been described above, but the manufacturing method is not limited thereto, and other manufacturing methods known to those skilled in the art may be used. The present invention further relates to a method for producing a miramycin antibiotic having a desired structure. Regarding the cultivation of the above-mentioned mrammycin-producing bacteria, the desired fatty acid is added to the normal medium, and the general formula (I) to (IV) is preferred, and the general formula (I) is preferred, where R is the corresponding hydrocarbon in the aforementioned fatty acid. The production of chain-type lamminycin antibiotics is increased and produced. The fatty acid to be used has a carbon number of 3 or more without particular limitation, and linear fatty acids, branched fatty acids, saturated fatty acids, unsaturated fatty acids, and the like can be used, and linear saturated fatty acids are preferred. The linear saturated fatty acid has a chain length of 3 or more carbon atoms and is not particularly limited, but is preferably 10 to 20 carbon atoms, more preferably 12 to 18 carbon atoms. For example, when the fatty acid represented by the following general formula (IX) is used, the production will increase. The lamminycin antibiotics are those in the general formula (I) or even (IV) where R = R1,

(IX) 具體而s ’關於當該之方法中，作爲脂肪酸者，使用十 二酸時，一般式⑴乃至（IV)中R爲-(CH2)8CH3之姆拉明黴素 200414902 類抗生素之生產量會增加，脂肪酸中使用十三酸時，一般 式（I)乃至（IV)中R爲-(CH2)9CH3之姆拉明黴素類抗生素之生 產量會增加（最顯著者爲姆拉明黴素B)，脂肪酸使用十四酸 之場合，一般式（I)乃至（IV)中R爲-(CH2)1QCH3之姆拉明黴素 類抗生素之生產量會增加（最顯著者爲姆拉明黴素F)。 又，本發明之上述方法，即具有所冀望構造之姆拉明黴 素類抗生素之製造方法，包含由其製造出之全部姆拉明黴 素類抗生素。 以上所得之本發明化合物，對一般革蘭氏陽性細菌及革 鲁 蘭氏陰性細菌之最少生長抑制濃度（MIC)，可使用普通瓊脂 培養基（營硫化學公司製）或穆勒-因頓納賈瓊脂（Mueller-Hintonagar)培養基（BBL公司製）等，以業者周知之瓊脂平板 稀釋法測定。 又，對於本發明化合物之轉位酵素I之酵素抑制活性，使 用酵素與UDP-N-乙醯基-L-丙胺醯基-r-D-麩胺醯基-m-二胺 基庚二醯基- (Ne-丹醯）-D-丙胺醯基-D-丙胺酸（110?->^ acetylmuramyl-L-Ala-r - D-Glu-m-DAP-(N£-dansyl)-D-Ala- ® D-Ala)及磷酸 '院異戊二燒酯（undecaprenylphosphate)之 反應來測定。 又’對於本發明之化合物之轉位酵素I之酵素抑制活性， 可以業者周知之方法進行測定。 本發明之姆拉明黴素物質，較佳爲姆拉明黴素A、姆拉明 黴素B、姆拉明黴素C、姆拉明黴素D、姆拉明黴素E1、姆 拉明黴素E2、姆拉明黴素F、姆拉明黴素G、姆拉明黴素Η、 -55- 200414902 姆拉明黴素I、姆拉明黴素Z 1或姆拉明黴素Z2、或其藥理學 上容許鹽，可以各種形態投與。其投與形態可列舉例如以 錠劑、膠囊劑、顆粒劑、乳劑、九劑、粉末劑、糖漿劑（液 劑）等經口投與，或注射劑（靜脈內、肌肉內、皮下或腹腔 內投與），點滴劑、栓劑（直腸投與）等之非經口投與。此等 各種製劑，依據習用方法使用主藥製劑化之醫藥製劑技術 領域中通常使用之賦形劑、結合劑、崩解劑、潤滑劑、矯 味矯臭劑、助溶劑、懸浮劑、塗覆劑等。 使用錠劑時，載劑可列舉如使用乳糖、白糖、氯化鈉、 _ 蔔萄糖、尿素、源粉、碳酸鈣、高嶺土、結晶纖維素、石夕 酸等之賦形劑；水、乙醇、丙醇、單糖漿液、葡萄糖液、 澱粉液；明膠溶液、羧甲基纖維素、蟲膠（sheila)、甲基纖 維素、磷酸鉀、聚乙烯吡咯烷等之結合劑；乾燥澱粉、褐 藻酸鈉、瓊脂末、昆布多糖末、碳酸水素鈉、碳酸鈣、聚 氧乙烯山梨糖醇酐脂肪酸酯、月桂基硫酸鈉、硬脂酸單甘 油酯、澱粉、乳糖等之崩解劑；白糖、硬脂酸、可可脂油、 氫添加油等之崩解抑制劑；第4級銨鹽類、月桂基硫酸鈉等 ® 之吸收促進劑；甘油、澱粉等之保濕劑；澱粉、乳糖、高 嶺土、皂土、膠體狀矽酸等之吸著劑；純化滑石、硬脂酸 鹽、硼酸末、聚乙二醇等之潤滑劑等。又，必要時施與所 需通常包覆劑之錠劑，例如可爲糖衣錠、明膠塗覆錠、腸 衣塗覆錠、膜塗覆錠或二層錠、多層錠等。 使用九劑時，作爲載劑體者可使用例如葡萄糖、乳糖、 可可油脂、澱粉、硬化植物油、高嶺土、滑石等之賦形劑； -56- 200414902 ***樹膠末、西黃耆膠末、明膠、乙醇等之結合劑；昆 布多糖瓊脂等之崩解劑等。 使用栓劑時，可廣泛使用作爲載劑之技術領域中習用者’ 可列舉例如聚乙二醇、可可油脂、高級醇、高級醇之酯類、 明膠、半合成甘油酯等。 作爲注射劑使用時，可使用液劑、乳劑或懸滑劑，此等 液劑、乳劑或懸滑劑較佳爲經滅菌、與血液等張，以此等 液劑、乳劑或懸滑劑製造之溶液，只要是醫療用之稀釋劑 皆可使用而未特別限定，特別是可列舉例如水、乙醇、丙 鲁 二醇、乙氧基化異硬脂醯醇、聚氧基化異硬脂醯醇、聚氧 乙烯山梨糖醇酐脂肪酸酯。又，此時，調製等張性溶液中 可於製劑中含有充分量之食鹽、葡萄糖或甘油，或習用之 溶解補助劑、緩衝劑、無痛劑等。 又，上述製劑中，必要時可含有著色劑、保存劑、香料、 風味劑、甘味劑等，再者，可含有其它醫藥品。 上述製劑中所含有效成分化合物之量未特別限定，可於 廣範圍中適宜選擇，但通常爲全部組成物中1至70重量％， · 較佳爲含有1至3 0重量％。 使用量會依症狀、年齡、體重、投與方法及劑形等而異， 但通常相對應於症狀，成人中1日之上限爲2000mg(較佳爲 100mg)，下限爲0.1mg(較佳爲lmg，更佳者爲l〇mg)，可一 曰1回或分成數回投與。 【實施方式】 [產業上之利用可能性] -57- 200414902 由以上之結果，本發明化合物群係爲包含革蘭氏陽性菌 之各種細菌感染症之預防藥或治療藥，及以各種細菌感染 症之預防藥或治療藥爲目的，作爲使用有機化學及微生物 變換之衍生物之合成原料上爲有用的。 [發明之實施中之最佳形態] 以下中以實施例具體說明本發明，但無意以此限制本發 明之範疇於此。 [實施例] (實施例1)鏈孢囊菌屬3人1^反6()501株之培養 (1 ) 一次培養 斜面培養基上中生長之SANK6050 1株，添加滅菌水， 使用白金圈取菌絲，均質化此菌絲懸濁液後，以下列記 載組成之前培養培養基5 00 ml加入7瓶2L之三角燒瓶（種 燒瓶）中，無菌接種，其次將該燒瓶於Caudalie震盪機中 28°C、210rpm，8日間震盪培養，進行一次前培養。 前培養之培養基 [表4] 葡萄糖 30g 生酵母菌 l〇g 大豆粉 30g CaC03 4g MgS04.7H20 2g 消泡劑（CB442) 1 0 m g 自來水 1000ml -58- 200414902 滅菌前之pH値爲7.2 滅菌，121°C 30分鐘滅菌。 (2 )二次培養 以該一次前培養液，經滅菌之上記組成之前培養培養基 30L放入60L容量槽培養機2中於5%(V/V)植菌，溫度28°C， 通氣量lvvm，旋轉數次數爲1〇〇至2〇〇 rpm，溶液含氧量爲 5.0ppm，於2日間二次前培養。 (3 )本培養 滅菌下述組成之本培養培養基，400L放入600L容器培養 機2基中二次前培養液以5%(V/V)植菌，溫度28°C，通氣量 lvvm，旋轉次數83至200rpm，溶液含氧量5.0ppm，以11日 間培養。 本培養培養基 [表5] 可溶性澱粉 7〇g Pharmamedia 3〇g C.S.L. 5g CaC03 4g MgS04-7H20 2g 消泡劑（CB442) 1 Oir 自來水 1000ml 滅菌前之pH値爲7.2 滅菌，121°C 30分鐘滅菌。 (實施例2)姆拉明黴素A、姆拉明黴素B、姆拉明黴素C、姆 -59- 200414902 拉明黴素D、姆拉明黴素E1、姆拉明黴素E2、姆拉明黴素之 粗粉末之分離 以下之純化中，以下列高速液體色層分析（Η P L C)監測活 性成分。(IX) Specifically, s' Regarding the production of mulamycin 200414902 antibiotics of general formula (i) and (IV) in which R is-(CH2) 8CH3 when dodecanoic acid is used as the fatty acid in the method. The amount will increase. When tridecanoic acid is used in the fatty acid, the production of mrammycin antibiotics with R of-(CH2) 9CH3 in general formula (I) or (IV) will increase (the most significant is mrammin In the case of mycol B), myristic acid is used for fatty acid, the production of mrammycin antibiotics with R of-(CH2) 1QCH3 in general formula (I) or (IV) will increase (the most significant is mla Methromycin F). The above-mentioned method of the present invention, that is, a method for producing a lamycin antibiotic having a desired structure, includes all the lamycin antibiotics produced therefrom. The minimum growth inhibitory concentration (MIC) of the compound of the present invention obtained above for general Gram-positive bacteria and Gram-negative bacteria can be ordinary agar medium (manufactured by Ying sulfur Chemical Co., Ltd.) or Muller-Intonagia Agar (Mueller-Hintonagar) medium (manufactured by BBL) and the like were measured by an agar plate dilution method known to those skilled in the art. For the enzyme inhibitory activity of the translocation enzyme I of the compound of the present invention, an enzyme and UDP-N-ethylamyl-L-propylaminofluorenyl-rD-glutaminyl-m-diaminoheptanyl- (Ne-Danyl) -D-Alaninyl-D-Alanine (110?-≫ ^ acetylmuramyl-L-Ala-r-D-Glu-m-DAP- (N £ -dansyl) -D-Ala -® D-Ala) and undecaprenyl phosphate. The enzyme inhibitory activity of the translocation enzyme I of the compound of the present invention can be measured by a method known to a person skilled in the art. The lamycinin substance of the present invention is preferably lamycin A, lamycin B, lamycin C, lamycin D, lamycin E1, and lamycin Doxorubicin E2, Mrimycin F, Mramycin G, Mramycin Η, -55- 200414902 Mramycin I, Mramycin Z 1 or Mramycin Z2 or a pharmacologically acceptable salt thereof can be administered in various forms. Examples of the administration form include oral administration in the form of tablets, capsules, granules, emulsions, nine doses, powders, syrups (liquids), or injections (intravenous, intramuscular, subcutaneous or intraperitoneal). Administration), parenteral administration of drips, suppositories (rectal administration), etc. These various preparations are excipients, binding agents, disintegrating agents, lubricants, flavoring and correcting agents, co-solvents, suspending agents, coating agents, etc. that are generally used in the technical field of pharmaceutical preparations formulated with the main drug according to conventional methods. . When using lozenges, the carriers include, for example, excipients such as lactose, white sugar, sodium chloride, glucose, urea, source powder, calcium carbonate, kaolin, crystalline cellulose, and oxalic acid; water, ethanol , Propanol, monosaccharide syrup, glucose solution, starch solution; gelatin solution, carboxymethyl cellulose, sheila, methyl cellulose, potassium phosphate, polyvinylpyrrolidine and other binding agents; dried starch, brown algae Disintegrating agent for sodium, agar, konbu polysaccharide, sodium bicarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid ester, sodium lauryl sulfate, monoglyceryl stearate, starch, lactose, etc .; white sugar , Stearic acid, cocoa butter oil, hydrogen addition oil, etc .; disintegration inhibitors; absorption enhancers of grade 4 ammonium salts, sodium lauryl sulfate, etc .; humectants such as glycerin, starch; starch, lactose, kaolin, Sorbent, colloidal silicic acid and other sorbents; lubricants such as purified talc, stearate, ground borate, polyethylene glycol, etc. In addition, if necessary, a tablet that is usually coated with a desired coating agent may be, for example, a sugar-coated tablet, a gelatin-coated tablet, an enteric-coated tablet, a film-coated tablet, a two-layer tablet, or a multi-layer tablet. When using nine doses, as a carrier, excipients such as glucose, lactose, cocoa butter, starch, hardened vegetable oil, kaolin, talc, etc. can be used; -56- 200414902 gum arabic, tragacanth gum, gelatin, Binding agent such as ethanol; disintegrating agent such as konbu polysaccharide agar. When a suppository is used, it can be widely used as a carrier in the technical field. Examples include polyethylene glycol, cocoa butter, higher alcohols, higher alcohol esters, gelatin, and semi-synthetic glycerides. When used as an injection, liquids, emulsions, or suspensions can be used. These liquids, emulsions, or suspensions are preferably sterilized and areotonic with blood. The solution is not particularly limited as long as it is a diluent for medical use. In particular, examples thereof include water, ethanol, proprudiol, ethoxylated isostearyl alcohol, and polyoxylated isostearyl alcohol. 2. Polyoxyethylene sorbitan fatty acid ester. In this case, in the preparation of the isotonic solution, a sufficient amount of common salt, glucose or glycerin, or conventional dissolution aids, buffers, analgesics, etc. may be contained in the preparation. Moreover, the said formulation may contain a coloring agent, a preservative, a fragrance | flavor, a flavoring agent, a sweetener, etc. as needed, and may contain other pharmaceuticals. The amount of the active ingredient compound contained in the above formulation is not particularly limited and can be appropriately selected from a wide range, but it is usually 1 to 70% by weight, and preferably 1 to 30% by weight of the total composition. The amount used will vary depending on symptoms, age, weight, method of administration and dosage form, but usually corresponds to the symptoms. The upper limit for adults per day is 2000 mg (preferably 100 mg) and the lower limit is 0.1 mg (preferably lmg, more preferably 10mg), can be administered once or divided into several times. [Embodiment] [Industrial Applicability] -57- 200414902 From the above results, the compound group of the present invention is a preventive or therapeutic agent for various bacterial infections including Gram-positive bacteria, and infection with various bacteria It is useful as a preventive or therapeutic agent for diseases, and is useful as a synthetic raw material using derivatives of organic chemistry and microbial conversion. [Best Mode in the Implementation of the Invention] The present invention will be specifically described below by way of examples, but it is not intended to limit the scope of the present invention to this. [Example] (Example 1) Cultivation of 3 human 1 ^ trans 6 () 501 strains of Streptococcus genus (1) One strain of SANK6050 grown on slanted medium in a single culture, sterilized water was added, and bacteria were collected using a platinum ring After the mycelium suspension was homogenized, 500 ml of the culture medium before the composition described below was added to 7 2L Erlenmeyer flasks (seed flasks), aseptically inoculated, and then the flasks were placed in a Caudalie shaker at 28 ° C. At 210 rpm, shake culture was performed for 8 days, and one pre-culture was performed. Pre-cultivation medium [Table 4] 30g glucose, 10g yeast, 10g soybean powder, 30g CaC03, 4g MgS04.7H20, 2g defoaming agent (CB442), 10 mg tap water, 1000ml -58- 200414902, 7.2 sterilization before sterilization, 121 ° C for 30 minutes. (2) The secondary culture is based on the primary culture medium, and 30L of the culture medium before the composition is sterilized. The culture medium is placed in a 60L capacity tank incubator 2 in a 5% (V / V) plant, the temperature is 28 ° C, and the ventilation volume is lvvm. , The number of rotations is 100 to 2000 rpm, the solution oxygen content is 5.0 ppm, and the cells are cultured twice before 2 days. (3) This culture sterilizes this culture medium with the following composition. 400L is put into 2 bases of a 600L container culture machine. The secondary pre-culture solution is planted with 5% (V / V), the temperature is 28 ° C, the ventilation volume is lvvm, and it is rotated. The number of times was 83 to 200 rpm, and the solution had an oxygen content of 5.0 ppm, and was cultured in 11 days. This culture medium [Table 5] Soluble starch 70g Pharmamedia 30g C.S.L. 5g CaC03 4g MgS04-7H20 2g Defoamer (CB442) 1 Oir Tap water 1000ml pH sterilization before sterilization is 7.2 sterilization at 121 ° C for 30 minutes. (Example 2) Mramingomycin A, Mramingomycin B, Mramingmycin C, M-59-200414902 laminmycin D, Mlaminomycin E1, Mlaminomycin E2 2. Isolation of the crude powder of mrammycin In the following purification, the active ingredients were monitored by the following high-speed liquid chromatography (ΗPLC).

(i)姆拉明黴素A、姆拉明黴素Β、姆拉明黴素C、姆拉明黴 素D 管柱： CAPCELL PAK C18UG120 4.60x150mm(資生堂股份有限公司製） 溶劑： 含10mM重碳酸銨之40%乙腈水溶液 流速： 1 .Oml/分鐘 檢出： 紫外光吸收2 6 0 n m 保持時間： 9·3分鐘（姆拉明黴素A) 9·8分鐘（姆拉明黴素B) 1〇·9分鐘（姆拉明黴素C) 14.8分鐘（姆拉明黴素D) (ii)姆拉明黴素E1、姆拉明黴素E2、姆拉明黴素F 管柱： CAPCELL PAK C18UG120 4.6 0 X 150mm(資生堂股份有限公司製） 溶劑： 含10m Μ重碳酸銨之42 %乙腈水溶液 流速： 1 .Oml/分鐘 檢出： 紫外光吸收260nm 保持時間： 9.5分鐘（姆拉明黴素El) 1〇·2分鐘（姆拉明黴素E2) 1 1.2分鐘（姆拉明黴素F) -60- 200414902 (l)混合粗粉末之提取 實施例1所得之培養終了液（800 L)中添加水，稀釋爲 9 0 0L，稀釋液中加入乙腈1 8 00 L後，添加助過濾劑矽藻土 (Celite)545 (45.4kg)，以壓力過濾器過濾，將所得到之溶液 及洗液合倂（2810L)並減壓濃縮後，加入水（ 1 400L)稀釋，放 入以水平衡之DiaionHP20管柱（110L)中，管柱以水（400L)及 30%乙腈水溶液（400L)洗滌後，以50%乙腈水溶液（400L)將 活性物質洗析出，減壓濃縮此洗析液後，冷凍乾燥得到粗 粉末（129g)。 將此粗粉末懸浮於含有〇·〇2 %三氟乙酸之30%乙腈水溶液 (3L)，供給於以相同溶劑系平衡之Diaion CHP20P管柱中 (50L)，以30%乙腈水溶液（150L)洗滌後，進行依次以40%乙 腈水溶液（150L)及50%乙腈水溶液（150L)洗析活性物質，將 40%乙腈水溶液及50%乙腈水溶液溶出之部分個別減壓濃縮 後冷凍乾燥，40%乙腈水溶液溶出之部分得到粗粉末36.5g， 5 0%乙腈水溶液溶出之部分得到粗粉末17.3g。 接著，將50%乙腈水溶液溶出之部分所得粗粉末17.3g懸 浮於甲醇500ml中，放入TOYOPEARLHW-40F管柱（2L)中， 以相同溶劑展開。 洗析液以每5 0 0 m 1劃分各部分，收集濾分8至1 1，減壓濃 縮得到粗粉末6.2g，將此粗粉末溶解於甲醇（l〇〇ml)中，將 其中之50ml供給於以含10mM重碳酸銨之45%乙腈水溶液平 衡 HPLC管柱（YMC Pack)ODS-20AM，l〇〇0x 500mm)中。管 柱以流速220ml/分鐘展開，目的物質於2 6 0nm紫外光吸收檢 200414902 出，保持時間1 9.2分鐘至2 3 · 8分鐘洗析之部分’ 2 3 · 8分鐘至 26.8分鐘之部分及26.8分鐘至30.0分鐘之洗析部分分2次分 別取得，2次分別取得相同保持時間之部分，將各部分分別 減壓濃縮後，冷凍乾燥，保持時間19.2分鐘至23.8分鐘洗析 出之部分得到含姆拉明黴素A、姆拉明黴素B及姆拉明黴素 €之粗粉末1(48611^)，23.8分鐘至26.8分鐘洗析出之部分含 姆拉明黴素D、姆拉明黴素E1及姆拉明黴素E2之粗粉末 2(199mg)，26.8分鐘至30.0分鐘洗析出之部分含姆拉明黴素 F之粗粉末F(445mg)。 (2)姆拉明黴素A、姆拉明黴素B及姆拉明黴素C之分離 將上述粗粉末1溶解甲醇（3〇ml)中，將其中之3 00 // 1供給 於經含10mM重碳酸銨之40%乙腈水溶液平衡之HPLC管柱 (CAPCELL PAK C18UG120，2〇 0 x 250mm)中。管柱以流速 l(KOml/分鐘展開，於260nm之紫外光吸收檢出目的物質， 於保持時間21.1分鐘析出之部分、22.6分鐘析出之部分及 24.6分鐘析出部分分成100回取得，合倂相同保持時間所得 之部分，將各部分分別減壓濃縮後冷凍乾燥，保持時間2 1 . 1 分鐘洗析之部分得到含有姆拉明黴素A之粗粉末 八（25.1111§)，24.6分鐘洗析之部分含有姆拉明黴素（：之粗粉 末0(42.511^)。又，22.6分鐘洗析之部分之冷凍乾燥粗粉末 (88.0m9)再溶解於甲醇（5ml)中，其中之80//1供給於含有 10mM甲酸銨之44.4%乙腈水溶液平衡之^^1^管柱〇6¥61〇811 030-1；0-5,20(^15〇111111)中。管柱以流速1〇.〇1111/分鐘展開， 於26 Onm紫外光吸收檢出目的物質，保持時間21.1分鐘洗析 200414902 之部分分成62回分次收取，得到相同保持時間之部分，經 減壓濃縮後冷凍乾燥，得到含姆拉明黴素B之粗粉末 B(29.9mg) 〇 (3)姆拉明黴素D、姆拉明黴素E1及姆拉明黴素E2之分離 將上述粗粉末2溶解於甲醇（15ml)中，將其中3 00 // 1供給 於經含10mM甲酸銨之48.4%乙腈水溶液平衡之HP LC管柱 (Develosil C30-UG-5，2〇0x 150mm)。管柱以流速 10.0ml/ 分鐘展開，於26 Onm之紫外光吸收檢出目的物質，保持時間 19.0分鐘洗析之濾分及20.1分鐘洗析之部分分成50次分次收 φ 取。將保持時間20.1分鐘洗析之部分經減壓濃縮後，冷凍 乾燥，得到含姆拉明黴素E2之粗粉末E2 (29.7mg)。又，將19.0 分鐘洗析之部分合倂並減壓濃縮後，冷凍乾燥得到粗粉末 (85mg)，再溶解於甲醇（5ml)，將其中80 // 1供給於經含10mM 重碳酸銨之42%乙腈水溶液平衡之1^1^管柱（€八？€£1^?八：^ C18UG120, 2O0X 250mm)中。管柱以流速10.0ml/分鐘展開， 於260nm之紫外光吸收檢出目的物質，保持時間23.4分鐘洗 析部分及24.5分鐘洗析之部分分成62次分次收取，所得相 鲁 同保持時間之濾分經減壓濃縮後，冷凍乾燥，保持時間23.4 分鐘洗析之部分得到含姆拉明黴素D之粗粉末D(11.2mg)。 一方面，24.5分鐘洗析之部分減壓濃縮後，凍結乾燥得到 粗粉末（22.7mg)再溶解於甲醇（2 ml)，將其中80 // 1供給於經 含10mM甲酸銨42.8%乙腈水溶液HPLC管柱（DevelosilC30-UG-5,2O0x 150mm)。管柱以流速10.0ml/分鐘展開，於260nm 紫外光吸收檢出目的物質，保持時間19· 9分鐘洗析之部分 -63- 200414902 分成25回分次收取。得到之相同保持時間之部分，經減壓 濃縮後冷凍乾燥，得到姆拉明黴素E1之粗粉末El(13.3mg)° (實施例3)姆拉明黴素A之純化 將含上述姆拉明黴素A之粗粉末A (2 5.1m g)溶解於甲醇 (2ml)中，將其中80/zl供給於經含10mM甲酸銨之42.8%乙腈 水溶液平衡之 HPLC 管柱（DevelosilC3O-UG-5,2O0x 150mm) 中，管柱以流速10.〇ml/分鐘展開，260nm之紫外光吸收檢 出目的物質，保持時間22.4分鐘洗析之部分以25回分次收 取，將所得相同保持時間之部分，減壓濃縮後，冷凍乾燥’ 得到姆拉明黴素A(12.4mg)之無色粉末。 (實施例4)姆拉明黴素B之純化 將含上述姆拉明黴素B之粗粉末B ( 29.9mg)溶解於甲醇 (2ml)，將其中80 // 1供給於經含10mM甲酸銨之42%乙腈水溶 液平衡之 HPLC管柱（Develosil C30-UG-5，20 0 X 1 50mm)中， 管柱以流速10.Ornl/分鐘展開，260nm之紫外光吸收檢出目 的物質，保持時間18.3分鐘洗析之部分以25回分次收取， 將所得相同保持時間之部分，減壓濃縮後，冷凍乾燥，得 到姆拉明黴素B(13.7mg)之無色粉末。 (實施例5)姆拉明黴素C之純化 將含上述姆拉明黴素C之粗粉末B ( 42.5mg)溶解於甲醇 (3ml)，將其中80 # 1供給於經含10mM甲酸銨之42.8%乙腈水 溶液平衡之 HPLC 管柱（Develosil C30-UG-5，2〇0x 150mm) 中，管柱以流速10.0ml/分鐘展開，260nm之紫外光吸收檢 出目的物質，保持時間22.3分鐘洗析之部分以37回分次收 -64- 200414902 取，將所得相同保持時間之部分，減壓濃縮後，冷凍乾燥， 得到姆拉明黴素C(12.7mg)之無色粉末。 (貫施例6 )姆拉明徽素D之純化 將含上述姆拉明黴素D之粗粉末D ( 1 1 .2mg )溶解於甲醇 (lml)，將其中80 // 1供給於經含1 OmM甲酸銨之42%乙腈水溶 液平衡之 HPLC 管柱（CAPCELLPAKC18UG12O,2O0x 250mm) 中，管柱以流速ΙΟ.ΟπιΙ/分鐘展開，2 60nm之紫外光吸收檢 出目的物質，保持時間20.6分鐘洗析之部分以12回分次收 取，將所得相同保持時間之部分，減壓濃縮後，冷凍乾燥’ 得到姆拉明黴素D(9.0mg)之無色粉末。 (實施例7 )姆拉明黴素E 1之純化 將含上述姆拉明黴素E 1之粗粉末E 1 ( 1 3.3 mg )溶解於甲 醇（lml)，將其中80 /z 1供給於經含10mM甲酸銨之40%乙腈水 溶液平衡之 HPLC 管柱（CAPCELL PAK C18UG120，2〇θχ 25〇111111)中，管柱以流速10.〇1111/分鐘展開，26〇11111之紫外光 吸收檢出目的物質，保持時間21.7分鐘洗析之部分以12回 分次收取，將所得相同保持時間之部分，減壓濃縮後，冷 凍乾燥，得到姆拉明黴素El(10.3mg)之無色粉末。 (實施例8)姆拉明黴素E2之純化 將含上述姆拉明黴素E2之粗粉末E2(29.7mg)溶解於甲 醇（21111)，將其中80//1供給於經含1〇111^1甲酸銨之47.6%乙膪 水溶液平衡之 HPLC 管柱（DevelosilC30-UG-5,20(/)X 150mm) 中，管柱以流速10.0ml/分鐘展開，2 60nm之紫外光吸收檢 出目的物質，保持時間1 8.3分鐘洗析之部分以2 5回分次收 -65- 200414902 取，將所得相同保持時間之部分，減壓濃縮後’冷凍乾燥’ 得到姆拉明黴素E2(19.0mg)之無色粉末。 (實施例9)姆拉明黴素F之純化 將含上述姆拉明黴素F之粗粉末F( 445mg)中之l〇〇mg溶 解於甲醇（6ml)，將其中80 // 1供給於經含1 OmM重碳酸銨之 40%乙腈水溶液平衡之HPLC管柱（Develosil C30-UG-5，20 0x 150mm)中，管柱以流速l〇.〇ml/分鐘展開，260nm之紫外 光吸收檢出目的物質’保持時間2 1 · 1分鐘洗析之部分以7 5 回分次收取，將所得相同保持時間之部分’減壓濃縮後’ 冷凍乾燥，得到姆拉明黴素F(57.7mg)之無色粉末。 (實施例10)姆拉明黴素Z1及姆拉明黴素Z2之取得及純化 關於以下之純化，係活性濾分已下列高速液體色層分析 (HPLC)監測。 ⑴姆拉明黴素Z1 管柱： CAPCELL PAKC18UG120 4.60X l5〇mm (資生堂股份有限公司製） 溶劑 10mM重碳酸銨水溶液 流速 1 . 0 m 1 /分鐘 檢出 紫外光吸收260nm 保持時間：9.2分鐘 (ii)姆拉明黴素Z2 CAPCELL PAKC18UG120 4.6 (/) X 150mm (資生堂股份有限公司製） 溶劑： 含有10mM重碳酸銨水之3%乙腈水溶液 200414902 流速： 1 . 0 m 1 /分鐘 檢出： 紫外光吸收2 6 0 n m 保持時間：1 3.0分鐘 管柱：CAPCELL PAK C18UG120 將以實施例9所得到之姆拉明黴素F( 8 Omg)溶解於含有 〇·2Ν氫氧化鈉之50%甲醇水（10ml)中，攪拌6小時。以鹽酸 中和後，減壓濃縮，餾去甲醇。將此濃縮液以乙酸乙酯（5m 1 ) 洗滌2次後，冷凍乾燥。所得之粗粉末溶解於1〇mM重碳酸 銨水溶液（2ml)，將其中100//1供給於經含10mM重碳酸銨水 ^itzFfj^HPLCl;ft(CAPCELLPAKC18UG12〇J 20 φχ 2 5 Omm)中。於23分鐘洗析出之溶劑於含l〇mM重碳酸銨之5% 乙腈水溶液等之管柱以流速10.Oml/分展開，於260nm紫外 光吸收檢出目的物質，保持時間16.0分鐘洗析出之部分及 2 1.9分鐘洗析出之部分分20回分次收取。將相同保持時間 鐘洗析出之部分合倂，分別減壓濃縮後冷凍乾燥，將保持 時間1 6 · 0分鐘洗析出之部分得到爲無色粉末之姆拉明黴素 冗1(11.8111§)，保持時間21.9分鐘洗析出部分得到爲無色粉末 姆拉明黴素Z2(5.8mg)。 (試驗例1 )抗菌活性之測定（抗革蘭氏陽性菌活性） 本發明之姆拉明黴素A、姆拉明黴素B、姆拉明黴素C、 姆拉明黴素D、姆拉明黴素E1、姆拉明黴素E2、姆拉明黴素 F、姆拉明黴素Z1及姆拉明黴素Z 2對於黃色葡萄球菌 (Staphylococcus aureus)FDA2 09P JC-1 株（以下略稱爲對於 黃色葡萄球菌2 09 P株）及枯草桿菌（Bacillus -67- 200414902 subtilis)ATCC6633株（以下略稱爲枯草桿菌6633株）之最小 生長抑制濃度（MIC)之測定係以下列方法進行。檢體水溶液 以l〇〇〇//g/ml之濃度作2倍稀釋，調製14次階段（ 1 000 # g/ml、500//g/ml、250//g/ml、125/zg/ml、62.5//g/ml、31·3 //g/ml> 15.6//g/mL· 7.8//g/mL· 3.9/ig/mL· 2//g/mL· l//g/ml ^ 〇.5//g/ml、0.24//g/ml、〇.12//g/ml)之稀釋液。各稀釋液於 圓形 Petri disd(9〇0x 20mm，Terumo 公司製）中分注 lml 後， 加入9ml穆勒-因頓納賈瓊脂培養基（BBL公司製）混合，作成 平板。被檢菌黃色葡萄球菌2 09 P株及枯草桿菌6 6 3 3株於胰 蛋白酶酪蛋白腺肉汁培養基（T SB)培養基（榮硏化學公司製） 中3 7°C前一夜培養。試驗當日，所得菌液使用TSB稀釋100 倍’以1白金圈之菌塗抹平板培養基兩線塗抹。此兩線塗抹 之平板培養基於3 7 °C培養1 8小時後，判定ΜIC。 試驗化合物 被檢菌：黃色葡萄球菌 枯草桿菌 姆拉明黴素A 25 25 姆拉明黴素B 6.25 6.25 姆拉明黴素C 25 6.25 姆拉明黴素D 6.25 6.25 姆拉明黴素E 1 6.25 6.25 姆拉明黴素E 2 6.25 6.25 姆拉明黴素F 6.25 6.25 [表6]抗菌活性（抗革蘭氏陽性菌活性） _ MIC ( β g/ml ) -68- 200414902 由以上結果，顯示出姆拉明黴素A、姆拉明黴素B、姆拉 明黴素C、姆拉明黴素D、姆拉明黴素E1、姆拉明黴素E2及 姆拉明黴素F對黃色葡萄球菌209 P株及枯草桿菌66 3 3株具有 抗菌活性。 (試驗例2)轉位酵素I酵素抑制活性之測定 本發明之各化合物對轉位酵素I之酵素抑制活性，使用酵 素與UDP-N -乙醯基-L-丙胺醯基-r-D-麩胺醯基-m-二胺基庚 二醯基- (Νε-丹醯）-D-丙胺醯基-D-丙胺酸（110?-1^-acetylixiurainyl-L-Ala - 7 - D- Glu-m-DAP-(N ε - dansyl)-D-Ala_ D-Ala)及憐酸 --院異戊二儲酯（undecaprenylphosphate)之 反應來測定。 即’將含編碼轉位酵素I之質體之大腸菌E.C〇li/pTA5株培 養所得菌體於T r i s鹽酸緩衝液（p Η 8 · 0 )中以超音波震碎後， 將粗提取液離心，得到之沉澱以界面活性化劑溶化之溶液 作爲酵素源來使用’ UDP-N-乙醯基-L-丙胺醯基-r-D-魅胺 醯基-m-二胺基庚二醯基-(Νε_丹醯广卜丙胺醯基-D_丙胺酸 及磷酸十一烷異戊二烯酯與酵素液培育後，酵素反應所增 加之螢光度’以激發波長3 5 5 nm，檢出波長5 3 8 nm之條件定 量爲酵素活性，50%酵素抑制濃度（IC5。）由同時添加抑制劑 之濃度計算出抑制率而求出。 [表7]轉位酵素I抑制活性_ g式驗化合物 IC 5 Q ( // g / m 1) 姆拉明黴素A 0.0105 姆拉明黴素B 0.0068 -69- 200414902 姆拉明黴素c 0, ,0 104 姆拉明黴素D 0, .00 9 9 姆拉明黴素El 〇( .0115 姆拉明黴素E2 0, .0 109 姆拉明黴素F 0, .00 8 9 姆拉明黴素Z 1 0 • 03 13 姆拉明黴素Z2 0 .125 姆拉明黴素A、姆拉明黴素B、姆拉明黴素C、姆拉明黴 素D、姆拉明黴素E 1、姆拉明黴素E2、姆拉明黴素F、姆拉 明黴素Z 1及姆拉明黴素Z2對轉位酵素I顯示出有抑制活性。 (實施例1 1)SANK6050 1株之十四酸添加培養 (1 )前培養 在斜面培養基上生長之SANK6050 1株，以白金圈取之 1 · 5 c m角落之菌絲片，將此菌絲片於生理食鹽水均質化之均 質物，將下表8中記載之組成之前培養培養基80ml放入500ml 容量之1個三角燒瓶（種燒瓶）中’無菌接種’其次將該燒 瓶於Caudalie震盪機中，28°C，21〇rpm震盪培養6日，進行 一次前培養。 [表8]前培養培養基Τ -1 2培養基_ 葡萄糖 3()g 生酵母菌 lQg 大豆粉 3()g(i) Mramingomycin A, Mramingomycin B, Mramingomycin C, Mramingomycin D column: CAPCELL PAK C18UG120 4.60x150mm (made by Shiseido Co., Ltd.) Solvent: Contains 10 mM weight 40% acetonitrile aqueous solution of ammonium carbonate Flow rate: 1.0 ml / min Detection: UV light absorption 2 60 nm Holding time: 9.3 minutes (mramingin A) 9 · 8 minutes (mramingin B ) 10.9 minutes (Mramingin C) 14.8 minutes (Mramingin D) (ii) Mramingin E1, Mramingin E2, Mramingin F column: CAPCELL PAK C18UG120 4.6 0 X 150mm (manufactured by Shiseido Co., Ltd.) Solvent: 42% acetonitrile aqueous solution containing 10m M ammonium bicarbonate Flow rate: 1.0ml / min Detection: UV light absorption 260nm Holding time: 9.5min (Muramin Erythromycin El) 10.2 minutes (Mramingin E2) 1 1.2 minutes (Mramingin F) -60- 200414902 (l) Extraction of mixed crude powder The culture end liquid obtained in Example 1 (800 L) Water was added and diluted to 900 L. After adding 1 800 L of acetonitrile to the diluted solution, filter aid Celite 545 (45.4 kg) was added under pressure. Filter through a filter, combine the obtained solution and washing solution (2810L) and concentrate under reduced pressure, add water (1 400L) to dilute, and place into a DiaionHP20 column (110L) equilibrated with water, and the column with water (400L) ) And 30% acetonitrile aqueous solution (400L), the active material was washed out with 50% acetonitrile aqueous solution (400L), the washing solution was concentrated under reduced pressure, and freeze-dried to obtain a crude powder (129g). This crude powder was suspended in a 30% acetonitrile aqueous solution (3L) containing 0.02% trifluoroacetic acid, supplied to a Diaion CHP20P column (50L) equilibrated with the same solvent system, and washed with a 30% acetonitrile aqueous solution (150L). After that, the active substance was washed with 40% acetonitrile aqueous solution (150L) and 50% acetonitrile aqueous solution (150L) in that order, and the portions dissolved in the 40% acetonitrile aqueous solution and the 50% acetonitrile aqueous solution were individually concentrated under reduced pressure, and then freeze-dried. The 40% acetonitrile aqueous solution was then dried. The dissolved portion was 36.5 g of a coarse powder, and the dissolved portion of 50% acetonitrile aqueous solution was 17.3 g of a coarse powder. Next, 17.3 g of the crude powder obtained by dissolving a 50% acetonitrile aqueous solution was suspended in 500 ml of methanol, placed in a TOYOPEARLHW-40F column (2L), and developed with the same solvent. The eluate was divided into 5 parts per 500 m1, and the fractions 8 to 11 were collected, and concentrated under reduced pressure to obtain a crude powder 6.2 g. This crude powder was dissolved in methanol (100 ml), and 50 ml of the powder was dissolved. It was supplied to an equilibration HPLC column (YMC Pack) ODS-20AM (1000x 500 mm) with a 45% acetonitrile aqueous solution containing 10 mM ammonium bicarbonate. The column was developed at a flow rate of 220 ml / min, and the target substance was detected at 2,600 nm UV absorption test 200414902. The holding time was from 19.2 minutes to 2 3 · 8 minutes, and the portion was washed out. 2 3 · 8 minutes to 26.8 minutes, and 26.8 minutes. The fractions from 3 minutes to 30.0 minutes were obtained in 2 separate portions, and the portions with the same retention time were obtained twice. Each portion was concentrated under reduced pressure, and then freeze-dried. The fractions that were washed out and retained for 19.2 minutes to 23.8 minutes were obtained. Ramimycin A, Mramycin B and Mramycin B (1,48611 ^), 23.8 minutes to 26.8 minutes of the washed powder containing Mramycin D, Mramycin Coarse powder 2 (199 mg) of E1 and mlaminomycin E2, and washed out part of the crude powder F (445 mg) containing mlaminin F from 26.8 minutes to 30.0 minutes. (2) Separation of mrammycin A, mrammycin B and mrammycin C The above crude powder 1 was dissolved in methanol (30 ml), and 3 00 // 1 of them was supplied to An HPLC column (CAPCELL PAK C18UG120, 200 x 250 mm) equilibrated with a 40% acetonitrile aqueous solution containing 10 mM ammonium bicarbonate. The column was developed at a flow rate of 1 ml / min, and the target substance was detected at 260 nm by ultraviolet light absorption. The portion precipitated at the retention time of 21.1 minutes, the portion precipitated at 22.6 minutes, and the precipitated portion at 24.6 minutes were divided into 100 times. The part obtained by time, each part was concentrated under reduced pressure, and then freeze-dried. The part that was washed for a period of time of 21.1 minutes was obtained to obtain a crude powder containing mlaminomycin A (25.1111§), and the part was washed for 24.6 minutes. Contains mramycin (: of the coarse powder 0 (42.511 ^). In addition, a portion of the freeze-dried coarse powder (88.0m9) washed out in 22.6 minutes was redissolved in methanol (5ml), of which 80 // 1 was supplied In a 44.4% acetonitrile aqueous solution column equilibrated with 10 mM ammonium formate in a ^^ 1 ^ column 〇6 ¥ 61〇811 030-1; 0-5,20 (^ 15〇111111). The column was at a flow rate of 10.0111 Expansion per minute, the target substance was detected at 26 Onm UV light absorption, the holding time was 21.1 minutes, the portion of 200414902 was washed and divided into 62 times, and the portion with the same holding time was obtained. After being concentrated under reduced pressure, it was freeze-dried to obtain mramine. Coarse powder B (29.9mg) of oxytetracycline B Separation of Peptide D, Mlaminycin E1 and Mlaminycin E2 The above coarse powder 2 was dissolved in methanol (15ml), and 3 00 // 1 of it was supplied to a 48.4% acetonitrile aqueous solution containing 10 mM ammonium formate. Equilibrated HP LC column (Develosil C30-UG-5, 2000x 150mm). The column was developed at a flow rate of 10.0ml / min. The target substance was detected at 26 Onm UV light absorption, and the retention time was 19.0 minutes. The fractions washed and separated for 20.1 minutes were divided into 50 fractions and collected φ. The fractions washed and separated for a holding time of 20.1 minutes were concentrated under reduced pressure, and then freeze-dried to obtain a crude powder E2 (29.7 mg) In addition, the fractions washed and analyzed for 19.0 minutes were combined and concentrated under reduced pressure, and then freeze-dried to obtain a coarse powder (85 mg), which was redissolved in methanol (5 ml), and 80/1 of this was supplied to a solution containing 10 mM ammonium bicarbonate. A 42% acetonitrile aqueous solution was equilibrated in a 1 ^ 1 ^ column (€ 8? € £ 1 ^? 8: ^ C18UG120, 2O0X 250mm). The column was developed at a flow rate of 10.0ml / min, and it was detected at 260nm by ultraviolet light absorption. For the target substance, the holding time of 23.4 minutes and the washing portion of 24.5 minutes were divided into 62 fractions and collected. The fractions with the same retention time were concentrated under reduced pressure, freeze-dried, and the fractions with the retention time of 23.4 minutes were washed to obtain the crude powder D (11.2 mg) containing mlaminomycin D. On the one hand, the fractions that were washed and analyzed at 24.5 minutes were reduced. After concentrating under pressure, freeze-drying to obtain a crude powder (22.7mg) was redissolved in methanol (2 ml), and 80 // 1 was supplied to a HPLC column (DevelosilC30-UG-5, 2O0x) containing a 42.8% acetonitrile aqueous solution containing 10 mM ammonium formate. 150mm). The column was developed at a flow rate of 10.0ml / min, and the target substance was detected at 260nm UV light absorption. The holding time was 1.9 minutes, and the fraction was washed -63- 200414902 and divided into 25 times and collected. The obtained part with the same retention time was concentrated under reduced pressure and freeze-dried to obtain a crude powder El (13.3 mg) of Mramingin E1. (Example 3) Purification of Mramingin A will contain the above Mura Coarse powder A (2 5.1 mg) of menomycin A was dissolved in methanol (2 ml), and 80 / zl of the powder was supplied to an HPLC column (Develosil C3O-UG-5, equilibrated with a 42.8% acetonitrile aqueous solution containing 10 mM ammonium formate). 2O0x 150mm), the column was developed at a flow rate of 10.ml/min, and the target substance was detected by 260nm UV light absorption. The retention time of 22.4 minutes was collected in 25 times, and the part with the same retention time was subtracted. After concentrating under pressure, freeze-drying 'gave mramycin A (12.4 mg) as a colorless powder. (Example 4) Purification of mramycin B The crude powder B (29.9 mg) containing the above-mentioned mrammycin B was dissolved in methanol (2 ml), and 80 // 1 of the powder was supplied to a solution containing 10 mM ammonium formate. In an HPLC column (Develosil C30-UG-5, 20 0 X 1 50mm) equilibrated with a 42% acetonitrile aqueous solution, the column was developed at a flow rate of 10.Ornl / min. The target substance was detected by ultraviolet light absorption at 260 nm, and the retention time was 18.3 The fraction washed and separated in 25 minutes was collected in 25 times. The fraction obtained at the same retention time was concentrated under reduced pressure, and then freeze-dried to obtain a colorless powder of mramycin B (13.7 mg). (Example 5) Purification of mramycin C The crude powder B (42.5 mg) containing the above-mentioned mrammycin C was dissolved in methanol (3 ml), and 80 # 1 thereof was supplied to a solution containing 10 mM ammonium formate. In an HPLC column (Develosil C30-UG-5, 2000x 150mm) equilibrated with a 42.8% acetonitrile aqueous solution, the column was developed at a flow rate of 10.0 ml / min, and the target substance was detected by absorption of ultraviolet light at 260 nm. The retention time was 22.3 minutes. The portion was collected at 37 times-64-200414902. The obtained portion with the same holding time was concentrated under reduced pressure, and then freeze-dried to obtain a colorless powder of mramycin C (12.7 mg). (Constant Example 6) Purification of Mramingin D The crude powder D (11. 2 mg) containing the above-mentioned Mramingin D was dissolved in methanol (1 ml), and 80 // 1 of this was supplied to 1 OmM ammonium formate in a 42% acetonitrile aqueous solution equilibrated HPLC column (CAPCELLPAKC18UG12O, 2O0x 250mm), the column was developed at a flow rate of 100.0 μm 1 / minute, and the target substance was detected by absorption at 2 60 nm, and the retention time was 20.6 minutes. The portion was collected in 12 times, and the obtained portion with the same holding time was concentrated under reduced pressure, and then freeze-dried 'to obtain mramycin D (9.0 mg) as a colorless powder. (Example 7) Purification of Mlaminycin E 1 A coarse powder E 1 (1 3.3 mg) containing the above-mentioned mramycin E 1 was dissolved in methanol (1 ml), and 80 / z 1 of the powder was supplied to In an HPLC column (CAPCELL PAK C18UG120, 2θθ25〇111111) equilibrated with a 40% acetonitrile aqueous solution containing 10 mM ammonium formate, the column was developed at a flow rate of 10.1111 / min. The purpose of detection of ultraviolet light absorption of 26〇11111 Substance. The fraction with a holding time of 21.7 minutes was collected in 12 times. The obtained fraction with the same holding time was concentrated under reduced pressure, and then freeze-dried to obtain a colorless powder of mrammycin El (10.3 mg). (Example 8) Purification of mlaminomycin E2 The crude powder E2 (29.7 mg) containing the above-mentioned mrammycin E2 was dissolved in methanol (21111), and 80 // 1 of this was supplied to a mixture containing 1011 ^ 1 An HPLC column (DevelosilC30-UG-5,20 (/) X 150mm) equilibrated with 47.6% acetamidine in ammonium formate, the column was developed at a flow rate of 10.0ml / min, and the UV light absorption at 2 60nm was detected for the purpose Substance, holding time 18.3 minutes The fraction washed and washed was collected in 25 times -65- 200414902. The obtained same holding time was concentrated under reduced pressure and then 'freeze-dried' to obtain mrammycin E2 (19.0mg). Colorless powder. (Example 9) Purification of Mlaminin F 100 mg of the above-mentioned coarse powder F (445 mg) containing Mraminin F was dissolved in methanol (6 ml), and 80 // 1 of this was supplied to After passing through an HPLC column (Develosil C30-UG-5, 200x 150mm) equilibrated with a 40% acetonitrile aqueous solution containing 1 OmM ammonium bicarbonate, the column was developed at a flow rate of 1.0 ml / min. The target substance was retained for 2 1 · 1 minute, and the fraction washed and collected was divided into 7 5 times. The obtained fraction with the same retention time was 'reduced and concentrated under reduced pressure' and freeze-dried to obtain mramycin F (57.7 mg). Colorless powder. (Example 10) Obtaining and purification of mramycin Z1 and mramycin Z2 About the following purification, the active filtration was monitored by the following high-speed liquid chromatography (HPLC). Hamamycin Z1 column: CAPCELL PAKC18UG120 4.60X 150mm (manufactured by Shiseido Co., Ltd.) 10 mM ammonium bicarbonate aqueous solution with a flow rate of 1.0 m 1 / min. UV absorption was detected at 260 nm. Holding time: 9.2 minutes ( ii) Mlamycin Z2 CAPCELL PAKC18UG120 4.6 (/) X 150mm (made by Shiseido Co., Ltd.) Solvent: 3% acetonitrile aqueous solution containing 10 mM ammonium bicarbonate water 200414902 Flow rate: 1.0 m 1 / min Detection: UV Light absorption 2 600 nm Holding time: 1 3.0 minutes Column: CAPCELL PAK C18UG120 The mlamycin F (80 mg) obtained in Example 9 was dissolved in 50% methanol water containing 0.2N sodium hydroxide (10 ml) and stirred for 6 hours. After neutralizing with hydrochloric acid, it was concentrated under reduced pressure, and methanol was distilled off. This concentrated solution was washed twice with ethyl acetate (5m 1), and then freeze-dried. The obtained crude powder was dissolved in a 10 mM ammonium bicarbonate aqueous solution (2 ml), and 100 // 1 of this was supplied to a 10 mM ammonium bicarbonate-containing aqueous solution ^ itzFfj ^ HPLC1; ft (CAPCELLPAKC18UG12OJ 20 φχ 2 5 Omm). The precipitated solvent was washed at 23 minutes and developed in a column containing 10 mM ammonium bicarbonate in 5% acetonitrile aqueous solution at a flow rate of 10.ml/min. The target substance was detected at 260 nm ultraviolet light absorption. The retention time was washed at 16.0 minutes. Partial and 2 1.9-minute washing out of the portion will be collected in 20 times. The precipitated portions washed at the same retention time were combined and concentrated under reduced pressure, and then freeze-dried. The precipitated portions were washed at a retention time of 16 · 0 minutes to obtain mrammycin redundant 1 (11.8111§) as a colorless powder. The precipitate was washed at a time of 21.9 minutes to obtain mramycin Z2 (5.8 mg) as a colorless powder. (Test Example 1) Determination of antibacterial activity (anti-gram-positive bacterial activity) Mlamycin A, Mlamycin B, Mlamycin C, Mlamycin D, M Laminycin E1, Mlamycin E2, Mlamycin F, Mlamycin Z1, and Mlamycin Z 2 For Staphylococcus aureus FDA2 09P JC-1 strain (below The measurement of the minimum growth inhibitory concentration (MIC) for Staphylococcus aureus 2 09 P strain and Bacillus -67- 200414902 subtilis ATCC6633 strain (hereinafter referred to as "Bacillus subtilis 6633 strain") was performed by the following method. . The sample aqueous solution was diluted twice at a concentration of 1000 // g / ml to prepare 14 stages (1,000 # g / ml, 500 // g / ml, 250 // g / ml, 125 / zg / ml, 62.5 // g / ml, 31.3 // g / ml > 15.6 // g / mL · 7.8 // g / mL · 3.9 / ig / mL · 2 // g / mL · l // g / ml ^ 0.5 / g / ml, 0.24 // g / ml, 0.12 // g / ml) dilution. Each dilution was dispensed in 1 ml in a circular Petri disd (900x 20 mm, manufactured by Terumo), and then 9 ml of Muller-Intonagar agar medium (manufactured by BBL) was added and mixed to prepare a plate. The test bacteria Staphylococcus aureus 2 09 P and Bacillus subtilis 6 6 3 3 were cultured in trypsin casein glandular broth medium (T SB) medium (manufactured by Rongying Chemical Co., Ltd.) overnight and at 37 ° C. On the day of the test, the obtained bacterial solution was diluted 100-fold with TSB 'and smeared with two lines of plate culture medium with 1 platinum circle of bacteria. After the two-line smeared plate medium was cultured at 37 ° C for 18 hours, the MIC was determined. Test compound tested: Staphylococcus aureus Bacillus subtilis Mramingin A 25 25 Mramingin B 6.25 6.25 Mlamingin C 25 6.25 Mlamingin D 6.25 6.25 Mlamingin E 1 6.25 6.25 Mramingomycin E 2 6.25 6.25 Mramingmycin F 6.25 6.25 [Table 6] Antibacterial activity (anti-gram positive bacteria activity) _ MIC (β g / ml) -68- 200414902 From the above results, Shows lamycin A, lamycin B, lamycin C, lamycin D, lamycin E1, lamycin E2, and lamycin F It has antibacterial activity against Staphylococcus aureus 209 P strain and B. subtilis 66 3 3 strain. (Experimental Example 2) Measurement of Enzyme Inhibitory Activity of Translocation Enzyme I The enzyme inhibitory activity of each compound of the present invention on translocation enzyme I was determined by using an enzyme and UDP-N-ethylamyl-L-propylamine amidino-rD-glutamine Fluorenyl-m-diaminoheptafluorenyl- (Nε-dansalpinyl) -D-propylaminofluorenyl-D-alanine (110? -1 ^ -acetylixiurainyl-L-Ala-7-D-Glu-m -DAP- (N ε-dansyl) -D-Ala_ D-Ala) and phosphoric acid-unecaprenyl phosphate. That is, 'E. coli / pTA5 strain containing plastids encoding transposase I was cultured in Tris hydrochloric acid buffer solution (p Η 8 · 0) by ultrasonication, and then the crude extract was centrifuged. The obtained precipitate was dissolved with an interfacial active agent as an enzyme source to use 'UDP-N-ethylamido-L-propylaminoamido-rD-melamineamido-m-diaminoheptadienyl- ( Νε_Danthylpyridine-D-alanine and undecyl phosphate isoprene phosphate are incubated with the enzyme solution, and the fluorescence increased by the enzyme reaction is' excitation wavelength 3 5 5 nm, detection wavelength 5 The condition of 3 8 nm is quantified as the enzyme activity, and the 50% enzyme inhibitory concentration (IC5.) Is calculated from the concentration of the inhibitor added simultaneously. [Table 7] Translocation enzyme I inhibitory activity_ g formula IC 5 Q (// g / m 1) Mramycin A 0.0105 Mramycin B 0.0068 -69- 200414902 Mramycin c 0,, 0 104 Mramycin D 0, .00 9 9 Mramingin El 〇 (.0115 Mramingin E2 0, .0 109 Mramingin F 0, .00 8 9 Mramingin Z 1 0 • 03 13 Mlaminin Z2 0 .125 Mramingin A Mramingomycin B, Mlamingomycin C, Mlamingomycin D, Mlamingomycin E 1, Mlamingomycin E2, Mlamingomycin F, Mlamingomycin Z 1 and Mlaminomycin Z2 have inhibitory activity on translocation enzyme I. (Example 1 1) SANK6050 1 tetradecanoic acid addition culture (1) A SANK6050 strain grown on slant medium was cultured before Take a 1.5 cm corner hypha piece from a platinum ring, homogenize the hypha piece with a physiological saline solution, and put 80 ml of the culture medium before the composition described in Table 8 below into a 500 ml volume triangle flask (Seed flask) "sterile inoculation" Secondly, the flask was cultured in a Caudalie shaker at 28 ° C and 21 rpm for 6 days, and pre-cultured once. [Table 8] Pre-culture medium T-1 2 medium_glucose 3 () g Raw yeast lQg Soy flour 3 () g

CaC03 4§CaC03 4§

MgS04-7H20 2g -70- 200414902 消泡齊!ί (C B 4 4 2 ) 0 · 〇 5 g___ ※預先於100 °C煮沸30分鐘後使用 自來水 1000ml 滅菌前之pH値爲7·2 滅菌，121 °C滅菌分鐘。 (2)本培養 下列於表9及表1 〇中記載之2種類組成之滅菌結束後各自 將本培養培養基8 0 m 1放入5 0 0 m 1容量之燒瓶中種入（1)所得 到之前培養液5% ( V/V )植菌，以溫度28°C，210rpm培養12 曰。 本培養培養基 [表9]PCG-3培養基 _ 可溶性澱粉 7〇g Pharmamedia 3〇g C.S.L. 5g CaC03 4g MgS04.7H20 2g FeS0,7H20 ig 消泡劑（CB442) 0.05g 自來水 1000ml 滅菌前之pH値爲7.2， 滅菌，1 21 °C 3 0分鐘滅囷 0 [表10]PCG-4培養基 可溶性澱粉 7〇g 200414902MgS04-7H20 2g -70- 200414902 Antifoaming! Ί (CB 4 4 2) 0 · 〇5 g___ ※ Boil at 100 ° C for 30 minutes before using 1000ml tap water before sterilization. The pH 値 before sterilization is 7.2 sterilization, 121 ° C sterilize for minutes. (2) After the sterilization of the two types of compositions described in Tables 9 and 10 below, the culture mediums are each filled with 80 m 1 of this culture medium in a 500 m 1 flask and seeded in (1). The previous culture solution was 5% (V / V) planted bacteria, and cultured at a temperature of 28 ° C and 210 rpm for 12 days. This culture medium [Table 9] PCG-3 medium_ Soluble starch 70g Pharmamedia 30g CSL 5g CaC03 4g MgS04.7H20 2g FeS0,7H20 ig Defoamer (CB442) 0.05g Tap water 1000ml pH 値 before sterilization is 7.2 , Sterilized, sterilized at 1 21 ° C for 30 minutes [Table 10] Soluble starch of PCG-4 medium 70g 200414902

Pharmamedia 3 〇 g C . S . L . 5 gPharmamedia 30 g C. S. L. 5 g

CaC03 4gCaC03 4g

MgS04*7H20 2gMgS04 * 7H20 2g

FeS04*7H20 1 g 十四酸 5gFeS04 * 7H20 1 g myristic acid 5g

消泡劑（CB442)_〇.〇5g 自來水 1000ml 滅菌前之pH値爲7.2， 滅菌，121°C30分鐘滅菌。 於所得培養液3ml中加入乙腈6ml震盪10分鐘進行乙腌提 取，於離心分離（3000rpm，10分鐘）之上淸液中分離菌體， 此上淸液於 Automatic Environmental Speed V a c ( S e r v a n t 公^ 司製）中將乙腈f留出，注入SepPakPlusPS-2(Waters公司 製），以1 〇%乙腈水溶液3ml洗滌後，於50%乙腈水溶液3mi 中洗析出。此50%乙腈水溶液洗析液於Automatic Environmental Speed Vac中濃縮乾固。乾固物中加入二甲 亞楓0.3 m 1溶解，所得培養液換算1 〇倍濃縮樣本以下列高速 液體色層分析（HPLC)監測結果，示於第1圖，添加十四酸， 可增加姆拉明黴素F之生產量。 管柱： YMC-ODS-AM(S-3 //m) 12nm 2 5 0x 6mm I.D.(Wai.m.si) 溶劑： 含有〇 · 〇 5 %之三氟乙酸之5 3 %乙腈水溶液 流速： 1 . 0 m 1 /分鐘 200414902 檢出： 紫外光吸收260nm 保持時間： 45.1分鐘（姆拉明黴素F) (實施例12)SANK60501株之大容量培養 1) 一次培養 以白金圈取於斜面培養基上生長之SANK6 05 0 1株，將此 菌絲片於生理食鹽水均質化，將實施例1 1之表8記載之組成 之前培養培養基5 0 0ml加入7瓶2L之三角燒瓶（種燒瓶）中， 無菌接種，其次將該燒瓶於Caudalie震盪機中28°C、210rpm， 7曰間震盪培養，進行一次前培養。 2) 二次培養 該一次前培養液，將實施例1 1之表8中記載之組成之前培 養培養基滅菌終了後，30L放入60L容量槽培養機1基中以 5%(¥^)植菌，溫度28(：，通氣量1”111，槽內壓1〇〇1^&，回 轉數100至150rpm，溶解含氧量5ppm，2日間二次前培養。 3) 三次培養 將該二次前培養液，將實施例1 1之表8中記載之組成之前 培養培養基滅菌終了後，3 00L放入60L容量槽培養機1基中 以5%(V/V)植菌，溫度28C，通氣量lvvm，槽內壓l〇〇kPa， 回轉數8 5 r p m，2日間三次培養。 4) 本培養 將實施例1 1之表8中記載之組成之本培養培養基，4000L 放入60 00L容量槽培養機每1基之三次前培養液以7%(V/V)植 菌，溫度28C，通氣量lvvm，槽內壓l〇〇kPa，回轉數60至 120rpm，以溶解含氧量5ppm進行本培養，培養開始第5曰追 200414902 加滅菌水，第7日追加30%蔗糖液200L，培養1 1日間。 本培養培養基 [表 ll]PCG-5 改變培養基 可溶性澱粉 9〇g Pharmamedia 3〇g C.S.L. 5g CaC03 4g MgS04.7H20 2g FeS04*7H20 ig 十四酸 5g 反丁烯二酸 2,5g 消泡劑（CB442) 〇.2g 自來水 1000ml 滅菌前之pH値爲7.2， 滅菌，121〜125 X： 30分間滅菌。 (實施例13)姆拉明黴素G、姆拉明黴素Η、姆拉明黴素I之純 化 以下之純化中，活性濾分以下列高速液體色層分析（HP LC) 監測。 管柱： CAPCELL PAK C18UG120 4·6(/)χ 150mm(資生堂股份有限公司製） 溶劑： 含有〇·2%三基胺-磷酸緩衝液，以PH3.3調 節之5 5 %乙腈水溶液 流速： 1.0ml/分鐘 200414902 檢出； 紫外光吸收260nm 保持時間： 4.0分鐘（姆拉明黴素G) 6.5分鐘（姆拉明黴素H) 7·〇分鐘（姆拉明黴素I) 1)粗純化濾分之提取 實施例12所得培養終了液中加入水，以全量爲7 3 00 L稀 釋，此稀釋液添加矽藻土 5 45 ( 1 3 6.2kg)助過濾劑，以壓力過 濾器過濾，得到之菌體（681kg)中添加50%含水乙腈4200L 後，以壓力過濾器過濾。將所得之溶液及洗析液合倂 鲁 (46 6 0L)，pH以7 5 %硫酸（2· 6L)調整爲3後，以乙酸乙酯240 0L 進行2次提取，乙酸乙酯提取液（6 70 0L)以飽和食鹽水2000L 洗滌後，減壓濃縮至5 0 0L。所得濃縮液以磷酸緩衝液-水 (1 〇〇 L)調整pH至7,添加3回提取，接著將所得逆提取液（31 1L) 等分成2等分，送入以水平衡之Diaion HP20管柱（8L)中，管 柱以水（32L)及30%乙腈水溶液（32L)洗滌後，以90%乙腈水 溶液（4 0L)將活性物質洗析出，進行脫鹽。進行相同管柱色 層分析2次，將洗析液減壓濃縮得到油（3 3 7.6g)。 β 將此油溶於2L甲醇與乙腈1 : 1溶液中，取其中1L，供給 於以含有0.5%三乙基胺磷酸緩衝液調節pH爲3.4之40%乙腈 水溶液平衡之COSMOSIL管柱（36L)中，管柱以相同溶劑80L 洗滌後，以含0.5%三乙基胺磷酸緩衝液pH調節爲3.4之45% 乙腈水溶液（120L)，接著爲含0.5 %三乙基胺磷酸緩衝液pH 調節爲3.4之50%乙腈水溶液（120L)進行活性物質洗析，洗 析溶以每20L爲一部分，pH調節爲7之濾份4及5合倂，爲含 -75- 200414902 姆拉明黴素G之粗純化部份1 (4 0 L)，同樣地，濾份9中含姆 拉明黴素Η之粗純化部份2(2 0L)，及濾份10中含姆拉明黴素 1之粗純化部分3(20L)。 2)姆拉明黴素G之分離 上述粗純化部分1中取20 Oml減壓濃縮，得到之濃縮液 (100ml)供給於經水平衡之Diaion HP20管柱（10ml)中，以水 (50ml)洗滌管柱後’以90%乙腈水溶液（50ml)將活性物質洗 析進行脫鹽，所得洗析液經減壓濃縮後冷凍乾燥，得粗純 化粉末3 4 · 4 m g，將此粗純化粉末溶解於乙腈與甲醇1 : 1溶 液（2 m 1 )中，取其中1 5 0 // 1供給於經含〇 · 5 %三乙基胺磷酸緩 衝液調節p Η 3 · 3之4 8 · 4 %乙腈水溶液平衡之η P L C管柱 (CAPCELL PAK C18UG120，2〇0x 250mm)中，管柱以流速 9.0ml/分鐘展開，於260nm紫外光吸收檢出目的物質，保持 時間2 1 · 0分鐘洗析出之濾分分別取出，分別進行此操作1 3 次’將相同保持時間之部分合倂，調節p Η爲7後，經減壓濃 縮，供給於以水平衡之D i a i ο η Η Ρ 2 0管柱（1 〇 m 1)中，管柱以 水（50ml)洗滌後，以90%乙腈水溶液（50ml)將活性物質洗析 脫鹽。所得洗析液經減壓濃縮後冷凍乾燥，得到無色粉末 之姆拉明黴素G(17.8mg)。 (3)姆拉明黴素Η之分離 上述粗純化部分2中取60ml減壓濃縮，得到之濃縮液（3()nii) 供給於經水平衡之Sep pak Plus筒型管柱（iml)中，以水（5ml) 洗滌筒型管柱後，以90%乙腈水溶液（5ml)將活性物質洗析 進行脫鹽，所得洗析液經減壓濃縮後冷凍乾燥，得粗純化 -76- 200414902 粉末26.3mg，將此粗純化粉末溶解於乙腈與甲醇1 : 2溶液 (3ml)中，取其中2 5 0 // 1供給於經含0.5%三乙基胺磷酸緩衝 液調節？113.3之54.8%乙腈水溶液平衡之《^1^管柱 (CAPCELL PAK C18UG120，20 φ X 25 0mm)中，管柱以流速 9.0ml/分鐘展開，於260nm紫外光吸收檢出目的物質，保持 時間23.9分鐘洗析出之部分分別取出，分別進行此操作1 2 次，將相同保持時間之部分合倂，調節pH爲7後，經減壓濃 縮，供給於以水平衡之Sep pak Plus筒型管柱（5 ml)中，管柱 以水（5ml)洗滌後，以90%乙腈水溶液（5ml)將活性物質洗析 脫鹽。所得洗析液經減壓濃縮後冷凍乾燥，得到無色粉末 之姆拉明黴素H(14.0mg)。 (4)姆拉明黴素I之分離 上述粗純化部分3中取600ml減壓濃縮，得到之濃縮液 (300ml)供給於經水平衡之Diaion HP20管柱（l〇ml)中，以水 (5〇ml)洗滌管柱後，以90%乙腈水溶液（50ml)將活性物質洗 析進行脫鹽，所得洗析液經減壓濃縮後冷凍乾燥，得粗純 化粉末1 5 3 · 2mg，將此粗純化粉末溶解於乙腈與甲醇1 : 1溶 液（2ml)中，再以10mM重碳酸銨水（6ml) 3倍稀釋，取其 中200 μ 1供給於經水平衡之HPLC管柱（CAPCELL PAK C18UG120，20 0 X 2 5 0mm)中，管柱以流速9 · 0 ml /分鐘展開， 於26 0 nm紫外光吸收檢出目的物質，保持時間22.5分鐘洗析 出之部分分別取出，分別進行此操作40次，將相同保持時 間之部分合倂，經減壓濃縮，冷凍乾燥，得到含姆拉明黴 素I之醇化粉末7 · 7 m g，將此粗醇化粉末溶解於乙腈與甲醇 -77- 200414902 1 : 1溶液（6 0 0 // 1)中，再以調節ρ Η爲3 . 3之0.5 %三乙基胺磷 酸水（6 0 0 // 1)作2倍稀釋，取其中1 5 0 // 1供給於經含〇 . 5 %三乙 基胺磷酸緩衝液調節pH3.3之54%乙腈水溶液平衡之HPLC管 柱（CAPCELL PAK C18UG120，20 0 X 25 0mm)中，管柱以流 速9.Oml/分鐘展開，於260nm紫外光吸收檢出目的物質，分 別取出保持時間22.2分鐘洗析之部分，分別進行此操作8 次，所得相同保持時間之部分合倂，調節p Η爲7後，減壓濃 縮，供給於經水平衡之Sep pak Plus PS-2筒型（lml)中，筒 型以水（5ml)洗滌後，以90%乙腈水溶液（5ml)溶出活性物質 脫鹽，所得溶出液經減壓濃縮後，冷凍乾燥，得到無色粉 末之姆拉明黴素I(1.9mg)。 (實施例14) SANK6 605 0 1株之十三酸添加培養 (1 )前培養 在斜面培養基上生長之SANK60 5 0 1株，以白金圈取之 1.5 cm角落之菌絲片，將此菌絲片於生理食鹽水均質化之均 質物，將實施例1 1之表8中記載之組成之前培養培養基8 Oml 放入5 0 0 m 1容量之1個三角燒瓶（種燒瓶）中，無菌接種’ 其次將該燒瓶於Caudalie震盪機中，28°C，210rpm震盪培養 6曰，進行一次前培養。 (2)本培養 將實施例1 1之表9記載之組成之本培養培養基滅菌結束 後，或於此1 L中加入〇 . 5 %十三酸之培養基（表1 2 ) ’各自 將8 0 m 1前培養液放入5 0 0 m 1容量之燒瓶中，以5 % ( V / V )植 菌，以溫度28°C，210rpm培養12日。 200414902 本培養培養基 [表12]PCG-3T培養基 可溶性澱粉 70g Pharmamedia 3〇g C.S.L. 5g CaC03 4g MgS04*7H20 2g FeS04.7H20 1 g 十三酸 5g 消泡劑（CB442) 0.05g 自來水 1 000ml 滅菌前之pH値爲7.2， 滅菌，1 2 1°C 3 0分鐘滅菌。 依據實施例1 1之方法調製HP LC樣品，活性部分以下列高 速液體色層分析（HP LC)監測之結果示於第2圖中，十三 酸之添加會增加姆拉明黴素B之生產量。 管柱： YMC-ODS-AM(S-3//m) 12nm 2 5 0x 6mm I. D . (W a i. m . s i) 溶劑： 含有0.0 5 %之三氟乙酸之5 3 %乙腈水溶液 流速： 1 · 0 m 1 /分鐘 檢出： 紫外光吸收260nm 保持時間： 28.5分鐘（姆拉明黴素F) (試驗例3)姆拉明黴素G、Η、I之轉位酵素〗酵素抑制活性之 測定 -79- 200414902 本發明之各化合物對於轉位酵素i之酵素抑制活性，使用 酵素與UDP-N -乙醒基-L-丙胺醯基- 魅胺醯基·πι-二胺基 庚一Μ基- (Νε-丹薩）-D -丙胺薩基-D-丙胺酸（110?-：^-acetylmuramyl-L-Ala - γ - D-Glu-m-DAP-(Ne-dansyl)-D-Ala-D-Ala)及磷酸十一院異戊二嫌酯（undecaprejlyiph〇Sphate)之 反應來測定。 即’將含編碼轉位酵素I之質體之大腸菌E · c ο 1 i / p T A 5株培 養所得菌體於Tris鹽酸緩衝液（pH8.0)中以超音波震碎後， 將粗提取液離心，得到之沉澱以界面活性劑溶化之溶液作 爲酵素源來使用，UDP-N-乙醯基-L-丙胺醯基-T-D-麩胺醯 基-I二胺基庚二醯基-(N\丹醯）-D-丙胺醯基-D-丙胺酸及 磷酸十一烷異戊二烯酯與酵素液培育後，酵素反應所增加 之螢光度，以激發波長3 5 5 nm，檢出波長5 3 8nm之條件定量 爲酵素活性’ 50%酵素抑制濃度（IC5Q)由同時添加抑制劑之 濃度與自抑制率計算而求出。其結果示於表i 3。 [表13]轉位酵素I抑制活性 試驗化合物 IC50( β g/ml) • 姆拉明黴素G 0.0134 姆拉明黴素Η 0.0186 姆拉明黴素I 0.0094 顯示出姆拉明黴素G、姆拉明黴素Η及姆拉明黴素I對轉位 酵素I有抑制活性。 (實施例15)姆拉明黴素Ζ3及姆拉明黴素ζ 4之取得及純化 二乂 Τ列方法，將姆拉明黴素I作爲起始材料可取得姆拉明 -80- 200414902 黴素Z3及姆拉明黴素Z4。 以實施例13所得姆拉明黴素I溶解於含〇.2N氫氧化鈉之 5 〇%甲醇水中，攪拌6小時之溶液以鹽酸中和後，減壓濃縮 餾去甲醇，此濃縮液以乙酸乙酯洗滌2次後冷凍乾燥，將所 得粗粉末溶解於10mM重碳酸銨水溶液中，將此溶液供給於 經含10mM重碳酸銨水平衡之HPLC管柱（CAPCELL PAK C18UG120，20 0 X 250mm) ^洗析溶劑於23分鐘含有10 mM重 碳酸銨之5%乙腈水溶液之梯度，管柱於流速10.Oml/分鐘展 開，於260nm紫外光吸收檢出目的物質，保持時間所溶出之 部分分數回分別收取，將相同保持時間所溶出之部分合倂， 各別經減壓濃縮後冷凍乾燥，可得到姆拉明黴素Z3或姆拉 明黴素Z4之粉末。關於保持時間之決定，基於HPLC圖表可 由業者選擇。 (製劑例）膠囊劑 姆拉明黴素F 1000 mg 乳糖 1 00η ig 玉米澱粉 148. 8mg 硬脂酸鎂 1.2m g 全量 3 5 0η ig 混合上述處方之粉末，通過60網眼之篩子後，將此粉末 裝入膠囊中。 【圖式簡單說明】 第1圖 實施例1 1所得部分之Η P L C圖表（1 - A :未添加十四 酸、：UB :添加十四酸）。箭號表示姆拉明黴素ρ之高峰。 •81- 200414902 第2圖 實施例14所得部分之HPLC圖表（2-A :未添加十三 酸、2-B :添加十三酸）。箭號表示姆拉明黴素B之高峰。Defoamer (CB442) _. 05g tap water 1000ml pH 前 before sterilization is 7.2, sterilize, sterilize at 121 ° C for 30 minutes. Add 3 ml of acetonitrile to 3 ml of the obtained culture solution and shake for 10 minutes to perform acetic pickle extraction. Isolate the bacterial cells in the centrifugal separation (3000 rpm, 10 minutes). The supernatant is separated in Automatic Environmental Speed V ac (Servant) The acetonitrile f was left out in the company), injected into SepPakPlusPS-2 (manufactured by Waters), washed with 3 ml of a 10% acetonitrile aqueous solution, and washed and precipitated in 3 mi of a 50% acetonitrile aqueous solution. This 50% acetonitrile aqueous solution was concentrated and dried in Automatic Environmental Speed Vac. Dried methylene maple 0.3 m 1 was added to dissolve, and the obtained culture solution was converted into a 10-fold concentrated sample. The following high-speed liquid chromatography (HPLC) monitoring results are shown in Figure 1. Adding tetradecanoic acid can increase Production of lamycin F. Column: YMC-ODS-AM (S-3 // m) 12nm 2 50x 6mm ID (Wai.m.si) Solvent: 5% acetonitrile aqueous solution containing 0.05% trifluoroacetic acid Flow rate: 1 0 m 1 / min 200414902 Detection: UV light absorption at 260 nm Hold time: 45.1 minutes (Mramingin F) (Example 12) Large-capacity culture of SANK60501 strain 1) Primary culture was taken on a slanted medium with platinum rings A growing strain of SANK6 05 0, this mycelium piece was homogenized in physiological saline, and 500 ml of the culture medium before the composition described in Table 8 of Example 11 was added to 7 2L Erlenmeyer flasks (seed flasks). Sterile inoculation, followed by incubating the flask in a Caudalie shaker at 28 ° C, 210 rpm, and shaking for 7 days. 2) The secondary preculture solution was cultured. After the sterilization of the culture medium before the composition described in Table 8 of Example 11 was completed, 30L was placed in a base of a 60L capacity tank incubator and 5% (¥ ^) was used to plant the bacteria. , Temperature 28 (:, aeration volume 1 "111, tank pressure 1001 ^ &, number of revolutions 100 to 150 rpm, dissolved oxygen content of 5 ppm, two days before the second incubation. 3) three cultures this second For the pre-culture medium, after sterilizing the culture medium before the composition described in Table 8 of Example 11, 300L was placed in a base of a 60L capacity tank incubator at 5% (V / V), and the temperature was 28C. The amount of lvvm, the pressure in the tank was 100 kPa, the number of revolutions was 85 rpm, and the culture was performed three times in 2 days. 4) In this culture, 4000 L of the culture medium of the composition described in Table 8 of Example 11 was placed in a 60 00 L capacity tank. The culture medium was planted with 7% (V / V) of the culture medium every three times before the culture, the temperature was 28C, the ventilation volume was lvvm, the pressure in the tank was 100 kPa, the number of revolutions was 60 to 120 rpm, and the dissolved oxygen content was 5 ppm. Cultivation, the 5th day after the start of cultivation, 200414902, adding sterilized water, and adding 200L of 30% sucrose solution on the 7th day, and culturing for 11 days. The culture medium [Table 11] PCG-5 changes Media soluble starch 90g Pharmamedia 30g CSL 5g CaC03 4g MgS04.7H20 2g FeS04 * 7H20 ig Tetradecanoic acid 5g Fumaric acid 2,5g Defoamer (CB442) 0.2g Tap water 1000ml pH before sterilization 値It is 7.2, sterilized, 121 ~ 125 X: sterilized in 30 minutes. (Example 13) Purification of mlamycin G, mlamycin Η, and mlamycin I In the purification below, the active fraction is less than High-speed liquid chromatography (HP LC) monitoring. Column: CAPCELL PAK C18UG120 4 · 6 (/) χ 150mm (made by Shiseido Co., Ltd.) Solvent: Contains 0.2% triylamine-phosphate buffer solution at pH 3 .3 Adjusted flow rate of 55% acetonitrile aqueous solution: 1.0ml / min 200414902 Detection; UV light absorption at 260nm Hold time: 4.0 minutes (mramingomycin G) 6.5 minutes (mramingomycin H) 7.0 minutes (Mramingomycin I) 1) Extraction of the crude purification filter 12 The final culture solution obtained in Example 12 was added with water and diluted with a total amount of 7 3 00 L. This dilution was added with diatomaceous earth 5 45 (1 3 6.2 kg ) Filter aid, filtered with a pressure filter, 50% water-containing B was added to the obtained bacteria (681kg) After 4200L, it was filtered with a pressure filter. The obtained solution and eluate were combined with Hirudo (46 6 0L), and the pH was adjusted to 3 with 75% sulfuric acid (2.6L), and then carried out with 240 0L of ethyl acetate. After extraction, the ethyl acetate extract (6 70 0L) was washed with 2000L of saturated brine, and then concentrated to 500L under reduced pressure. The obtained concentrated solution was adjusted to pH 7 with phosphate buffered water (100 L), and added 3 times for extraction. Then the obtained reverse extract (31 1 L) was divided into 2 equal parts and sent to a Diaion HP20 tube equilibrated with water. In the column (8L), the column was washed with water (32L) and a 30% acetonitrile aqueous solution (32L), and then the active material was washed out and precipitated with a 90% acetonitrile aqueous solution (40L), and desalted. The same column chromatography was performed twice, and the eluate was concentrated under reduced pressure to obtain an oil (3 3 7.6 g). β This oil was dissolved in 2L methanol and acetonitrile 1: 1 solution, 1L was taken out, and it was supplied to a COSMOSIL column (36L) equilibrated with a 40% acetonitrile aqueous solution adjusted to pH 3.4 with 0.5% triethylamine phosphate buffer solution. In the column, the column was washed with 80 L of the same solvent, and then the pH was adjusted to 45% acetonitrile aqueous solution (120 L) containing 0.5% triethylamine phosphate buffer solution, and the pH was adjusted to 0.5% triethylamine phosphate buffer solution. The 50% acetonitrile aqueous solution (120L) in 3.4 was used for elution of the active substance. The elution was carried out at a fraction of 20L and the pH was adjusted to 7 with 4 and 5 mashes, which contained -75- 200414902 Crude purified fraction 1 (40 L). Similarly, crude fraction 2 (20 L) containing mlaminomycin Η in filter 9 and crude fraction mlamycin 1 in filter 10 Purified part 3 (20L). 2) Isolation of Mramminycin G From the above crude purification part 1, 20 Oml was concentrated under reduced pressure. The obtained concentrate (100ml) was supplied to a water-equipped Diaion HP20 column (10ml), and water (50ml) was used. After washing the column, the active material was desalted with a 90% acetonitrile aqueous solution (50 ml) and desalted. The obtained eluate was concentrated under reduced pressure and freeze-dried to obtain a crude purified powder 3 4 · 4 mg. This crude purified powder was dissolved in In a 1: 1 solution of acetonitrile and methanol (2 m 1), take 1 50 0 // 1 and adjust it with 0.5% triethylamine phosphate buffer solution p Η 3 · 3 of 4 8 · 4% acetonitrile In an η PLC column (CAPCELL PAK C18UG120, 200x 250mm) equilibrated with an aqueous solution, the column was developed at a flow rate of 9.0 ml / min, and the target substance was detected at 260 nm ultraviolet light absorption. The retention time was 2 1 · 0 minutes and the precipitated filter was washed. Take out each of them separately, and perform this operation 13 times respectively. 'Combine the parts with the same holding time, adjust p Η to 7, and then concentrate under reduced pressure, and supply to the Diai ο η Η P 2 0 column with water balance ( In 10m 1), the column was washed with water (50ml), and the active substance was washed out with 90% acetonitrile aqueous solution (50ml). Desalination. The obtained eluate was concentrated under reduced pressure and then freeze-dried to obtain mlamycin G (17.8 mg) as a colorless powder. (3) Isolation of mramycin IX: 60 ml of the above crude purification part 2 was concentrated under reduced pressure, and the obtained concentrated solution (3 () nii) was supplied to a Sep pak Plus cartridge column (iml) equilibrated with water. After the cylindrical column was washed with water (5 ml), the active substance was washed out and desalted with a 90% acetonitrile aqueous solution (5 ml). The obtained eluate was concentrated under reduced pressure and freeze-dried to obtain crude purified -76- 200414902 powder 26.3 mg, dissolve this crude purified powder in acetonitrile and methanol 1: 2 solution (3ml), and take 2 5 0 // 1 to adjust it with 0.5% triethylamine phosphate buffer solution? In 113.3 column with a 54.8% acetonitrile aqueous solution, a column (CAPCELL PAK C18UG120, 20 φ X 25 0mm) was developed at a flow rate of 9.0 ml / min. The target substance was detected at 260 nm UV light absorption, and the retention time was 23.9 The fractions separated by washing in minutes were taken out separately, and this operation was performed 12 times. The parts with the same holding time were combined. After adjusting the pH to 7, it was concentrated under reduced pressure and supplied to a Sep pak Plus cartridge column balanced with water ( 5 ml), the column was washed with water (5 ml), and the active material was washed out and desalted with a 90% acetonitrile aqueous solution (5 ml). The obtained eluate was concentrated under reduced pressure and then freeze-dried to obtain mramycin H (14.0 mg) as a colorless powder. (4) Isolation of Mramminycin I 600 ml of the crude purification part 3 was concentrated under reduced pressure, and the obtained concentrate (300 ml) was supplied to a water-equipped Diaion HP20 column (10 ml), and water ( (50 ml) After washing the column, the active substance was washed out with 90% acetonitrile aqueous solution (50 ml) for desalting. The obtained eluate was concentrated under reduced pressure, and then freeze-dried to obtain a crude purified powder 153. 2 mg. The purified powder was dissolved in a 1: 1 solution of acetonitrile and methanol (2 ml), and then diluted three times with 10 mM ammonium bicarbonate water (6 ml). 200 μ 1 of the purified powder was supplied to a water-balanced HPLC column (CAPCELL PAK C18UG120, 20 0 X 2 50 mm), the column was developed at a flow rate of 9 · 0 ml / min, the target substance was detected at 2600 nm UV light absorption, and the separated part was washed out for a holding time of 22.5 minutes, and this operation was performed 40 times respectively. The parts with the same holding time were combined, concentrated under reduced pressure, and freeze-dried to obtain an alcoholized powder containing 7 · 7 mg of mrammycin I. This crude alcoholized powder was dissolved in acetonitrile and methanol-77- 200414902 1: 1 0.5% triethylamine phosphoric acid in solution (6 0 0 // 1) to adjust ρ Η to 3.3 Water (6 0 0 // 1) was diluted twice, and 1 50 0 // 1 was taken and supplied to an HPLC tube equilibrated with a 54% acetonitrile aqueous solution adjusted to pH 3.3 with 0.5% triethylamine phosphate buffer solution. In the column (CAPCELL PAK C18UG120, 20 0 X 25 0mm), the column was developed at a flow rate of 9.Oml / min, and the target substance was detected at 260nm ultraviolet light absorption. The fractions with a retention time of 22.2 minutes were taken out, and this operation was performed separately. Eight times, the obtained parts with the same holding time were combined. After adjusting p Η to 7, it was concentrated under reduced pressure and supplied to a water-balanced Sep pak Plus PS-2 cartridge (1ml). The cartridge was washed with water (5ml). Then, the active material was desalted with a 90% acetonitrile aqueous solution (5 ml), and the obtained eluate was concentrated under reduced pressure, and then freeze-dried to obtain mrammycin I (1.9 mg) as a colorless powder. (Example 14) SANK6 605 0 strain of tridecanoic acid was added (1) Before cultivation, SANK60 501 strain grown on slant medium was cultured, and a 1.5 cm corner hypha piece was taken from a platinum circle, and this hypha was obtained. The tablet was homogenized with a physiological saline solution, and the culture medium 8 ml before the composition described in Table 8 of Example 11 was put into a 500 m 1 flask with a capacity of 1 ml, which was inoculated aseptically. Next, the flask was cultured in a Caudalie shaker at 28 ° C and 210 rpm for 6 days, and a preculture was performed. (2) In the present culture, after sterilization of the present culture medium having the composition described in Table 9 of Example 11 was completed, or 0.5% tridecanoic acid medium (Table 1 2) was added to this 1 L. The culture medium before m 1 was put into a 500 m 1 capacity flask, and the bacteria were planted at 5% (V / V), and cultured at a temperature of 28 ° C and 210 rpm for 12 days. 200414902 This culture medium [Table 12] PCG-3T medium soluble starch 70g Pharmamedia 30g CSL 5g CaC03 4g MgS04 * 7H20 2g FeS04.7H20 1 g tridecanoic acid 5g defoamer (CB442) 0.05g tap water 1 000ml before sterilization Sterilize at pH 7.2, sterilize at 121 ° C for 30 minutes. The HP LC sample was prepared according to the method of Example 11. The active part was monitored by the following high-speed liquid chromatography (HP LC). The results are shown in Figure 2. The addition of tridecanoic acid will increase the production of mrammycin B. the amount. Column: YMC-ODS-AM (S-3 // m) 12nm 2 50x 6mm I. D. (W a.m. si) Solvent: 5 3% acetonitrile aqueous solution containing 0.05% trifluoroacetic acid Flow rate: 1 · 0 m 1 / min Detection: UV light absorption at 260nm Holding time: 28.5 minutes (Mramingin F) (Test Example 3) Translocation enzymes of Mramingin G, Gadolinium, and I〗 Enzymes Measurement of inhibitory activity-79- 200414902 The enzyme inhibitory activity of each compound of the present invention on translocation enzyme i, using an enzyme and UDP-N -ethoxyl-L-propylaminofluorenyl-melamine amino · π-diamine Heptamyl- (Nε-Dansa) -D-Arysalamine-D-Alanine (110?-: ^-Acetylmuramyl-L-Ala-γ-D-Glu-m-DAP- (Ne-dansyl) -D-Ala-D-Ala) and undecaprejlyiph Sphate. That is, 'E. c. 1 i / p TA containing 5 plastids encoding the transposase I was cultured in Tris hydrochloric acid buffer (pH 8.0) by ultrasonication, and the crude extract was then extracted. Liquid centrifugation, the resulting precipitate was dissolved with a surfactant-dissolved solution as an enzyme source, UDP-N-ethylamyl-L-propylaminofluorenyl-TD-glutamine-imidyl-I diaminoheptamidyl- ( N \ Danyl) -D-Alanine-D-Alanine and Undecane Phosphate Isoprenyl Phosphate after incubation with the enzyme solution, the fluorescence increased by the enzyme reaction, with an excitation wavelength of 3 5 5 nm, detected The condition of the wavelength of 5 3 8nm is quantified as the enzyme activity '50% enzyme inhibition concentration (IC5Q), which is calculated from the concentration of the inhibitor and the self-inhibition rate. The results are shown in Table i 3. [Table 13] Translocation enzyme I inhibitory activity test compound IC50 (β g / ml) • Mramingomycin G 0.0134 Mramingomycin Η 0.0186 Mramingomycin I 0.004 Mlamycin Η and Mlamycin I have inhibitory activity on translocation enzyme I. (Example 15) A method for obtaining and purifying mramingomycin Z3 and mramingomycin ζ 4, and using mramingin I as a starting material, Mraming-80-200414902 Z3 and Mlaminomycin Z4. The mrammycin I obtained in Example 13 was dissolved in 50% methanol water containing 0.2N sodium hydroxide, and the solution was stirred for 6 hours to neutralize with hydrochloric acid. Then, the methanol was concentrated by distillation under reduced pressure, and the concentrated solution was acetic acid. The ethyl acetate was washed twice and then freeze-dried. The obtained crude powder was dissolved in a 10 mM ammonium bicarbonate aqueous solution, and this solution was supplied to an HPLC column (CAPCELL PAK C18UG120, 20 0 250 mm) equilibrated with water containing 10 mM ammonium bicarbonate. ^ The elution solvent contained a gradient of 10 mM ammonium bicarbonate in 5% acetonitrile aqueous solution at 23 minutes, and the column was developed at a flow rate of 10.ml/min. The target substance was detected at 260 nm ultraviolet light absorption, and the fractions dissolved during the retention time were returned to separate Take it, combine the part eluted at the same holding time, and freeze-dry it after concentrating under reduced pressure, respectively, to obtain the powder of mlamycin Z3 or M4. The determination of the retention time can be selected by the operator based on the HPLC chart. (Formulation example) Capsule Mramminycin F 1000 mg Lactose 1 00η ig Corn starch 148.8 mg Magnesium stearate 1.2mg Whole amount 3 5 0η ig Mix the powder of the above prescription and pass through a 60-mesh sieve. The powder is filled into capsules. [Brief description of the figure] Fig. 1 Illustrated in Example 1 of the obtained part 1 P L C chart (1-A: no tetradecanoic acid added, UB: added tetradecanoic acid). The arrow indicates the peak of mlaminomycin p. • 81- 200414902 Figure 2 HPLC chart of the part obtained in Example 14 (2-A: tridecanoic acid was not added, 2-B: tridecanoic acid was added). The arrow indicates the peak of mrammycin B.

-82--82-

Claims (1)

200414902 拾、申請專利範圍： 1.〜種下列一般式⑴ 、J所不之化合物或其鹽200414902 Scope of patent application: 1. ~ The following compounds of general formula ⑴, J or their salts (I) [式中，R爲烴鏈]。 2·如申請專利範圍第i項之化合物或其鹽，其中11爲飽和烴 鏈。 3. 如申請專利範圍第2項之化合物或其鹽，其中直鏈狀 飽和烴鏈。 4. 如申請專利範圍第3項之化合物或其鹽，其中R爲碳數7至 1 7之直鏈狀飽和烴鏈。 5 ·如申g靑專利範圍第4項之化合物或其鹽，其中R爲碳數9至 1 5之直鏈狀飽和烴鏈。 6. 如申請專利範圍第5項之化合物或其鹽，其中r表示_ (CH2)9CH3 或-(CH2)10CH3。 7. 如申請專利範圍第2項之化合物或其鹽，其中r表示_ (CH2)8CH(CH3)2 〇 8 ·如申請專利範圍第1項之化合物或其鹽，其中r爲直鏈狀 不飽和烴鏈。 -83- 200414902 9 ·如申請專利範圍桌8項之化合物或其鹽，宜中&表示 (CH2)3CH = CH(CH2)5CH3、 -CH2CH = CH(CH2)7CH3、 - (CH2)3CH = CHCH2CH = CH(CH2)4CH3 > (CH2)3CH = CH(CH2)6CH3。 1 0 . —種下列一般式（π )所不之化合物或其鹽，(I) [wherein R is a hydrocarbon chain]. 2. A compound or a salt thereof according to item i of the patent application, wherein 11 is a saturated hydrocarbon chain. 3. A compound or a salt thereof according to item 2 of the scope of patent application, wherein the saturated hydrocarbon chain is linear. 4. The compound or a salt thereof according to item 3 of the scope of patent application, wherein R is a linear saturated hydrocarbon chain having 7 to 17 carbon atoms. 5. The compound or salt thereof as claimed in item 4 of the patent application, wherein R is a linear saturated hydrocarbon chain having 9 to 15 carbon atoms. 6. The compound or its salt as claimed in item 5 of the patent application, wherein r represents _ (CH2) 9CH3 or-(CH2) 10CH3. 7. If the compound or a salt thereof in the second item of the scope of the patent application, where r represents _ (CH2) 8CH (CH3) 2 0 8 · If the compound or the salt of the first scope of the patent application, in which r is a linear Saturated hydrocarbon chain. -83- 200414902 9 · If the compound of Table 8 of the scope of patent application or its salt is suitable, & means (CH2) 3CH = CH (CH2) 5CH3, -CH2CH = CH (CH2) 7CH3,-(CH2) 3CH = CHCH2CH = CH (CH2) 4CH3 > (CH2) 3CH = CH (CH2) 6CH3. 1 0. —A compound or a salt thereof not represented by the following general formula (π), [式中，R爲烴鏈]。 1 1 ·如申請專利範圍第1 0項之化合物或其鹽，其中R爲直鏈 狀飽和烴鏈。 1 2 .如申g靑專利範圍桌1 1項之化合物或其鹽，其中R爲碳數7 至1 7之直鏈狀飽和烴鏈。 1 3 ·如申|靑專利範圍桌1 2項之化合物或其鹽，其中r爲碳數9 至1 5之直鏈狀飽和烴鏈。 1 4 ·如申S靑專利範圍桌1 3項之化合物或其鹽，其中R表示 (ch2)i〇ch3。 I5· —種下列一般式（m)所示之化合物或其鹽， -84- 200414902[Wherein R is a hydrocarbon chain]. 1 1 · The compound or a salt thereof according to item 10 of the scope of patent application, wherein R is a linear saturated hydrocarbon chain. 12. A compound or a salt thereof as described in Table 11 of Table 11 of the Patent Scope, wherein R is a linear saturated hydrocarbon chain having 7 to 17 carbon atoms. 1 3. The compound or salt thereof as described in Table 12 of the scope of the patent application of R & S, where r is a linear saturated hydrocarbon chain having 9 to 15 carbons. 14. The compound or a salt thereof as set forth in Table 13 of the scope of patent application, wherein R represents (ch2) ioch3. I5 · —a compound represented by the following general formula (m) or a salt thereof, -84- 200414902 [式中，R爲烴鏈]。 1 6 .如申請專利範圍第1 5項之化合物或其鹽，其中R爲直鏈 狀飽和烴鏈。 17. 如申請專利範圍第16項之化合物或其鹽，其中R爲碳數7 至1 7之直鏈狀飽和烴鏈。 18. 如申請專利範圍第17項之化合物或其鹽，其中R爲碳數9 至1 5之直鏈狀飽和烴鏈。 1 9 .如申請專利範圍第1 8項之化合物或其鹽，其中11表示-(CH2)10CH3。 20.—種下列一般式（IV)所示之化合物或其鹽，[Wherein R is a hydrocarbon chain]. 16. The compound or a salt thereof according to item 15 of the scope of patent application, wherein R is a linear saturated hydrocarbon chain. 17. The compound or a salt thereof according to item 16 of the application, wherein R is a linear saturated hydrocarbon chain having 7 to 17 carbon atoms. 18. A compound or a salt thereof as claimed in claim 17 in which R is a linear saturated hydrocarbon chain having 9 to 15 carbon atoms. 19. The compound or a salt thereof according to item 18 of the scope of patent application, wherein 11 represents-(CH2) 10CH3. 20. a compound represented by the following general formula (IV) or a salt thereof, -85- 200414902 [式中，R爲烴鏈]。 2 1 ·如申S靑專利範圍第2 〇項之化合物或其鹽，其中r爲直鏈 狀飽和經鏈。 21·如申請專利範圍第11項之化合物或其鹽，其中r爲碳數7 至1 7之直鏈狀飽和烴鏈。 23·如申請專利範圍第22項之化合物或其鹽，其中r爲碳數9 至1 5之直鏈狀飽和烴鏈。 24·如申請專利範圍第23項之化合物或其鹽，其中r表示_ (ch2)10ch3。 25.—種下列一般式（V)所不之化合物或宜臨，-85- 200414902 [wherein R is a hydrocarbon chain]. 2 1 A compound or a salt thereof as claimed in item 20 of the patent application, wherein r is a linear saturated warp chain. 21. The compound or a salt thereof according to item 11 of the scope of application, wherein r is a linear saturated hydrocarbon chain having 7 to 17 carbon atoms. 23. A compound or a salt thereof according to item 22 of the scope of application, wherein r is a linear saturated hydrocarbon chain having 9 to 15 carbon atoms. 24. The compound or its salt according to item 23 of the scope of patent application, wherein r represents _ (ch2) 10ch3. 25.—A compound not suitable for the following general formula (V) or advisable, (V)(V) 〇 26·—種下列一般式（VI)所示之化合物或其鹽〇 26 · —A compound represented by the following general formula (VI) or a salt thereof (VI) -86- 1 7·—種下列一般式（VII)所示之化合物或其鹽， 200414902(VI) -86- 1 7 · —A compound represented by the following general formula (VII) or a salt thereof, 200414902 (V I I ) o 28.—種下列一般式（VIII)所示之化合物或其鹽，(V I I) o 28. a compound represented by the following general formula (VIII) or a salt thereof, (VIII) 〇 2 9.—種具有下列物理化學性狀之化合物或其鹽， 1 )物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞碾，不溶於氯仿 3) 分子式：C55H85N5 02 3 4) 分子量：1183(以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[M + H] +如下 列表示： 實測値：1 1 8 4.5 6 9 9 計算値：1 1 8 4.5 7 1 3 6) 紫外線吸收光譜： -87- 200414902 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表 示： 263nm(e9200) 7) 旋光度： 於甲醇中測定旋光度，如下列所示値表示： [a ]D29 : +7.5 ° ( c0.5 ) 8) 紅外線吸收光譜： 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下 列所示之極大吸收表示： 3414，2928,2856,1738,1696,163 1，1465,1 384,1273, il6l 1 1 27,1 1 04,1 0 1 5,9 60cm·1 9) iH-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞碾（2.49ppm } 測定，以下所示爲其1 H-核磁共振光譜： 0.84(6H，t)，0.9 1(3H，d，J = 6.2Hz)，1.2-1.3(10H，m)，1.42(lH，m)，1.57(2H，m),1.7 1(lH，m)，2.0(7 H5m)，2.12(lH，m)，2.16(lH，m)，2.26(3H,s)，2.3(3H5m)2 4 1(lH，m)，2.46(2H5m)52.6(4H，m)，2.80(lH，dd，J = 6.6，l2 8Hz)，2.92(3H，s)，2.94(lH，m)，2.98(lH，bi*.m)，3.26(lH t J = 9.2Hz),3.36(3H5s),3.37(3H?s)?3.4(2H?m)?3.53(iH m )，3.83(lH，d，J = 8.4Hz)53.9(3H，m)，4.13(lH，m)，4.l9(2H m)，4.96(1 H，dd，J = 2.9,9.2Hz)，5· 12(lH，m)，5.3(2H，m)5 37(2H，m)，5.65(lH，d，J = 7.7Hz)，5.90(lH，t，J = 5.9HZ)，5 9 3(lH，m)，7.82(lH，d，J = 7.7)ppm -88- 200414902 10) 13C-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞楓（39.5ppm) 測定，以下所示爲其13C -核磁共振光譜： 9.5(q)，14.0(q)，19.0(q)，22.1(t)，23.9(t)，24.8(t)，26.3(t)， 26.6(t)，27. 1 (d)，28.3(t)，28.7(t)，29. 1 (t)，9.2(t),3 1 ·2(〇, 32.9(t)，3 6.4(q)，3 7.8(q)，3 8.8(t)，9.8(t)，3 9.9(t)，40.2(t)， 40.6(t)，41.5(t)，56.6(t)，8.7( q)，60.0( q)，62.3(d)，66.5(d)， 69.0(d)?69.9(d).70.6(d) ,72.7(d) ,73.0(d) ,74.1(d).76.6( d)，77.3(d)，77.5(d)，82.0(d)，83.9(d)，87.4(d)，90.5(d)，10 1 .3(d) 5 106.8(d), 129.1(d), 13 0. 1(d) ,140.5(d), 150.2(8), 163.3(s)，168.7(s)，169.2(s)，170.1(s)，170.7(s)，171.1(s)· 1 7 1 . g ( s). 1 7 3.6 (s) ppm 11) 高速液體色層分析法： 管柱：CAPCELLPAK C18UG120,4.6 (/) X 1 5 0mm (資生 堂股份有限公司製） •溶劑：含有10mM重碳酸銨之40%乙腈水溶液 流速：1 .Oml/分鐘 檢出：紫外線吸收260nm 保持時間：9.3分鐘 3 〇 · —種具有下列物理化學性狀之化合物或其鹽， 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞楓，不溶於氯仿 3) 分子式：C55H85N5 02 3 4) 分子量：1171(以FAB質譜法測定） -89- 200414902 5) 依高分解能FAB質譜法測定之精密質量’ [Μ + ΗΓ如下 列表示： 實測値：1 172·5 7 04 計算値：1172.5713 6) 紫外線吸收光譜： 於甲醇中測定紫外光吸收光譜，如下所不極大吸收表 示： 263ηχη(ε9100) 7) 旋光度： 於甲醇中測定旋光度，如下列所示値表示： [a ]D29 : +6.3。（ C〇.2 ) 8) 紅外線吸收光譜： 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下 列所示之極大吸收表示 3403，2927，2855，1 738，1691，163 1，1466,1385,1273，"61， 1 104,1014,961cm-1 9) iH-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞楓（2 49ppm) 測疋’以下所不爲其1 Η -核磁共振光譜： 〇.84(6H,t)，〇.92(3H，d，J = 5.9Hz)，1.2.1 .3(1 6Η，χη)，1.42(1Η， m)，1.55(2H，m)，1.71(lH，m)，2.0(3H，m)，2.14(2H，m)，2.26 (3H，s)，2.3(3H5m)，2.4 1(lH，m)，2.47(2H，m)，2.6(4H，m),2· 80(1H? dd,J = 6.9,13.7Hz)52.92(3H5s)?2.93(1 H5br.m)53.〇l (lH，dd，J = 2.9，13.7Hz)，3.27(lH，t，J = 9.3HZ)，3.36(3H，s)，3. 200414902 37(3H，s)，3 .38(1 H，m)，3.40(lH，m)，3.53(1 H，t，J = 2.4Hz)，3· 86( 1H，d，J = 8.8Hz)53.9(2H，m)，3.97(1 H，m),4· 13(lH，m)，4. 18(2H，m)，4.96(lH，dd，J = 2.9,9.3Hz)，5.11(lH，m)，5.38(2H， m)，5.66(lH，d，J = 8.3Hz)，5.90(lH，t，J = 5.9Hz)，5.93(lH，m)， 7.82(lH5d, J = 8.3Hz)ppm 1 0)13 C -核磁共振光譜： 重二甲亞礪中，內部標準使用重二甲亞碾（39.5ppm ) 測定’以下所示爲其i3C —核磁共振光譜： 9.5(q)514.0(q)?i9.0(q)?22.1(t)?23.9(t)524.5(t)?27.2(d),2 _ 8.7(t)，28.9(0).29.0(t)，29.1(d)，31.3(t)，33.3(t)，36.4(q),3 7.8(q)，3 9.4(t)，39.6(t)，39.8(t)，39.9(t)，40.7(t)，4 1 ·5(〇,5 6.5(t)，5 8.7(q)，60.0(q)，62.3(d)，66.6(d)，69.1(d)，70.0(d)， 70.7(d)，72.7(d)，73.0(d)，74.1(d)，76.6(d)，77.3(d)，77.6 (d),82.0(d),84.0(d),87.4(d),90.4(d), 101.3(d),106.8 (d)5 1 40.5(d)，1 5 0.2(s)，163.3 (s)，168.5 (s).169.3 (s)5 170· l(s)， 170.6(s)517 1.1(s)5171.8(s)?173.5(s)ppm 1 1)高速液體色層分析法： φ 管柱：CAPCELLPAK C18UG120,4.6px 150mm (資生堂 股份有限公司製） 溶劑：含有10mM重碳酸銨之40%乙腈水溶液 流速：1 . 0 m 1 /分鐘 檢出：紫外線吸收2 6 0 n m 保持時間：9.8分鐘 3 1 ·—種具有下列物理化學性狀之化合物或#鹽， -91- 200414902 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞楓，不溶於氯仿 3) 分子式：C55H85N5 02 3 4) 分子量：1183(以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[M + H] +如下 列表示： 實測値：1 1 84.5 723 計算値：1 1 8 4 · 5 7 1 4 6) 紫外線吸收光譜： _ 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表 示： 263nm( ε 8100) 7) 旋光度：於甲醇中測定旋光度，如下列所示値表示： [a ]D29 : +6.5 ° ( c0.2 ) 8) 紅外線吸收光譜： 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下 列所示之極大吸收表示： φ 3403,2927,2855, 1 738,1690,1631,1466,1385,1273，il62 1 1 04,1 0 1 5,962cm-1 WH-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞珮（2.49Ppm ) 測定，以下所示爲其1Η-核磁共振光譜： 0.84(6H，t)，0.9 1(3H，d，J = 6.〇Hz)，1.2-1.3(12H，m)，l.42(1H m)，1.7 0(lH，m)，2.0(5H5m)，2.14(2H，m)，2.26(3H，s),2 3(4 200414902 H，m),2.42(lH，m),2.5(2H，m)，2.6(4H,m),2.80(lH，dd，J = 6· 8，12.8Hz)，2.9 1(3H,s)，2.95(lH，br.m)，3.0 1(lH，dd，J = 2.6，l 2.8Hz)，3.27(lH，t，J = 9.0Hz)，3.36(3H，s)，3.37(3H，s)，3.4(2 H，m)，3 .53(1 H，m)，3.85(1 H，d，J = 8.1Hz)，3.9(2H，m)，3.96(1 H，m)54.13(lH，m)，4.19(2H，m).4.96(lH，dd，J = 2.6,9.4Hz)， 5. 13(lH，m)，5.30(1 H，dt，J = 7.3,9.8Hz)，5.38(2H，m)，5.47(l H，dt，J = 7.3,9.8Hz)，5.66(lH，d，J = 8.1Hz)，5.90(lH，t，J = 5.6H z)，5.93(lH,m)，7.82(lH，d，J = 8.1Hz)ppm 10)13c-核磁共振光譜： _ 重二甲亞楓中，內部標準使用重二甲亞楓（39.5ppm) 測定，以下所示爲其13 C -核磁共振光譜： 9.5(q)，14.0(q)，19.0(q)，22.1(t)，23.9(t)，2 6.7(t)，27.1(d)，2 8.7(t)，28.7(t).28.9(t)，28.9(t)，29.0(t)，29.0(t)，29.1(t)，3 1· 3(t),33 · 1 (t)，36.4( q)，37.8( q)，3 8.2(t)，39.8(t)，39·9(〇，40· 2(t)，40.7(t)，41.5(t)，56.6(t)，58.7(q)，60.0(q)，62.3(d)，66. 5(d)，69· 1(d)，69· 8(d)，70.7(d),72.7(d)，73 ·0((!)，74· 1(d)，7 6.6(d)，77.3(d)，77.5(d)，82.0(d)，84.0(d)，87.4(d)，90.5(d)， ® 1 01.3(d), 1 06.8 (d)，123.6(d)，133. 1(d)，140.5(d)，150.2(s)，163.3(s)，168.6 (s)，169.3(s)，170.2(s)，170.6(s)，171.0(s),171.8(s) ,173.5( s)ppm 1 1)高速液體色層分析法： 管柱：c APCELLPAK C18UG120,4.6 φ X 1 50mm (資生堂 股份有限公司製） -93- 200414902 溶劑：含有10mM重碳酸銨之40%乙腈水溶液 流速：1.0ml/分鐘 檢出：紫外線吸收260nm 保持時間：10.9分鐘 3 2 . —種具有下列物理化學性狀之化合物或其鹽， 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞楓，不溶於氯仿 3) 分子式：C57H87N5 02 3 4) 分子量：1 209(以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[M + H] +如下 列表示： 實測値：1 2 1 0 · 5 8 6 7 計算値：1210.5870 6) 紫外線吸收光譜： 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表 示： 263nm( ε 9900) 7) 旋光度： 於甲醇中測定旋光度，如下列所示値表示： [a ]D29 : +13.2 ° ( c0.2 ) 8) 紅外線吸收光譜： 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下 列所示之極大吸收表示_· 3383,295 7,2930，1738，1695,1629,1464，1 384，1273，1 161， 200414902 1 104,1014,960cm·1 9) 核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞碾（2.49ppm ) 測定，以下所示爲其1Η-核磁共振光譜： 〇.84(6H，t)，0.9 1(3H，d，J = 6.0Hz),1.2-1.3(8H,m)，1.42(lH， m)，1.57(2H，m)，1.70(lH，m)，2.0(7H，m)，2.11(lH，m)，2.17 (lH，m)，2.26(3H，s)，2.3(3H，m)，2.4(3H，m)，2.5-2.6(4H，m)， 2.7 1(2H5dd，J = 6.OHz)，2.80(lH，dd，J = 7.0，12.8Hz)，2.9 1(3 H，s)，2.93(lH，br.m)，2.98(lH，dd，J = 2.7，12.8Hz)，3.26(lH， t，J = 9.2Hz)，3.36(3H，s)，3.37(3H，s)，3.4(2H，m)，3.52(lH, m)，3.84(lH，d，J = 8.1Hz)，3.9(2H，m)，3.94(lH，m)，4.14(lH， m)，4.2(2H，m)，4.96(lH，dd，J = 2.9,9.5Hz)，5.12(lH，m)，5.30 (4H，m)，5.37(2H，m)，5.66(lH，d，J = 8.1Hz)，5.90(lH，t，J = 5.9 Hz)，5.93(lH，m)，7.82(lH，d,J = 8.1Hz)ppm 10) 13c-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞碾（39.5ppm ) 測定’以下所示爲其-核磁共振光譜： 9.4(q)，l 3.9(q)，i9.0(q)，22.0(t)，23.9(t)，24.6(t)，25.2(t)52 6.3(t)，26.6(t)，27.1(d)，28.7(t)，29.3(t)，29.4(t)，30.9(t)，3 2.9(t)，36.4(q)，37.8(q)，38.8(t)，39.8(t)，39.9(t)，40.2(t)，4 〇·7(0,4 1 .5(t)，5 6.6(t)，5 8.7(q)，60.0(q)，62.3(d)，66.7(d)，6 9.0(d)，69.9(d)，70.6( d)，7 2.7(d)，73.1(d)，74· 1(d)，76.6(d). 77.3(d)，7 7.4(d)，82.2(d)，83.9(d)，87.5(d)，90.5(d)，101.3 (d)，106.7(d)，127.6(d)，128.2(d)，129.2(d)，129.8(d)，140.5 -95- 200414902 (d)，150.3(s)，163.3(s)，168.6(s)，169.2(s)，170.1(s)，170.8 (s)?171. l(s)?171.9(s)?173.8(s)ppm 1 1)高速液體色層分析法： 管柱·· CAPCELLPAK C18UG120,4.6px 150mm (資生堂 股份有限公司製） 溶劑：含有10mM重碳酸銨之4〇%乙腈水溶液 流速：1 .Oml/分鐘 檢出：紫外線吸收260nm 保持時間：14.8分鐘 籲 3 3 ·具有下列物理化學性狀之化合物或其鹽： 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞碾，不溶於氯仿 3) 分子式：C55H87N50 2 3 4) 分子量：1185(以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[Μ + ΗΓ如下 列表示： 實測値：1 1 8 6 · 5 8 2 8 ^ 計算値：1 1 8 6 · 5 8 7 0 6) 紫外線吸收光譜z 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表 示： 263nm(£ 11000) 7) 旋光度： 於甲醇中測定旋光度，如下列所示値表示： -96- 200414902 [α ]D” ： +;i3.9° ( c0.2 ) 8 )紅外線吸收光譜： 以溴化鉀（KB I·)錠劑法測定之紅外線吸收光譜以下列 所示之極大吸收表示： 3393,2953,2927,1 738,1695,1632,1466,1 384,1273,1 162， 1 1 04,1 0 1 4,960cm·1 9)4-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞楓（2.49ppm ) 測定，以下所示爲其1Η-核磁共振光譜·· _ 0.83(6H，t，J = 6.6Hz)，0.84(3H,t，J = 7.3Hz)，0.92(3H，d，J = 6.2 Hz)，1.12(2H，dt，J = 6.6Hz)，l，2-1.3(12H，m)，1.4-1.5(2H，m)， 1.55(2H，m)，1.70(lH，m)，2.0(3H，m),2.11(lH，m)，2.17(lH， m)，2.26(3H，s)，2.3(3H，m)，2.4-2.5(3H，m)，2.5-2.6(3H，m)， 2.7 9(1 H，dd，J = 6.6，12.8Hz)，2.9 1(3H，s)，2.94(l H，bi*.m)52.9 9(lH，dd，J = 2.8，12.8Hz)53.27(lH，t，J = 9.3Hz)，3.36(3H，s)，3. 37(3H，s)，3,40(2H，m)，3.52(lH，m)，3.84(lH，d，J = 8.8Hz)，3. 87(2H，ni)53.94(lH，m)，4.13(lH，m)，4.19(2H，m),4.96(lH5d · d，J = 2.9,9.2Hz)，5.11(lH，m)，5.3 7(2H，m)，5.37(2H,m)，5.66 (lH，d，J = 8.1Hz)，5.90(lH，t，J = 5.5Hz)，5.93(lH，m)，7.83(lH， d, J = 8 .lHz)ppm i 〇)13 c -核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞楓（39.5ppm) 測定’以下所示爲其-核磁共振光譜： 9*5(q)?19.〇(q)922.5(q))23.9(t)?24.5(t),26.8(t)527.1 (d)?2 -97- 200414902 7.4(d)528.7(t)，28.9(d)，28.9(d)，29.3(t)，29.3(t)，29.5(t)，3 3.2(t)，36.4(q)，3 7.8(q)，3 8.5(t)，3 8.8(t)，39.8(t)，39.9(t),40. 1 (t)，40.2(t)，4 1 .5(t)，56.6(t),5 8.7(q)560.0(q)562.3(d)，67. 3(d)，69· 1(d)，70.0(d)，70.6(d)，72.7(d)，73· 1(d)，74· 1(d)，76. 6(d)，77.2(d)，77.5(d)，82.2(d)，83.9(d)，87.6(d)，90.5(d)，10 1 .3(d)，1 06.6(d)，140.5(d)，150.3(s)，163.3(s)，l68.5(s)，169. 3(s)，170.1 (s)，170.8(s)，171· l(s)，172.0(s)，173.8(s)ppm 11)高速液體色層分析法： 管柱：CAPCELLPAK C18UG120,4.6 φ X 1 50mxn (資生堂鲁 股份有限公司製） 溶劑：含有10mM重碳酸銨之42%乙腈水溶液 流速：1 .Oml/分鐘 檢出：紫外線吸收260nm 保持時間：9.5分鐘 34.—種具有下列物理化學性狀之化合物或其鹽： 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞®，不溶於氯仿 · 3) 分子式：C56H87N5023 4) 分子量：1197(以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[M + H] +如下列 表示： 實測値：1 1 9 8.5 8 7 5 計算値：1 1 9 8.5 8 7 0 6) 紫外線吸收光譜： -98- 200414902 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表 示： 2 6 3 nm ( ε 8 7 0 0) 7) 旋光度：於甲醇中測定旋光度，如下列所示値表示： [a]D29 : — 6.8 ( c 0.2 ) 8) 紅外線吸收光譜= 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下列 所示之極大吸收表示： 3414,2928,2856,1738,1689, 1632,1465,1394,1273,1 161， 1 126，1 1 04,1 0 1 4,959cm·1 Ρ)1：»-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞碾（2.49ppm) 測定，以下所示爲其1Η-核磁共振光譜： 0.84(6H，t)，0.92(3H，d，J = 6.2Hz)，l，2-1.3(12H，m)，1.42(lH， m)，1.57(2H5m)，1.71(lH，ni)，2.0(7H，m)，2.11(1 H, m)，2.17(1 H，m)，2.25(3H，s)，2.3(3H，m),2.4 1(lH，m),2.43(2H,m)，2.6 (4H，m) ,2.80(1 H，dd，J = 6.6，13.6Hz)，2.91(3H，s)，2.93(lH，m)， 2.98(1 H，dd，3.3，13·6Ηζ)，3.27(lH，t，J = 9.5Hz)，3.36(3H，s)，3· 37(3H，s)，3.4(2H，m)53.52(m，m)，3.84(lH，d，J = 8.4Hz)，3.87 (2H，m)，3.94(lH，m)，4.13(lH，m)，4.19(2H，m)，4.96(lH，dd，J = 3.3,9.5Hz)，5.90(lH，t，J = 5.9Hz)，5.37(2H，m)，5.66(lH，d，J = 8」Hz)，5.90(lH，t，J = 5.9Hz)，5.93(lH，m)，7.83(lH，d，J = 8.1H z)ppm 1 0 ) 13 C -核磁共振光譜： -99- 200414902 重二甲亞楓中，內部標準使用重二甲亞碾（39.5ppm) 測定’以下所示爲其i3C -核磁共振光譜： 9.5(q)5l4.〇(q)5 ! 9.0( q) 5 2 2. l(q),23.9( t),24.8(t),26.3(t)526. 6(q)，27.1(d)528.6(t)，28.6(t)，29.0(t)，29.1(t)，29.3(t)，3 1.3 (t),32.9(t)，36.4( q)，37.8( q)，38.9(t)，39.8(t)，39.9(t)，40.2 (t)，40.7(t)，4 1 .5 (t)，56.6(t)，5 8.7(q)，60.0(q)，62.3(d)，66.7 (d)，69.0(d)，69· 9(d)，70.5(d)，72.7(d)，73.2(d)，74.1(d)，76.6 (d)，7 7.2(d)，77.5(d)，82.2(d)，83.9(d),89.1(d)，90.5 (d)，10 1.3(d)，106.6(d)，129.1(d)，130.1(d)，140.6(d)，150.3(s)，163. φ 3(s)，168.4(s)，169.2(s)，170.1(s)，170.8(s)，171.1(s)，172.0 (s)，173.8(s)ppm 1 1)高速液體色層分析法： 管柱：CAPCELLPAK C18UG120,4.6 φ X 1 50mm (資生堂 股份有限公司製） 溶劑：含有10mM重碳酸銨之42%乙腈水溶液 流速：1.0ml /分鐘 檢出：紫外線吸收2 6 0 n m _ 保持時間：10.2分鐘 3 5 · —種具有下列物理化學性狀之化合物或其鹽： 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞碾，不溶於氯仿 3) 分子式：C55H87N5023 4) 分子量：1185(以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[m + h] +如下 -100- 200414902 列表示： 實測値：1 1 8 6 · 5 9 1 2 計算値：1 1 8 6 · 5 8 7 0 6) 紫外線吸收光譜： 於甲醇中測.定紫外光吸收光譜，如下所示極大吸收表 不： 263nm( ε 3600) 7) 旋光度： 於甲醇中測定旋光度，如下列所示値表示： 鲁 [a ]D29 : + 4.3。（ c0.5 ) 8) 紅外線吸收光譜： 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下列 所示之極大吸收表示： 3371，2926,2855,1738,1691，1628,1466,1 384,1273,1 161， 1 1 04,1 0 1 6,962cm*1 9) 屮-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞楓（2.05ppm ) ® 測定’以下所示爲其iH-核磁共振光譜： 〇.84(6H，t)，〇.92(3H，d，J = 5.5Hz)，1.2-1.3(18H，m)，1.42(lH，m)，1.55(2H，m),1.70(lH，m)，2.0(3H， m)，2.14(2H，m)，2.26(3H，s)，2.3(3H，m)，2.41 (lH，m)，2.47(2 H，m)，2.6(4H，m)，2.80(lH，dd，J = 6.2，13.6Hz)，2.92(3H，s)，2· 94(lH?br.m)53.01(lH.dd5J = 2.2?13.6Hz)53.27(lH5t5J = 8.8 H2)，3.30(3H，5)，3.37(3H55)，3.40(2H，m)，3.53(lH，m)，3.8 -101- 200414902 6(lH，d，J = 9.5Hz)，3.9(3H，mM.13(lH，m),4.19(2H，m)，4.9 6(lH，dd，J=1.8,9.2Hz)，5.11(lH，m)，5.37(2H，m)，5.65(lH，d, J = 7.7Hz)?5.90(lH?t?J = 5.0Hz)?5.93(lH,m)?7.81(lH?d?J = 7. 7 H z) p p m 1 0 ) 13 c -核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞楓（39.5ppm) 測定，以下所示爲其13C -核磁共振光譜： 9.5(q)，14.0(q)，19.0(q)，22.1(t)，23.9(t)，24.5(t)，27.2(d)， 28.7(t)，28.7(0)，28.9(t)，28.9(t)，29.0(t)，29.0(t)，29.1(d). 3 1.3(t),33.3(t)，36.4(q)，37.8(q)，3 8.8(t)，39.8(t)，39.9(t)， 40.2(t),40.7(t)，4 1.5(t)，5 6.S(t),5 8.7(q)，60.0(q)，62.4(d )，66.5(d)，69.0(d)，70.6(d)，72.7(d)，72.9(d)，74.1(d)，76. 6(d)，77.3(d)，77.5(d)，82.0(d)，84.0(d)，87.3(d)，90.4(d)， 101.3(d)，106.9(d)，140.5(d)，1 50.2(s)，163.3(s)，168.7(s)， 169.3(s)，170.1(s)，170.6(s)，171.1(s)，171.8(s)，173.5(s) ppm 1 1)高速液體色層分析法： 管柱：C APCELLPAK C18UG120,4.6 ¢) x 1 50mm (資生 堂股份有限公司製） 溶劑：含有10mM重碳酸銨之42%乙腈水溶液 流速：1.0ml/分鐘 檢出：紫外線吸收260nm 保持時間：1 1 . 2分鐘 3 6. —種具有下列物理化學性狀之化合物或其鹽， -102- 200414902 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於水，不溶於氯仿 3) 分子式： 4) 分子量：543 (以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[Μ + ΗΓ如下 列表示： 實測値：5 4 4.2 2 4 0 計算値：544.2255 6) 紫外線吸收光譜： _ 於水中測定紫外光吸收光譜，如下所示極大吸收表 示： 2 6 3 nm( ε 8 70 0) 7) 旋光度： 於水中測定旋光度，如下列所示値表示： [a ]D2 9 : + 6 2.7 ° ( c0.2) 8) 紅外線吸收光譜z 以溴化鉀（KB 〇錠劑法測定之紅外線吸收光譜以下 鲁 列所示之極大吸收表示： 3393,2929,1688,1620.1468,1394,1274.1094,1065,1019， 9 6 2 cm ~ 1 9) 1^核磁共振光譜： 重水中，內部標準使用重水（4.75ppm )測定，以下 所示爲其1H-核磁共振光譜： 2.2 1(lH，ddd，J = 3.3,5.9，14.7Hz)，2.3- -103- 200414902 2.4(3H，m),2.44(3H，s)，2.86(lH，dd，J = 9.2，13.6Hz)，2.97( lH，d，J = 14.7Hz)，3.07(3H，s)，3.13(lH，d，J=14.7Hz)，3.24( 1 H,dd,J = 4.4，l 3.6Hz)，3.80(lH，d，J = 9.9Hz)，3.93(1 H,d，J = 6.6Hz)，4.20(lH,d，J = 5 ·1Ηζ),4.25(lH，dt，J = 7.0Hz) ,4.38(1 H，m)，4.4 1(lH，d,J = 9.9Hz)，4.44(lH，m)，5.56(lH，dd，J = 3.3, 5 ·9Ηζ)，5.8 l(lH，d，J = 8.1Hz)，6.00(lH，t，J = 5.5Hz)，7·74(1 H， d，J = 8.1Hz)ppm 10) 13c-核磁共振光譜： 重水中，內部標準使用二噚烷（66.5PPm )測定，以 下所示爲其-核磁共振光譜： 36.4(q)，38.6(q)，38.7(t)，40.1(t)，40.4(t)，58.6(t)，63.1(d )，6 8.7(d)，69.1(d)，69.4(d)，7 1.8(d)，76.9(d)，8 1.6(d)，85. 0(d),85.3(d), 101.3(d),109.0(d), 142.2(d),15 1.4(5),166. 5 (5 ),1 7 2.3 (5 ),1 7 3.5 (5 )ppm 11) 高速液體色層分析法： 管柱：CAPCELLPAK C18UG120,4.6 0 X 1 50mm (資生堂 股份有限公司製） 溶劑：10mM重碳酸銨 流速：1 . 〇 m 1 /分鐘 檢出：紫外線吸收260nm 保持時間：9 · 2分鐘 3 7·—種具有下列物理化學性狀之化合物或其鹽： 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞碾，不溶於氯仿 -104- 200414902 3) 分子式：C22H31N5O10 4) 分子量：5 2 5 (以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[M + H] +如下 列表示： 實測値：5 2 6.2 1 5 3 計算値：526.9149 6) 紫外線吸收光譜： 於水中測定紫外光吸收光譜，如下所示極大吸收表 示·· 260nm( £ 8700) 7) 旋光度： 於水中測定旋光度，如下列所示値表示： [a ]D2 9 : + 6 5.5。（ c0.2 ) 8 )紅外線吸收光譜： 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下 列所示之極大吸收表示： 3403，2953，1 690,1633,1467,1382,1361，1 274，1098，1067, 1 0 1 3.9 64cm'1 9) iH-核磁共振光譜： 重水中，內部標準使用重水（4.7 5PPm)測定，以下 所示爲其1H-核磁共振光譜： 2.2- 2 ·4(4Η，m)，2·43(3Η，s)，2.86(1 H，dd，J = 9.9,13.6Hz)，2.92(1 H，dd，J = 6.6，12.7Hz),2.97(3H，s)，3.23(lH，dd，J = 4.0，i36 -105· 200414902 Hz)53.3 2(lH，dd，J = 7.3, 12·7Ηζ)，3.87(1 H，d，J = 9.5Hz)，4.0 8(lH，m)，4.18(lH，m)，4.3 1(lH，dt，J = 5.8Hz)，4.35(lH，m)，4. 38(lH，m)，5.56(lH，dd，J = 2.6,5.9Hz)，5.80(lH，d，J = 8.1Hz )，6.06(1 H，t，J = 5.9Hz)，6.47(1 H，dd，J = 6 ·6,7.3Hz)，7.64(l H，d，J = 8.1Hz)ppm 10) 13 C -核磁共振光譜： 重水中，內部標準使用二噚烷（66.5PPm)測定，以 下所示爲其-核磁共振光譜： 32.7(q)，38.6(t)，40.0(q)，40.5(t)，40.9(t)，5 1.0(t)，63.2(d)， 69.8(d)，71.7(d)，76.7(d)，82.4(d)，85.2(d)，85.6(d)，101.8( d)5 107.7(d)，123.1(d)，141.4(d)，144.2(s)，152.4(s)，167.7 (s),168.6(s)，171.0(s)ppm 11) 高速液體色層分析法： 管柱：CAPCELLPAK C18UG120,4.6<;6x 150mm (資生堂 股份有限公司製） 溶劑：含有1 〇 Π1Μ重碳酸銨之3 %乙腈水溶液 流速：1.0ml/分鐘 檢出：紫外線吸收2 60nm 保持時間：13.0分鐘 3 8 · —種具有下列物理化學性狀之化合物或其鹽， 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞®，不溶於氯仿 3) 分子式：C42H67N5016 4) 分子量：897(以FAB質譜法測定） -106- 200414902 5) 依高分解能FAB質譜法測定之精密質量，[Μ + ΗΓ如下 列表示：實測値：8 9 8.46 6 9計算値：89 8.466 1 6) 紫外線吸收光譜： 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表 示： 263nm( ε 7500) 7) 旋光度：於甲醇中測定旋光度，如下列所示値表示： [a ]d29 ·· + 19.8 ° ( c0.2 ) 8) 紅外線吸收光譜： $ 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下 列所示之極大吸收表示： 3394,2926,2855,1 737, 1 691，1629,1467,1397,1274,12〇3 1 131,1 094,1 0 1 3,962cm-1 9) iH-核磁共振光譜： 重二甲亞碾中，內部標準使用重二甲亞楓（2·49Ρρη〇 測定’以下所示爲其^Η-核磁共振光譜： 0.84(3H，t，J = 7.1Hz)，0.88(3H,d，J = 6.3Hz)，1.2- # 1.3(18H，m)，1.57(2H，m)，1.9-2.2(8H，m)，2.24(3H，s)，2.43(lH，dd，J = 5.5- 15.1Hz)，2.54(lH，dd，J = 8.2，15.4Hz)，2.66(lH，dd，J = 4.4，i 5.4Hz)，2.7 4(lH，dd，J = 6.3，12.6Hz)，2.91(3H，s)，2.93(iH m)，2.99(lH，dd,J = 3.8，12.6Hz)，3.30(lH，m)，3.83(lH5d，j = 9.1Hz)53.9- 4.0(3H，m)，4.12(lH，dt，J = 5.2,5.5Hz),4.2(2H，m)，5.〇8(1H -107- 200414902 m )55.38(2H?m)55.67(1 H?d,J = 8.0Hz),5.90(1 H?t?J = 6.0Hz)? 7.8l(lH，d.〇Hz)，5.90(lH，t5J = 6.0Hz)，7.8 1(lH，d，J = 8. 0)ppm 1〇) I3C_核磁共振光譜·· 重二甲亞®中，內部標準使用重二甲亞楓（39.5PPm) 測定’以下所示爲其13C -核磁共振光譜： 14.0U)，19.4(q)，22.1(t)，24.6(t)，27.1(d)，28.7(t)，28.7(t )，28.9(t)，29.〇(t)，3i.3(t)，33.2(t)，36.4(q)，3 7.8(q)，3 8.9( t)，39.8(t)，39.9(t)，40.1(t),40.4(t)，4 1.5(t)，5 6.6(t)，62.3( d)’66.6(d)，69 .1(d)，69.9(d)，70.7(d)，72.8(d)，77.6(d)，82. 〇(d),83.9(d)，87.4(d)，101.3(d)，107.0(d)，140.5(d)，150. 2(d)，163.3(s)，168.5(s)，169.3(s)，170.7(s)，171.5(s)，173· 8 (s)ppm 1 1) 高速液體色層分析法： 管柱：CAPCELLPAK C18UG120,4.64x 150mm (資生 堂股份有限公司製） 溶劑：含有〇·2%三乙基胺-磷酸緩衝液，調節pH33之 5 5 %乙腈水溶液 流速：1 . 〇 m 1 /分鐘 檢出：紫外線吸收2 6 0 n m 保持時間：4.0分鐘 3 9·—種具有下列物理化學性狀之化合物或其鹽， i )物質之性狀：無色粉末狀物質 2)溶解性：可溶於甲醇、二甲亞碾，不溶於氯仿 -108- 200414902 3) 分子式· C54H85N5023 4) 分子量：U71(以FAB質譜法測定） 5 )依高分解能F A B質|普法測定之精密質量’ [M + Η ] +如下 列表示： 實測値：1 1 72.5 7 3 1 計算値：1 1 7 2 · 5 7 1 3 6) 紫外線吸收光譜： 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表 示： 263nm( ε 1 0400) 7) 旋光度： 於甲醇中測定旋光度，如下列所示値表示： [a ]D29 : + 1 0·6 c ( c0.3 ) 8 )紅外線吸收光譜： 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以下 列所示之極大吸收表示： 3403,2926,2855,1 739,1695,1628,1467,1 384,1 273,1 162, 1 103,1013,966cm'1 9) 1H-核磁共振光譜： 重二甲亞珮中，內部標準使用重二甲亞碾（2.49Ppm) 測定’以下所示爲其ιΗ-核磁共振光譜： 0.83(3H.t，J = 6.6Hz)，0,9 1(3H，d，J = 6.3Hz)，1.17(3H，d，J = 6 0Hz)，l.2-1.3(18H，m)，1.55(2H，m)，1.9-2.1(3H，m)，2,13(2 H.m)，2.26(3H，s)，2.3-2.4(3H,m)，2.4 1(lH，dd，J = 6.0，l5.4 •109- 200414902 Hz)，2.47(2H,m)，2.6(4H，m)，2,80(lH，dd，J = 5.8，12.6Hz)，2· 92(3H，s)，2.9-3.0(2H，m)，3.20(lH，dd，J = 9.0,9.6Hz)，3.32 (lH，m)，3.36(3H，s)，3.37(lH，m)，3.38(3H，s)，3.41(lH，m)， 3.52(1 H，m)，3.5 9(lH,dq，J = 6.0,9.0Hz)，3.80(lH，d，J = 8.5 Hz)，3.9(2H，m)，3.94(lH，d，J = 3.3Hz)，4.10(lH，m)，4.21(2 H，m)，4.94(lH，dd，J = 3.0,9.6Hz),5.11(lH，m)，5.37(2H，m)5 5.66(1 H，d，J = 8.0Hz)，5.89(lH，t，J = 5.5Hz)，5.90(lH，d，J=l, 4Hz)，7.8 1(lH，d，J = 8.0Hz)ppm 10) 13c-核磁共振光譜： 重二甲亞碾中，內部標準使用二甲亞碾（39.5ppm) 測定，以下所示爲其13C -核磁共振光譜： 1 4.0(q)，17.7(q)，19.0(q)，22. l(t)，24.6(t)，27. l(d)，28.7(t )，28.7(t)，28.9(t)，29.0(t)，29.1(t)，3 1.3(t)，3 3.3(t)，36.3( q)，37.8(q)，3 8.8(t)，39.8(t).39.9(t)，40.0(t)，40.2(t)，4 1.4 (t)，56.6(t)，5 8.7(q)，60.2(q)，62.4(d)，66.4(d)，69.0(d)，69. 6(d)，70.0(d)，70.5(d)，72.5(d)，72.8(d)，76.7(d)，77.4(d)， 79.2(d)，82.0(d)，84.0(d)，87.2(d)，90.4(d)，101.2(d)，107· 0(d)，140.4(d)，150.2(5)，163.3(5)，169.0(5)，169.3(5)，17 0.2(5). 170.7(5),171.2(5), 171.8(5),1 73.5(5)ppm 11) 高速液體色層分析法： 管柱：CAPCELLPAK C18UG120,4.6 φ X 1 50mm (資生 堂股份有限公司製） 溶劑：含有0.2%三乙基胺-磷酸緩衝液，調節ρΗ3·3之 5 5 %乙腈水溶液 -110- 200414902 流速：1 .0ml/分鐘 檢出：紫外線吸收260nm 保持時間：6.5分鐘 4〇·—種具有下列物理化學性狀之化合物或其鹽， 1) 物質之性狀：無色粉末狀物質 2) 溶解性：可溶於甲醇、二甲亞楓，不溶於氯仿 3) 分子式：C54H85N5 02 3 4) 分子量：1171(以FAB質譜法測定） 5) 依高分解能FAB質譜法測定之精密質量，[M + H] +如下 列表示： 實測値：1 1 7 2.5 7 3 1 計算値：1 1 7 2.5 7 1 3 6) 紫外線吸收光譜： 於甲醇中測定紫外光吸收光譜，如下所示極大吸收表 示： 262nm(ε 11000) 7) 旋光度： 於甲醇中測定旋光度，如下列所示値表示： [a ]D29 : + 14.2 ° ( c0.2 ) 8) 紅外線吸收光譜： 以溴化鉀（KBr )錠劑法測定之紅外線吸收光譜以τ 列所示之極大吸收表示： 3368，2927，2856，1735,1707,1674,1 65 1，161 5,1466，1378 1 276,1 1 6 1,1 1 04,95 1 cm·1 -111- 200414902 9 ) 1Η -核磁共振光譜： 重甲醇中，內部標準使用重甲醇（4.7 8ppm)測定， 以下所示爲其iH-核磁共振光譜： 0.76(3H，t，J = 7.0Hz)，0.8 1(3H5d，J = 7.4Hz)，0.90(3H，d，J = 6. 4Hz)，1.2-1.3(1 8H，m)，1.37(lH，ni),1.51(2H，m)，1.68(lH, m)，2.1-2.2(4H，m)，2.2-2.4(5H,m)，2.42(3H，s),2.5-2.6(6 H，m)，2.85(lH，dd，J = 8.3，13.4Hz)，3.0(2H，br，d)，3.09(lH， dd，J = 4.0，13.4Hz)，3.22(lH，dd，J = 9.0,9.0Hz)，3.32(3H，s)， 3·34(3Η，s)，3.37(1 H，m)，3.49(1 H，dd，J = 2.3,3.3Hz)，3.8(1 H，br，d)，4.0(2H，m)，4.10(lH，dd，J = 6.0,6.4Hz)，4.2(2H，m)， 4·26(1 H，dd，J = 2.0,8 ·7Ηζ)，4.96( lH，dd，J = 3.3,9.0Hz)，5.1 4(1H，m)，5.2-5.4(1H，br m)，5.41 (lH，t，J = 4.9Hz)，5.94(1 H， t，J = 5.0Hz)，7.71(lH，d，J = 8.0Hz)ppm 10) 13c-核磁共振光譜： 重二甲亞碾中，內部標準使用重甲醇（49.0ppm )測 定，以下所示爲其13C -核磁共振光譜： 1 0· 1 (q)，1 4.5(q)，20· l(q)，23.8(t)，25.6( t)，26.3( t)，28.9(d)， 29.8(t)，30.3(t)，30.4(t)，30.5(t)，30.6(t)，3 0.7(t)，30.8(t), 3 3.9(t)，3 5.3(t)，37.0(q)，40.7(t)，40.8(t)541.2(t)，4 1.5(t)， 58.4(t)，59.7(q)，61.0(q)，62.6(d)，66.3(d)，68.8(d)，69.4(d )，69.7(d)，72.0(d)，72.9(d)，73.0(d)，74.8(d),76.2(d)，78.6 (d)，79.3(d)，84.2(d)，86.6(d)，87.1(d)，92.4(d)，103.3(d)，l 09.1(d)，144.3(d)，141.9(s)，164.4(s)，165.8(s)，170.1(s)，l 71.0(s),172.2(s)，173.6(s)，175.9(s)ppm •112· 200414902 11) 高速液體色層分析法： 目柱· CAPCELLPAK C18UG12O,4.60x 150mm (資生堂 股份有限公司製） 溶劑：含有0.2%三乙基胺-磷酸緩衝液，pH 3.3之55% 乙腈水溶液調節 流速：1 · 0 m 1 /分鐘 檢出：紫外線吸收260nm 保持時間：7.0分鐘 4 1 . 一種如申請專利範圍第1至4 〇項中任1項化合物之製造方 法’其特徵爲培養屬於鏈孢囊菌屬（Streptosp o r an gi um ) 之生產申請專利範圍第1至4 0項中任1項化合物之生產 菌’自培養物中收取申請專利範圍第1至4 〇項中任i項之 化合物。 42·如申請專利範圍第41項之製造方法，其中該培養係於含 脂肪酸之培養基中進行。 4 3 ·如申請專利範圍第4 2項之製造方法，其中該脂肪酸爲碳 數10至20之直鏈狀飽和脂肪酸。 44 ·如申請專利範圍第4 2項之製造方法，其中脂肪酸爲碳數 12至18之直鏈狀飽和脂肪酸。 4 5 ·如申請專利範圍第4 1至4 4項中任1項之製造方法，其中 屬於鏈孢囊菌屬（Streptosporangium)之生產申請專利 範圍第1至4 〇項中任1項之化合物之生產菌爲鏈孢囊菌 (Streptosporangium sp.) S AN K6 0 5 0 1 (F E RM B P - 7 9 8 4)。 46·—種生產申請專利範圍第1至40項中任丨項化合物之微生 200414902 物，其屬於鏈孢囊菌屬（Streptosporangium sp)。 47· —種鏈孢囊菌（Streptosporangium sp)SANK6〇501(FERM BP-7984)。 4 8 . —種製造申請專利範圍第2 5或3 6項化合物之方法，其係 將申請專利範圍第1至1 9、2 9至3 5及3 8至3 9中任1項之化 合物水解或還原。 49· 一種製造申請專利範圍第26或3 7項化合物之方法，其係 將申請專利範圍第1至1 9、2 9至3 5及3 8至3 9中任1項之化 合物水解或還原。 5 〇·—種製造申請專利範圍第27項化合物之方法，其係將申 請專利範圍第2〇至24及4 0項中任1項之化合物水解或還 原。 5 1 · —種製造申請專利範圍第2 8項化合物之方法，其係將申 請專利範圍第2 〇至2 4及4 0項中任1項之化合物水解或還 原。 5 2 · —種醫樂組成物，其含有申請專利範圍第丨至4 〇項中任工 項之化合物或其藥理學上容許鹽爲有效成分。 5 3 ·如申請專利範圍第5 3項之醫藥組成物，其爲一種抗菌 劑。 54·—種細菌感染症之治療方法，其包含將有效量之申請專 利範圍第1至40項中任丨項之化合物或其藥理學上容許鹽 投與病患。 5 5·—種如申g靑專利範圍第2至4〇項中任i項之化合物或其藥 理學上容許鹽之用途，其用於製造抗菌劑。(VIII) 〇2 9.—A compound or a salt thereof having the following physical and chemical properties, 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethyl arylene, and insoluble in chloroform 3) Molecular formula: C55H85N5 02 3 4) Molecular weight: 1183 (determined by FAB mass spectrometry) 5) Precise mass determined by high decomposition energy FAB mass spectrometry, [M + H] + as shown below: Actual measurement: 1 1 8 4.5 6 9 9 Calculated 値: 1 1 8 4.5 7 1 3 6) Ultraviolet absorption spectrum: -87- 200414902 Determine the ultraviolet light absorption spectrum in methanol, and the maximum absorption is shown as follows: 263nm (e9200) 7) Optical rotation: Determine the optical rotation in methanol Degrees, as shown below: [a] D29: +7.5 ° (c0.5) 8) Infrared absorption spectrum: The infrared absorption spectrum measured by potassium bromide (KBr) lozenge method has the maximum absorption shown below Representation: 3414, 2928, 2856, 1738, 1696,163 1, 1465,1 384,1273, il6l 1 1 27,1 1 04,1 0 1 5,9 60cm · 1 9) iH-NMR spectrum: double The internal standard is determined by heavy dimethanine (2.49ppm}), which is shown below as its 1 H-NMR Resonance spectra: 0.84 (6H, t), 0.9 1 (3H, d, J = 6.2Hz), 1.2-1.3 (10H, m), 1.42 (lH, m), 1.57 (2H, m), 1.7 1 (lH , M), 2.0 (7 H5m), 2.12 (lH, m), 2.16 (lH, m), 2.26 (3H, s), 2.3 (3H5m) 2 4 1 (lH, m), 2.46 (2H5m) 52.6 ( 4H, m), 2.80 (lH, dd, J = 6.6, l8 Hz), 2.92 (3H, s), 2.94 (lH, m), 2.98 (lH, bi * .m), 3.26 (lH t J = 9.2 Hz), 3.36 (3H5s), 3.37 (3H? S)? 3.4 (2H? M)? 3.53 (iH m), 3.83 (lH, d, J = 8.4Hz) 53.9 (3H, m), 4.13 (lH, m), 4.l9 (2H m), 4.96 (1 H, dd, J = 2.9, 9.2 Hz), 5.12 (lH, m), 5.3 (2H, m) 5 37 (2H, m), 5.65 (lH, d, J = 7.7 Hz), 5.90 (lH, t, J = 5.9HZ), 5 9 3 (lH, m), 7.82 (lH, d, J = 7.7) ppm -88- 200414902 10) 13C -Nuclear Magnetic Resonance Spectroscopy: In heavy dimethanine, the internal standard is determined using heavy dimethyfeng (39.5ppm), and its 13C is shown below.-Nuclear magnetic resonance spectrum: 9.5 (q), 14.0 (q), 19.0 (q ), 22.1 (t), 23.9 (t), 24.8 (t), 26.3 (t), 26.6 (t), 27.1 (d), 28.3 (t), 28.7 (t), 29.1 (t) , 9.2 (t), 3 1 · 2 (〇, 32.9 (t), 3 6.4 (q), 3 7.8 (q), 3 8.8 (t), 9.8 (t), 3 9.9 (t), 40. 2 (t), 40.6 (t), 41.5 (t), 56.6 (t), 8.7 (q), 60.0 (q), 62.3 (d), 66.5 (d), 69.0 (d)? 69.9 (d). 70.6 (d), 72.7 (d), 73.0 (d), 74.1 (d). 76.6 (d), 77.3 (d), 77.5 (d), 82.0 (d), 83.9 (d), 87.4 (d), 90.5 (d), 10 1 .3 (d) 5 106.8 (d), 129.1 (d), 13 0. 1 (d), 140.5 (d), 150.2 (8), 163.3 (s), 168.7 (s) , 169.2 (s), 170.1 (s), 170.7 (s), 171.1 (s) · 1 7 1. G (s). 1 7 3.6 (s) ppm 11) High-speed liquid chromatography analysis method: Column: CAPCELLPAK C18UG120,4.6 (/) X 1 50 mm (manufactured by Shiseido Co., Ltd.) • Solvent: 40% acetonitrile aqueous solution containing 10 mM ammonium bicarbonate. Flow rate: 1.0 ml / min. Detection: UV absorption at 260 nm. Hold time: 9.3 minutes. 3 〇 · —A kind of compound or its salt with the following physical and chemical properties, 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethyl sulfoxide, and insoluble in chloroform 3) Molecular formula: C55H85N5 02 3 4 ) Molecular weight: 1171 (determined by FAB mass spectrometry) -89- 200414902 5) Precise mass determined by high decomposition energy FAB mass spectrometry '[Μ + ΗΓ is as follows: Measured 値: 1 172 · 5 7 04 Calculate 値: 1172.5713 6) Ultraviolet absorption spectrum: Measure the ultraviolet light absorption spectrum in methanol, which is indicated by the following maximum absorption: 263ηχη (ε9100) 7) Optical rotation: Measure the optical rotation in methanol, as shown below: : [A] D29: +6.3. (C〇.2) 8) Infrared absorption spectrum: The infrared absorption spectrum measured by the potassium bromide (KBr) lozenge method is expressed by the maximum absorption shown below 3403, 2927, 2855, 1 738, 1691, 163 1, 1466 , 1385,1273, " 61, 1 104,1014,961cm-1 9) iH-NMR spectrum: In heavy dimethyline, the internal standard uses heavy dimethylate (2 49ppm) to measure the following: Its 1 Η-nuclear magnetic resonance spectrum: 0.84 (6H, t), 0.92 (3H, d, J = 5.9Hz), 1.2.1.3 (16Η, χη), 1.42 (1Η, m) , 1.55 (2H, m), 1.71 (lH, m), 2.0 (3H, m), 2.14 (2H, m), 2.26 (3H, s), 2.3 (3H5m), 2.4 1 (lH, m), 2.47 (2H, m), 2.6 (4H, m), 2.80 (1H? Dd, J = 6.9, 13.7Hz) 52.92 (3H5s)? 2.93 (1 H5br.m) 53.01 (lH, dd, J = 2.9, 13.7 Hz), 3.27 (lH, t, J = 9.3HZ), 3.36 (3H, s), 3. 200414902 37 (3H, s), 3.38 (1 H, m), 3.40 (lH, m), 3.53 (1 H, t, J = 2.4 Hz), 3.86 (1H, d, J = 8.8 Hz) 53.9 (2H, m), 3.97 (1 H, m), 4.13 (lH, m), 4.18 (2H, m), 4.96 (lH, dd, J = 2.9, 9.3 Hz), 5.11 (lH, m), 5.38 (2H, m), 5.66 (lH, d, J = 8. 3Hz), 5.90 (lH, t, J = 5.9Hz), 5.93 (lH, m), 7.82 (lH5d, J = 8.3Hz) ppm 1 0) 13 C-NMR spectrum: in the middle of the secondary diformate, The standard uses heavy dimethanine (39.5ppm) for determination of 'i3C-NMR' as shown below: 9.5 (q) 514.0 (q)? I9.0 (q)? 22.1 (t)? 23.9 (t) 524.5 (t)? 27.2 (d), 2 _ 8.7 (t), 28.9 (0). 29.0 (t), 29.1 (d), 31.3 (t), 33.3 (t), 36.4 (q), 3 7.8 (q ), 3 9.4 (t), 39.6 (t), 39.8 (t), 39.9 (t), 40.7 (t), 4 1 · 5 (〇, 5 6.5 (t), 5 8.7 (q), 60.0 (q ), 62.3 (d), 66.6 (d), 69.1 (d), 70.0 (d), 70.7 (d), 72.7 (d), 73.0 (d), 74.1 (d), 76.6 (d), 77.3 (d ), 77.6 (d), 82.0 (d), 84.0 (d), 87.4 (d), 90.4 (d), 101.3 (d), 106.8 (d) 5 1 40.5 (d), 1 5 0.2 (s), 163.3 (s), 168.5 (s). 169.3 (s) 5 170 · l (s), 170.6 (s) 517 1.1 (s) 5171.8 (s)? 173.5 (s) ppm 1 1) High-speed liquid chromatography : Φ column: CAPCELLPAK C18UG120, 4.6px 150mm (made by Shiseido Co., Ltd.) Solvent: 40% acetonitrile aqueous solution containing 10mM ammonium bicarbonate Flow rate: 1.0 m 1 / min Detection: UV absorption 2 6 0 nm Holding time : 9.8 minutes 3 1 · —A kind of compound or #salt with the following physical and chemical properties, -91- 200414902 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethyl sulfoxide, and insoluble in chloroform 3) Molecular formula: C55H85N5 02 3 4) Molecular weight: 1183 (determined by FAB mass spectrometry) 5) Precision mass determined by high decomposition energy FAB mass spectrometry, [M + H] + as shown below: Measured 値: 1 1 84.5 723 Calculated 値: 1 1 8 4 · 5 7 1 4 6) Ultraviolet absorption spectrum: _ Determine the ultraviolet light absorption spectrum in methanol, and the maximum absorption is shown as follows: 263nm (ε 8100) 7) Optical rotation: Determine the optical rotation in methanol, as shown below The display shows: [a] D29: +6.5 ° (c0.2) 8) Infrared absorption spectrum: The infrared absorption spectrum measured by the potassium bromide (KBr) tablet method is expressed by the maximum absorption shown below: φ 3403, 2927,2855, 1 738,1690,1631,1466,1385,1273, il62 1 1 04,1 0 1 5,962cm-1 WH-NMR spectrum: Heavy dimethanine, internal standard uses heavy dimethene (2.49Ppm), its 1Η-NMR spectrum is shown below: 0.84 (6H t), 0.9 1 (3H, d, J = 6.0 Hz), 1.2-1.3 (12H, m), 1.42 (1H m), 1.70 (lH, m), 2.0 (5H5m), 2.14 ( 2H, m), 2.26 (3H, s), 2 3 (4 200414902 H, m), 2.42 (lH, m), 2.5 (2H, m), 2.6 (4H, m), 2.80 (lH, dd, J = 6.8, 12.8 Hz), 2.9 1 (3H, s), 2.95 (lH, br.m), 3.0 1 (lH, dd, J = 2.6, l 2.8 Hz), 3.27 (lH, t, J = 9.0 Hz), 3.36 (3H, s), 3.37 (3H, s), 3.4 (2 H, m), 3.53 (1 H, m), 3.85 (1 H, d, J = 8.1 Hz), 3.9 (2H, m), 3.96 (1 H, m) 54.13 (lH, m), 4.19 (2H, m). 4.96 (lH, dd, J = 2.6, 9.4 Hz), 5. 13 (lH, m), 5.30 (1 H, dt, J = 7.3, 9.8 Hz), 5.38 (2 H, m), 5.47 (l H, dt, J = 7.3, 9.8 Hz), 5.66 (l H, d, J = 8.1 Hz), 5.90 (lH, t, J = 5.6H z), 5.93 (lH, m), 7.82 (lH, d, J = 8.1Hz) ppm 10) 13c-NMR spectrum: Determination of heavy dimethylforma (39.5ppm), shown below as its 13 C-NMR spectrum: 9.5 (q), 14.0 (q), 19.0 (q), 22.1 (t), 23.9 (t), 2 6.7 (t), 27.1 (d), 2 8.7 (t), 28.7 (t). 28.9 (t), 28.9 (t), 29.0 (t), 29.0 (t), 29.1 (t), 3 1 · 3 ( t), 3 3 · 1 (t), 36.4 (q), 37.8 (q), 3 8.2 (t), 39.8 (t), 39.9 (0, 40.2 (t), 40.7 (t), 41.5 (t) , 56.6 (t), 58.7 (q), 60.0 (q), 62.3 (d), 66.5 (d), 69.1 (d), 69.8 (d), 70.7 (d), 72.7 (d ), 73.0 ((!), 74.1 (d), 7 6.6 (d), 77.3 (d), 77.5 (d), 82.0 (d), 84.0 (d), 87.4 (d), 90.5 ( d), ® 1 01.3 (d), 1 06.8 (d), 123.6 (d), 133.1 (d), 140.5 (d), 150.2 (s), 163.3 (s), 168.6 (s), 169.3 ( s), 170.2 (s), 170.6 (s), 171.0 (s), 171.8 (s), 173.5 (s) ppm 1 1) High-speed liquid chromatography analysis method: column: c APCELLPAK C18UG120, 4.6 φ X 1 50mm (Made by Shiseido Co., Ltd.) -93- 200414902 Solvent: 40% acetonitrile aqueous solution containing 10 mM ammonium bicarbonate. Flow rate: 1.0 ml / min. Detection: UV absorption at 260 nm. Hold time: 10.9 min. 3 2.-Has the following physical and chemical properties The compound or its salt, 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethyl sulfoxide, and insoluble in chloroform 3) Molecular formula: C57H87N5 02 3 4) Molecular weight: 1 209 (as FAB Mass spectrometry) 5) FAB [M + H] + for the precise mass measured by spectrometry is as follows: Measured 値: 1 2 1 0 · 5 8 6 7 Calculated 値: 1210.5870 6) Ultraviolet absorption spectrum: Determine the ultraviolet light absorption spectrum in methanol, as shown below The maximum absorption indicates: 263nm (ε 9900) 7) Optical rotation: The optical rotation is measured in methanol as shown below: [a] D29: +13.2 ° (c0.2) 8) Infrared absorption spectrum: As bromine The infrared absorption spectrum measured by the potassium chloride (KBr) tablet method is expressed by the maximum absorption shown below. 3383,295 7,2930,1738,1695,1629,1464,1 384,1273,1 161, 200414902 1 104, 1014,960cm · 1 9) Nuclear Magnetic Resonance Spectroscopy: In heavy dimethanine, the internal standard is measured using heavy dimethanine (2.49ppm), and its 1Η-NMR spectrum is shown below: 0.84 (6H, t ), 0.9 1 (3H, d, J = 6.0 Hz), 1.2-1.3 (8H, m), 1.42 (lH, m), 1.57 (2H, m), 1.70 (lH, m), 2.0 (7H, m ), 2.11 (lH, m), 2.17 (lH, m), 2.26 (3H, s), 2.3 (3H, m), 2.4 (3H, m), 2.5-2.6 (4H, m), 2.7 1 (2H5dd , J = 6.0 Hz), 2.80 (lH, dd, J = 7.0, 12.8 Hz), 2.9 1 ( 3 H, s), 2.93 (lH, br.m), 2.98 (lH, dd, J = 2.7, 12.8 Hz), 3.26 (lH, t, J = 9.2 Hz), 3.36 (3H, s), 3.37 ( 3H, s), 3.4 (2H, m), 3.52 (lH, m), 3.84 (lH, d, J = 8.1Hz), 3.9 (2H, m), 3.94 (lH, m), 4.14 (lH, m ), 4.2 (2H, m), 4.96 (lH, dd, J = 2.9, 9.5 Hz), 5.12 (lH, m), 5.30 (4H, m), 5.37 (2H, m), 5.66 (lH, d, J = 8.1 Hz), 5.90 (lH, t, J = 5.9 Hz), 5.93 (lH, m), 7.82 (lH, d, J = 8.1 Hz) ppm 10) 13c-NMR spectrum: heavy dimethanine The internal standard was determined using heavy dimethanine (39.5ppm) as shown below-its NMR spectrum: 9.4 (q), l 3.9 (q), i9.0 (q), 22.0 (t), 23.9 (t), 24.6 (t), 25.2 (t) 52 6.3 (t), 26.6 (t), 27.1 (d), 28.7 (t), 29.3 (t), 29.4 (t), 30.9 (t), 3 2.9 (t), 36.4 (q), 37.8 (q), 38.8 (t), 39.8 (t), 39.9 (t), 40.2 (t), 40.7 (0, 4 1.5 (t), 5 6.6 (t), 5 8.7 (q), 60.0 (q), 62.3 (d), 66.7 (d), 6 9.0 (d), 69.9 (d), 70.6 (d), 7 2.7 (d), 73.1 (d), 74.1 (d), 76.6 (d). 77.3 (d), 7 7.4 (d), 82.2 (d), 83.9 (d), 87.5 (d), 90.5 (d), 101.3 (d ), 106.7 (d ), 127.6 (d), 128.2 (d), 129.2 (d), 129.8 (d), 140.5 -95- 200414902 (d), 150.3 (s), 163.3 (s), 168.6 (s), 169.2 (s) , 170.1 (s), 170.8 (s)? 171.1 (s)? 171.9 (s)? 173.8 (s) ppm 1 1) High-speed liquid chromatography analysis method: column ·· CAPCELLPAK C18UG120, 4.6px 150mm (Shiseido Co., Ltd.) Solvent: 40% acetonitrile aqueous solution containing 10 mM ammonium bicarbonate. Flow rate: 1.0 ml / min. Detection: UV absorption at 260 nm. Holding time: 14.8 min. 3 3 Compounds or salts thereof having the following physical and chemical properties. : 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethyl arylene, insoluble in chloroform 3) Molecular formula: C55H87N50 2 3 4) Molecular weight: 1185 (determined by FAB mass spectrometry) 5) The precise mass measured by high resolution energy FAB mass spectrometry, [Μ + ΗΓ is expressed as follows: Measured 値: 1 1 8 6 · 5 8 2 8 ^ Calculated 値: 1 1 8 6 · 5 8 7 0 6) Ultraviolet absorption spectrum z The ultraviolet absorption spectrum is measured in methanol, and the maximum absorption is shown as follows: 263nm (£ 11000) 7) Optical rotation: The optical rotation is measured in methanol. The following 値 means: -96- 200414902 [α] D ”: +; i3.9 ° (c0.2) 8) Infrared absorption spectrum: Infrared absorption spectrum measured by potassium bromide (KB I ·) tablet method It is expressed by the maximum absorption shown below: 3393,2953,2927,1 738,1695,1632,1466,1 384,1273,1 162, 1 1 04,1 0 1 4,960cm · 1 9) 4-Nuclear magnetic resonance spectrum : In heavy dimethanine mill, the internal standard is determined by heavy dimethanine (2.49ppm), which is shown below as its 1 光谱 -NMR spectrum ... 0.83 (6H, t, J = 6.6Hz), 0.84 (3H , t, J = 7.3 Hz), 0.92 (3H, d, J = 6.2 Hz), 1.12 (2H, dt, J = 6.6 Hz), 1, 2-1.3 (12H, m), 1.4-1.5 (2H, m), 1.55 (2H, m), 1.70 (lH, m), 2.0 (3H, m), 2.11 (lH, m), 2.17 (lH, m), 2.26 (3H, s), 2.3 (3H, m ), 2.4-2.5 (3H, m), 2.5-2.6 (3H, m), 2.7 9 (1 H, dd, J = 6.6, 12.8 Hz), 2.9 1 (3H, s), 2.94 (l H, bi * .m) 52.9 9 (lH, dd, J = 2.8, 12.8 Hz) 53.27 (lH, t, J = 9.3 Hz), 3.36 (3H, s), 3. 37 (3H, s), 3, 40 ( 2H, m), 3.52 (lH, m), 3.84 (lH, d, J = 8.8 Hz), 3. 87 (2H, ni) 53.94 (lH, m), 4.13 (lH, m), 4.19 ( 2H, m), 4.96 (lH5d · d, J = 2.9, 9.2Hz), 5.11 (lH, m), 5.3 7 (2H, m), 5.37 (2H, m), 5.66 (lH, d, J = 8.1 Hz), 5.90 (lH, t, J = 5.5 Hz), 5.93 (lH, m), 7.83 (lH, d, J = 8. lHz) ppm i 〇) 13 c-NMR spectrum: heavy dimethanine In the internal standard, the measurement was performed using heavy dimethyfene (39.5ppm) 'as shown below-its nuclear magnetic resonance spectrum: 9 * 5 (q)? 19.〇 (q) 922.5 (q)) 23.9 (t)? 24.5 (t), 26.8 (t) 527.1 (d)? 2 -97- 200414902 7.4 (d) 528.7 (t), 28.9 (d), 28.9 (d), 29.3 (t), 29.3 (t), 29.5 (t ), 3 3.2 (t), 36.4 (q), 3 7.8 (q), 3 8.5 (t), 3 8.8 (t), 39.8 (t), 39.9 (t), 40. 1 (t), 40.2 ( t), 4 1.5 (t), 56.6 (t), 5 8.7 (q) 560.0 (q) 562.3 (d), 67.3 (d), 69.1 (d), 70.0 (d), 70.6 (d), 72.7 (d), 73.1 (d), 74.1 (d), 76.6 (d), 77.2 (d), 77.5 (d), 82.2 (d), 83.9 (d), 87.6 (d), 90.5 (d), 10 1.3 (d), 106.6 (d), 140.5 (d), 150.3 (s), 163.3 (s), 168.5 (s), 169.3 ( s), 170.1 (s), 170.8 (s), 171 · l (s), 172.0 (s), 173.8 (s) ppm 11) High-speed liquid chromatography analysis method: Column: CAPCELLPAK C18UG120, 4.6 φ X 1 50mxn ( (Made by Shiseido Lu Co., Ltd.) Solvent: 42% acetonitrile aqueous solution containing 10 mM ammonium bicarbonate. Flow rate: 1.0 ml / min. Detection: UV absorption at 260 nm. Hold time: 9.5 minutes. 34. A compound having the following physical and chemical properties or its Salt: 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethylarene®, insoluble in chloroform 3) Molecular formula: C56H87N5023 4) Molecular weight: 1197 (determined by FAB mass spectrometry) 5) [M + H] + as shown in the precise mass measured by high resolution FAB mass spectrometry: Measured radon: 1 1 9 8.5 8 7 5 Calculated radon: 1 1 9 8.5 8 7 0 6) Ultraviolet absorption spectrum: -98- 200414902 The ultraviolet light absorption spectrum is measured in methanol, and the maximum absorption is shown as follows: 2 6 3 nm (ε 8 7 0 0) 7) Optical rotation: The optical rotation is measured in methanol, as shown below: [a] D29: — 6.8 (c 0.2) 8) Infrared absorption spectrum = The infrared absorption spectrum measured by the potassium bromide (KBr) tablet method is expressed by the maximum absorption shown below: 3414, 2928, 2856, 1738, 1689, 1632, 1465,1394,1273,1 161, 1 1 26,1 1 04,1 0 1 4,959cm · 1 P) 1: »-Nuclear magnetic resonance spectrum: Among heavy dimethyl submills, the internal standard was measured using heavy dimethyl submills (2.49ppm), which is shown below as 1Η -Nuclear magnetic resonance spectrum: 0.84 (6H, t), 0.92 (3H, d, J = 6.2Hz), 1, 2-1.3 (12H, m), 1.42 (lH, m), 1.57 (2H5m), 1.71 (lH , Ni), 2.0 (7H, m), 2.11 (1 H, m), 2.17 (1 H, m), 2.25 (3H, s), 2.3 (3H, m), 2.4 1 (lH, m), 2.43 (2H, m), 2.6 (4H, m), 2.80 (1 H, dd, J = 6.6, 13.6 Hz), 2.91 (3H, s), 2.93 (lH, m), 2.98 (1 H, dd, 3.3 , 13.6Ηζ), 3.27 (lH, t, J = 9.5 Hz), 3.36 (3H, s), 3.37 (3H, s), 3.4 (2H, m) 53.52 (m, m), 3.84 (lH , D, J = 8.4 Hz), 3.87 (2H, m), 3.94 (lH, m), 4.13 (lH, m), 4.19 (2H, m), 4.96 (lH, dd, J = 3.3, 9.5 Hz) , 5.90 (lH, t, J = 5.9 Hz), 5.37 (2H, m), 5.66 (lH, d, J = 8 "Hz), 5.90 (lH, t, J = 5.9 Hz), 5.93 (lH, m ), 7.83 (lH, d, J = 8.1H z) ppm 1 0) 13 C-Nuclear magnetic resonance spectrum: -99- 200414902 In heavy dimethanine, the internal standard was determined using heavy dimethanine (39.5ppm) ' Shown below for its i3 C-NMR spectrum: 9.5 (q) 5l4.〇 (q) 5! 9.0 (q) 5 2 2. l (q), 23.9 (t), 24.8 (t), 26.3 (t) 526. 6 (q ), 27.1 (d) 528.6 (t), 28.6 (t), 29.0 (t), 29.1 (t), 29.3 (t), 3 1.3 (t), 32.9 (t), 36.4 (q), 37.8 (q ), 38.9 (t), 39.8 (t), 39.9 (t), 40.2 (t), 40.7 (t), 4 1.5 (t), 56.6 (t), 5 8.7 (q), 60.0 (q) , 62.3 (d), 66.7 (d), 69.0 (d), 69.9 (d), 70.5 (d), 72.7 (d), 73.2 (d), 74.1 (d), 76.6 (d), 7 7.2 (d), 77.5 (d), 82.2 (d), 83.9 (d), 89.1 (d), 90.5 (d), 10 1.3 (d), 106.6 (d), 129.1 (d), 130.1 (d), 140.6 (d), 150.3 (s), 163. φ 3 (s), 168.4 (s), 169.2 (s), 170.1 (s), 170.8 (s), 171.1 (s), 172.0 (s), 173.8 ( s) ppm 1 1) High-speed liquid chromatography analysis method: Column: CAPCELLPAK C18UG120, 4.6 φ X 1 50mm (made by Shiseido Co., Ltd.) Solvent: 42% acetonitrile aqueous solution containing 10 mM ammonium bicarbonate Flow rate: 1.0 ml / min Inspection Out: UV absorption 2 6 0 nm _ Holding time: 10.2 minutes 3 5 · — A compound or a salt thereof having the following physical and chemical properties: 1) Properties of the substance: colorless powdery substance 2) Solubility Soluble in methanol and dimethyl arylene, insoluble in chloroform. 3) Molecular formula: C55H87N5023 4) Molecular weight: 1185 (determined by FAB mass spectrometry) 5) Precision mass determined by high decomposition energy FAB mass spectrometry, [m + h] + as follows The column -100- 200414902 indicates: Measured radon: 1 1 8 6 · 5 9 1 2 Calculated radon: 1 1 8 6 · 5 8 7 0 6) Ultraviolet absorption spectrum: Measured in methanol. Determine the ultraviolet absorption spectrum, as shown below The maximum absorption indicates: 263nm (ε 3600) 7) Optical rotation: The optical rotation is measured in methanol, and it is expressed as follows: Lu [a] D29: + 4.3. (C0.5) 8) Infrared absorption spectrum: The infrared absorption spectrum measured by the potassium bromide (KBr) lozenge method is expressed by the maximum absorption shown below: 3371, 2926, 2855, 1738, 1691, 1628, 1466, 1 384,1273,1 161, 1 1 04,1 0 1 6,962cm * 1 9) Plutonium-NMR spectrum: In heavy dimethanine, the internal standard uses heavy dimethanine (2.05ppm). Shown as its iH-NMR spectrum: 0.84 (6H, t), 0.92 (3H, d, J = 5.5Hz), 1.2-1.3 (18H, m), 1.42 (lH, m), 1.55 ( 2H, m), 1.70 (lH, m), 2.0 (3H, m), 2.14 (2H, m), 2.26 (3H, s), 2.3 (3H, m), 2.41 (lH, m), 2.47 (2 H, m), 2.6 (4H, m), 2.80 (lH, dd, J = 6.2, 13.6 Hz), 2.92 (3H, s), 2.94 (lH? Br.m) 53.01 (lH.dd5J = 2.2 13.6 Hz) 53.27 (lH5t5J = 8.8 H2), 3.30 (3H, 5), 3.37 (3H55), 3.40 (2H, m), 3.53 (lH, m), 3.8 -101- 200414902 6 (lH, d, J = 9.5 Hz), 3.9 (3H, mM. 13 (lH, m), 4.19 (2H, m), 4.96 (lH, dd, J = 1.8, 9.2 Hz), 5.11 (lH, m), 5.37 (2H M), 5.65 (lH, d, J = 7.7Hz)? 5.90 (lH? T? J = 5.0Hz)? 5.93 (lH, m)? 7.81 (lH? D? J = 7. 7 H z) ppm1 0) 13 c-Nuclear magnetic resonance spectrum: In heavy dimethanine, the internal standard was determined using heavy dimethanine (39.5ppm), and its 13C-nuclear magnetic resonance spectrum is shown below: 9.5 (q), 14.0 (q ), 19.0 (q), 22.1 (t), 23.9 (t), 24.5 (t), 27.2 (d), 28.7 (t), 28.7 (0), 28.9 (t), 28.9 (t), 29.0 (t ), 29.0 (t), 29.1 (d). 3 1.3 (t), 33.3 (t), 36.4 (q), 37.8 (q), 3 8.8 (t), 39.8 (t), 39.9 (t), 40.2 (t), 40.7 (t), 4 1.5 (t), 5 6.S (t), 5 8.7 (q), 60.0 (q), 62.4 (d), 66.5 (d), 69.0 (d), 70.6 (d), 72.7 (d), 72.9 (d), 74.1 (d), 76.6 (d), 77.3 (d), 77.5 (d), 82.0 (d), 84.0 (d), 87.3 (d) , 90.4 (d), 101.3 (d), 106.9 (d), 140.5 (d), 150.2 (s), 163.3 (s), 168.7 (s), 169.3 (s), 170.1 (s), 170.6 (s ), 171.1 (s), 171.8 (s), 173.5 (s) ppm 1 1) High-speed liquid chromatography: column: C APCELLPAK C18UG120, 4.6 ¢) x 1 50mm (made by Shiseido Co., Ltd.) solvent: containing 10mM ammonium bicarbonate in 42% acetonitrile solution. Flow rate: 1.0ml / min. Detection: UV absorption at 260nm. Hold time: 1 1.2 minutes. 3. 6. Kinds of the following physical and chemical properties Compound or its salt, -102- 200414902 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in water, insoluble in chloroform 3) Molecular formula: 4) Molecular weight: 543 (determined by FAB mass spectrometry) 5 ) Accurate mass measured by high resolution FAB mass spectrometry, [M + ΗΓ is expressed as follows: Measured 値: 5 4 4.2 2 4 0 Calculated 値: 544.2255 6) Ultraviolet absorption spectrum: _ Measure the ultraviolet light absorption spectrum in water, as shown below The maximum absorption indicates: 2 6 3 nm (ε 8 70 0) 7) Optical rotation: Measure the optical rotation in water, as shown below: [a] D2 9: + 6 2.7 ° (c0.2) 8) Infrared absorption spectrum z is expressed by the maximum absorption shown in the following column as determined by the potassium bromide (KB 〇 tablet method) infrared absorption spectrum: 3393,2929,1688,1620.1468,1394,1274.1094,1065,1019, 9 6 2 cm ~ 1 9) 1 NMR spectrum: In heavy water, the internal standard is measured using heavy water (4.75 ppm), and its 1H-NMR spectrum is shown below: 2.2 1 (lH, ddd, J = 3.3, 5.9, 14.7 Hz), 2.3- -103- 200414902 2.4 (3H, m), 2.44 (3H, s), 2.86 (lH, dd, J = 9.2, 13.6 Hz), 2.97 (lH, d, J = 14.7 Hz), 3.07 (3H, s), 3.13 (lH, d, J = 14.7 Hz), 3.24 (1 H, dd, J = 4.4, l 3.6 Hz), 3.80 (lH, d, J = 9.9 Hz), 3.93 (1 H, d, J = 6.6 Hz), 4.20 (lH, d, J = 5 · 1Ηζ), 4.25 (lH, dt , J = 7.0 Hz), 4.38 (1 H, m), 4.4 1 (lH, d, J = 9.9 Hz), 4.44 (lH, m), 5.56 (lH, dd, J = 3.3, 5 · 9Ηζ), 5.8 l (lH, d, J = 8.1 Hz), 6.00 (lH, t, J = 5.5 Hz), 7.74 (1 H, d, J = 8.1 Hz) ppm 10) 13c-NMR spectrum: heavy water The internal standard was determined using dioxane (66.5PPm), and its NMR spectrum is shown below: 36.4 (q), 38.6 (q), 38.7 (t), 40.1 (t), 40.4 (t), 58.6 ( t), 63.1 (d), 6 8.7 (d), 69.1 (d), 69.4 (d), 7 1.8 (d), 76.9 (d), 8 1.6 (d), 85.0 (d), 85.3 ( d), 101.3 (d), 109.0 (d), 142.2 (d), 15 1.4 (5), 166.5 (5), 1 7 2.3 (5), 1 7 3.5 (5) ppm 11) High-speed liquid color Layer analysis method: Column: CAPCELLPAK C18UG120, 4.60 X 1 50mm (manufactured by Shiseido Co., Ltd.) Solvent: 10 mM ammonium bicarbonate Flow rate: 1.0 mm / min Detection: UV absorption 260 nm Hold time 9 · 2 minutes 3 7 · —A kind of compound or its salt with the following physical and chemical properties: 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethyl arylene, and insoluble in chloroform-104 -200414902 3) Molecular formula: C22H31N5O10 4) Molecular weight: 5 2 5 (determined by FAB mass spectrometry) 5) Precision mass determined by high decomposition energy FAB mass spectrometry, [M + H] + as shown below: Actual measurement: 5 2 6.2 1 5 3 Calculate 値: 526.9149 6) Ultraviolet absorption spectrum: Measure the ultraviolet absorption spectrum in water, and the maximum absorption is shown below. 260nm (£ 8700) 7) Optical rotation: Measure the optical rotation in water, as shown below: Means: [a] D2 9: + 6 5.5. (C0.2) 8) Infrared absorption spectrum: The infrared absorption spectrum measured by the potassium bromide (KBr) lozenge method is expressed by the maximum absorption shown below: 3403, 2953, 1 690, 1633, 1467, 1382, 1361, 1 274, 1098, 1067, 1 0 1 3.9 64cm'1 9) iH-NMR spectrum: In heavy water, the internal standard is measured using heavy water (4.7 5PPm). The 1H-NMR spectrum is shown below: 2.2- 2 · 4 (4Η, m), 2.43 (3Η, s), 2.86 (1 H, dd, J = 9.9, 13.6 Hz), 2.92 (1 H, dd, J = 6.6, 12.7 Hz), 2.97 (3H, s), 3.23 (lH, dd, J = 4.0, i36-105 · 200414902 Hz) 53.3 2 (lH, dd, J = 7.3, 12 · 7Ηζ), 3.87 (1 H, d, J = 9.5 Hz), 4.0 8 (lH, m), 4.18 (lH, m), 4.3 1 (lH, dt, J = 5.8 Hz), 4.35 (lH, m), 4. 38 (lH, m), 5.56 (lH, dd, J = 2.6, 5.9 Hz), 5.80 (lH, d, J = 8.1 Hz), 6.06 (1 H, t, J = 5.9 Hz), 6.47 (1 H, dd, J = 6 · 6, 7.3 Hz), 7.64 (l H, d, J = 8.1 Hz) ppm 10) 13 C-Nuclear magnetic resonance spectrum: In heavy water, the internal standard was measured using dioxane (66.5PPm), and its nuclear magnetic resonance spectrum is shown below: 32.7 (q) , 38.6 (t), 40. 0 (q), 40.5 (t), 40.9 (t), 5 1.0 (t), 63.2 (d), 69.8 (d), 71.7 (d), 76.7 (d), 82.4 (d), 85.2 (d) , 85.6 (d), 101.8 (d) 5 107.7 (d), 123.1 (d), 141.4 (d), 144.2 (s), 152.4 (s), 167.7 (s), 168.6 (s), 171.0 (s) ppm 11) High-speed liquid chromatography: column: CAPCELLPAK C18UG120,4.6 < 6x 150mm (manufactured by Shiseido Co., Ltd.) Solvent: 3% acetonitrile aqueous solution containing 10% 1M ammonium bicarbonate Flow rate: 1.0ml / min Detection: UV absorption 2 60nm Holding time: 13.0 minutes 3 8 Compounds or their salts with the following physical and chemical properties, 1) Properties of the substance: colorless powdery substance 2) Solubility: soluble in methanol, dimethylene®, insoluble in chloroform 3) Molecular formula: C42H67N5016 4) Molecular weight: 897 (as FAB mass spectrometry) -106- 200414902 5) Accurate mass determined by high decomposition energy FAB mass spectrometry, [Μ + 如 Γ is expressed as follows: measured 値: 8 9 8.46 6 9 calculated 値: 89 8.466 1 6) UV absorption spectrum: The ultraviolet absorption spectrum is measured in methanol, and the maximum absorption is shown as follows: 263nm (ε 7500) 7) Optical rotation: The optical rotation is measured in methanol, as shown below: [a] d29 ·· + 19.8 ° ( c0.2) 8) Infrared absorption spectrum: $ The infrared absorption spectrum measured by the potassium bromide (KBr) lozenge method is expressed by the maximum absorption shown below: 3394, 2926, 2855, 1 737, 1 691, 1629, 1467 , 1397,12 74,12〇3 1 131,1 094,1 0 1 3,962cm-1 9) iH-NMR spectrum: In heavy dimethanine, the internal standard uses heavy dimethanine (2.49Pρη〇. Shown as ^ Η-NMR spectrum: 0.84 (3H, t, J = 7.1Hz), 0.88 (3H, d, J = 6.3Hz), 1.2- # 1.3 (18H, m), 1.57 (2H, m) , 1.9-2.2 (8H, m), 2.24 (3H, s), 2.43 (lH, dd, J = 5.5-15.1 Hz), 2.54 (lH, dd, J = 8.2, 15.4 Hz), 2.66 (lH, dd , J = 4.4, i 5.4 Hz), 2.7 4 (lH, dd, J = 6.3, 12.6 Hz), 2.91 (3H, s), 2.93 (iH m), 2.99 (lH, dd, J = 3.8, 12.6 Hz ), 3.30 (lH, m), 3.83 (lH5d, j = 9.1Hz) 53.9-4.0 (3H, m), 4.12 (lH, dt, J = 5.2, 5.5Hz), 4.2 (2H, m), 5. 〇8 (1H -107- 200414902 m) 55.38 (2H? M) 55.67 (1 H? D, J = 8.0Hz), 5.90 (1 H? T? J = 6.0Hz)? 7.8l (lH, d.〇 Hz), 5.90 (lH, t5J = 6.0Hz), 7.8 1 (lH, d, J = 8. 0) ppm 1〇) I3C_NMR spectrum ····························································································· for The internal standard as the double standard for NMR Yafeng (39.5PPm) was determined as shown below for its 13C-NMR spectrum: 14.0U), 19.4 (q), 22.1 (t), 24.6 (t), 27.1 (d), 28.7 (t), 2 8.7 (t), 28.9 (t), 29.0 (t), 3i.3 (t), 33.2 (t), 36.4 (q), 3 7.8 (q), 3 8.9 (t), 39.8 (t) , 39.9 (t), 40.1 (t), 40.4 (t), 4 1.5 (t), 5 6.6 (t), 62.3 (d) '66.6 (d), 69.1 (d), 69.9 (d), 70.7 (d), 72.8 (d), 77.6 (d), 82.0 (d), 83.9 (d), 87.4 (d), 101.3 (d), 107.0 (d), 140.5 (d), 150.2 (d), 163.3 (s), 168.5 (s), 169.3 (s), 170.7 (s), 171.5 (s), 173.8 (s) ppm 1 1) High-speed liquid chromatography analysis method: Tube column: CAPCELLPAK C18UG120, 4.64x 150mm (manufactured by Shiseido Co., Ltd.) Solvent: Contains 0.2% triethylamine-phosphate buffer solution, adjusts pH 33 to 55% acetonitrile aqueous solution. Flow rate: 1. 〇m 1 / min. Detection: UV absorption 2 60 nm retention time: 4.0 minutes 3 9 · —a compound or a salt thereof having the following physical and chemical properties, i) the properties of the substance: a colorless powdery substance 2) solubility: soluble in methanol, dimethyl arylene, Insoluble in chloroform-108- 200414902 3) Molecular formula · C54H85N5023 4) Molecular weight: U71 (determined by FAB mass spectrometry) 5) FAB quality according to high decomposition energy | Precise mass determined by common method '[M + Η] + as follows Representation: Measured radon: 1 1 72.5 7 3 1 Calculated radon: 1 1 7 2 · 5 7 1 3 6) Ultraviolet absorption spectrum: Determine the ultraviolet light absorption spectrum in methanol, and the maximum absorption expression is as follows: 263nm (ε 1 0400 ) 7) Optical rotation: Measure the optical rotation in methanol as shown below: [a] D29: + 1 0 · 6 c (c0.3) 8) Infrared absorption spectrum: Take potassium bromide (KBr) ingot The infrared absorption spectrum measured by the agent method is expressed by the maximum absorption shown below: 3403,2926,2855,1 739,1695,1628,1467,1 384,1 273,1 162, 1 103,1013,966cm'1 9) 1H-NMR spectrum: Among the heavy dimethylphosphataene, the internal standard was determined using heavy dimethyldiamine (2.49Ppm). The following is shown for its Η-NMR spectrum: 0.83 (3H.t, J = 6.6Hz), 0,9 1 (3H, d, J = 6.3Hz), 1.17 (3H, d, J = 6 0Hz), 1.2-1.3 (18H, m), 1.55 (2H, m), 1.9-2.1 (3H , M), 2,13 (2 Hm), 2.26 (3H, s), 2.3-2.4 (3H, m), 2.4 1 (lH, dd, J = 6.0, l5.4 • 109-200414902 Hz), 2.47 (2H, m), 2.6 (4H, m), 2,80 (lH, dd, J = 5.8, 12.6Hz), 2.92 (3H, s), 2.9-3.0 (2H, m), 3.20 (lH , D d, J = 9.0, 9.6 Hz), 3.32 (lH, m), 3.36 (3H, s), 3.37 (lH, m), 3.38 (3H, s), 3.41 (lH, m), 3.52 (1 H, m), 3.5 9 (lH, dq, J = 6.0, 9.0 Hz), 3.80 (lH, d, J = 8.5 Hz), 3.9 (2H, m), 3.94 (lH, d, J = 3.3 Hz), 4.10 (lH, m), 4.21 (2 H, m), 4.94 (lH, dd, J = 3.0, 9.6 Hz), 5.11 (lH, m), 5.37 (2H, m) 5 5.66 (1 H, d, J = 8.0Hz), 5.89 (lH, t, J = 5.5Hz), 5.90 (lH, d, J = 1, 4Hz), 7.8 1 (lH, d, J = 8.0Hz) ppm 10) 13c-NMR spectrum : In heavy dimethanine, the internal standard was determined using dimethanine (39.5ppm), and its 13C-NMR spectrum is shown below: 1 4.0 (q), 17.7 (q), 19.0 (q), 22. l (t), 24.6 (t), 27.1 (t), 28.7 (t), 28.7 (t), 28.9 (t), 29.0 (t), 29.1 (t), 3 1.3 (t), 3 3.3 (t), 36.3 (q), 37.8 (q), 3 8.8 (t), 39.8 (t). 39.9 (t), 40.0 (t), 40.2 (t), 4 1.4 (t), 56.6 (t) , 5 8.7 (q), 60.2 (q), 62.4 (d), 66.4 (d), 69.0 (d), 69.6 (d), 70.0 (d), 70.5 (d), 72.5 (d), 72.8 (d), 76.7 (d), 77.4 (d), 79.2 (d), 82.0 (d), 84.0 (d), 87.2 (d), 90.4 (d), 101.2 (d), 107.0 (d) , 140.4 (d), 150.2 (5), 163.3 (5), 169.0 (5), 169.3 (5), 17 0.2 (5). 170.7 (5), 171.2 (5), 171.8 (5), 1 73.5 (5) ppm 11) High speed Liquid chromatography analysis method: Column: CAPCELLPAK C18UG120, 4.6 φ X 1 50mm (made by Shiseido Co., Ltd.) Solvent: Contains 0.2% triethylamine-phosphate buffer solution, and adjusts pH 5 · 5% of 5% acetonitrile aqueous solution-110 -200414902 Flow rate: 1.0ml / min Detection: UV absorption at 260nm Hold time: 6.5 minutes 40 ° —A kind of compound or its salt with the following physical and chemical properties, 1) Properties of the substance: colorless powdery substance 2) Solubility : Soluble in methanol and dimethyl sulfoxide, insoluble in chloroform 3) Molecular formula: C54H85N5 02 3 4) Molecular weight: 1171 (determined by FAB mass spectrometry) 5) Precision mass determined by high decomposition energy FAB mass spectrometry, [M + H ] + As shown below: Measured 値: 1 1 7 2.5 7 3 1 Calculated 値: 1 1 7 2.5 7 1 3 6) Ultraviolet absorption spectrum: Determine the ultraviolet absorption spectrum in methanol, and the maximum absorption expression is as follows: 262nm ( ε 11000) 7) Optical rotation: Measure the optical rotation in methanol as shown below: [a ] D29: + 14.2 ° (c0.2) 8) Infrared absorption spectrum: The infrared absorption spectrum measured by the potassium bromide (KBr) lozenge method is expressed by the maximum absorption shown in the τ column: 3368, 2927, 2856, 1735, 1707,1674,1 65 1,161 5,1466,1378 1 276,1 1 6 1,1 1 04,95 1 cm · 1 -111- 200414902 9) 1Η-Nuclear magnetic resonance spectrum: in heavy methanol, internal standard used The measurement of heavy methanol (4.7 8 ppm) is shown below as its iH-NMR spectrum: 0.76 (3H, t, J = 7.0 Hz), 0.8 1 (3H5d, J = 7.4 Hz), 0.90 (3H, d, J = 6.4Hz), 1.2-1.3 (18H, m), 1.37 (lH, ni), 1.51 (2H, m), 1.68 (lH, m), 2.1-2.2 (4H, m), 2.2-2.4 (5H , m), 2.42 (3H, s), 2.5-2.6 (6 H, m), 2.85 (lH, dd, J = 8.3, 13.4 Hz), 3.0 (2H, br, d), 3.09 (lH, dd, J = 4.0, 13.4 Hz), 3.22 (lH, dd, J = 9.0, 9.0 Hz), 3.32 (3H, s), 3.34 (3Η, s), 3.37 (1 H, m), 3.49 (1 H , Dd, J = 2.3, 3.3 Hz), 3.8 (1 H, br, d), 4.0 (2H, m), 4.10 (lH, dd, J = 6.0, 6.4 Hz), 4.2 (2H, m), 4 · 26 (1 H, dd, J = 2.0,8 · 7Ηζ), 4.96 (lH, dd, J = 3.3,9.0Hz), 5.1 4 (1H, m), 5.2-5.4 ( 1H, br m), 5.41 (lH, t, J = 4.9Hz), 5.94 (1 H, t, J = 5.0Hz), 7.71 (lH, d, J = 8.0Hz) ppm 10) 13c-NMR spectrum : In heavy dimethanine, the internal standard is determined using heavy methanol (49.0ppm), and its 13C-NMR spectrum is shown below: 1 0 · 1 (q), 1 4.5 (q), 20 · l (q) , 23.8 (t), 25.6 (t), 26.3 (t), 28.9 (d), 29.8 (t), 30.3 (t), 30.4 (t), 30.5 (t), 30.6 (t), 3 0.7 (t ), 30.8 (t), 3 3.9 (t), 3 5.3 (t), 37.0 (q), 40.7 (t), 40.8 (t) 541.2 (t), 4 1.5 (t), 58.4 (t), 59.7 (q), 61.0 (q), 62.6 (d), 66.3 (d), 68.8 (d), 69.4 (d), 69.7 (d), 72.0 (d), 72.9 (d), 73.0 (d), 74.8 (d), 76.2 (d), 78.6 (d), 79.3 (d), 84.2 (d), 86.6 (d), 87.1 (d), 92.4 (d), 103.3 (d), 109.1 (d), 144.3 (d), 141.9 (s), 164.4 (s), 165.8 (s), 170.1 (s), l 71.0 (s), 172.2 (s), 173.6 (s), 175.9 (s) ppm • 112 · 200414902 11) High-speed liquid chromatography analysis method: Eyepiece · CAPCELLPAK C18UG12O, 4.60x 150mm (made by Shiseido Co., Ltd.) Solvent: Contain 0.2% triethylamine-phosphate buffer solution, pH 3.3 and 55% acetonitrile aqueous solution Flow rate: 1 · 0 m 1 / min Detection: UV absorption at 260nm Hold time: 7.0 minutes 4 1. A method for manufacturing a compound according to any one of the claims 1 to 40 in the patent application scope ', characterized in that the culture belongs to Alternaria Production of a compound of any one of the compounds in the scope of patent application No. 1 to 40 for the production of cysts (Streptosp or an gi um) The compound of any one of the scope of patent applications No. 1 to 40 is collected from the culture . 42. The manufacturing method according to item 41 of the application, wherein the culturing is performed in a fatty acid-containing medium. 43. The manufacturing method according to item 42 of the scope of patent application, wherein the fatty acid is a linear saturated fatty acid having 10 to 20 carbon atoms. 44. The manufacturing method according to item 42 of the patent application, wherein the fatty acid is a linear saturated fatty acid having 12 to 18 carbon atoms. 4 5 · The manufacturing method according to any one of items 41 to 44 in the scope of patent application, wherein the compound belonging to Streptosporangium (Streptosporangium) is a compound in any one of the scope of application patents 1 to 40 The producing strain was Streptosporangium sp. S AN K6 0 5 0 1 (FE RM BP-7 9 8 4). 46 · —A micro-biology 200414902 of any one of the compounds in the application scope of the patent application No. 1 to 40, which belongs to Streptosporangium sp. 47 · —Streptosporangium sp. SANK 6501 (FERM BP-7984). 4 8. — A method for manufacturing a compound in the scope of patent application No. 25 or 36, which hydrolyzes the compound in any one of the scope of patent application Nos. 1 to 19, 2 9 to 3 5 and 3 8 to 39 Or restore. 49. A method for manufacturing a compound in the scope of patent application No. 26 or 37, which is to hydrolyze or reduce a compound in any one of the scope of patent applications 1 to 19, 29 to 35, and 38 to 39. 50. A method for manufacturing the 27th compound in the scope of patent application, which is to hydrolyze or reduce the compound in any one of the 20th to 24th and 40th scope of the patent application. 5 1 · A method for manufacturing the 28th compound in the scope of patent application, which is to hydrolyze or reduce the compound in any one of the patent scopes 20 to 24 and 40. 5 2 · A medical music composition containing a compound or a pharmacologically acceptable salt thereof as an active ingredient in any one of the patent application scopes 1-4 to 40. 53. The pharmaceutical composition according to item 53 of the scope of patent application, which is an antibacterial agent. 54. A method for treating a bacterial infection, comprising administering an effective amount of a compound of any one of claims 1 to 40 or a pharmacologically acceptable salt thereof to a patient. 5 5—The use of the compound of any one of items 2 to 40 in the scope of patent application or its pharmacologically acceptable salt, which is used for the manufacture of antibacterial agents.
TW092132490A 2002-11-20 2003-11-20 Novel antibiotic compound, muraminomicin TW200414902A (en)

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