JP2809573B2 - New lysophosphatidylinositol and its production method - Google Patents
New lysophosphatidylinositol and its production methodInfo
- Publication number
- JP2809573B2 JP2809573B2 JP4640993A JP4640993A JP2809573B2 JP 2809573 B2 JP2809573 B2 JP 2809573B2 JP 4640993 A JP4640993 A JP 4640993A JP 4640993 A JP4640993 A JP 4640993A JP 2809573 B2 JP2809573 B2 JP 2809573B2
- Authority
- JP
- Japan
- Prior art keywords
- lysophosphatidylinositol
- present
- new
- production method
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Agricultural Chemicals And Associated Chemicals (AREA)
Description
【０００１】[0001]
【産業上の利用分野】本発明は、抗カビ性を有する新規
リゾホスファチジルイノシトール及びその製造法に関す
る。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel lysophosphatidylinositol having antifungal properties and a method for producing the same.
【０００２】[0002]
【従来の技術】マボヤ(Halocynthia roretzi) は、東北
地方で食用として養殖されているが、被嚢 (特に出入水
管部分) には、他の生物が付着しにくいことが次のこと
から予見される。仮に、他の生物が出入水管部分を塞ぐ
と、マボヤは、海水とともに餌を吸入することも、***
することも不可能となり、死に至る。2. Description of the Related Art Maboya (Halocynthia roretzi) is cultivated for food in the Tohoku region, but it is anticipated that other organisms are unlikely to adhere to the capsule (especially the irrigation and drainage pipes) from the following. . If other organisms block the water pipe, maboya will not be able to inhale or excrete food with seawater, and will die.
【０００３】[0003]
【発明が解決しようとする課題】本発明者らは、マボヤ
出入水管部分には他の生物の幼生の付着・生育を阻害す
るような化学物質が存在することを予想し、抗カビ性を
指標として精製を行った。その結果、新規リゾホスファ
チジルイノシトールを単離し、構造を決定することに成
功した。DISCLOSURE OF THE INVENTION The present inventors have anticipated that a chemical substance that inhibits the attachment and growth of larvae of other organisms will be present in the water pipes of the maboya, and indicates the antifungal property as an index. For purification. As a result, the novel lysophosphatidylinositol was isolated and its structure was determined.
【０００４】[0004]
【課題を解決するための手段】本発明のリゾホスファチ
ジルイノシトールは、次式（Ｉ）：The lysophosphatidylinositol of the present invention has the following formula (I):
【０００５】[0005]
【化２】 Embedded image
【０００６】で示されるものである。本発明のリゾホス
ファチジルイノシトールは、グリセロールの１級の水酸
基にエイコサペンタエン酸がエステル結合した化合物で
ある。本発明のリゾホスファチジルイノシトールは、マ
ボヤ(Halocynthia roretzi)の被嚢より抽出・精製する
ことにより得ることができる。[0006] The lysophosphatidylinositol of the present invention is a compound in which eicosapentaenoic acid is ester-linked to a primary hydroxyl group of glycerol. The lysophosphatidylinositol of the present invention can be obtained by extracting and purifying from bursa of Halocynthia roretzi.
【０００７】ここで用いる抽出溶媒としては、一般には
有機溶媒、好ましくはエタノール、メタノール、アセト
ン、プロパノール等の水混和性溶媒及び水が挙げられ
る。得られた抽出液は、好ましくは、濃縮後、水層をエ
ーテル、酢酸エチル、クロロホルム等の水と混和しない
有機溶媒で抽出し、次いで、得られる水層を精製するこ
とにより目的とするリゾホスファチジルイノシトールを
効率よく得ることができる。The extraction solvent used here generally includes an organic solvent, preferably a water-miscible solvent such as ethanol, methanol, acetone and propanol, and water. The resulting extract is preferably concentrated, and then the aqueous layer is extracted with an organic solvent immiscible with water such as ether, ethyl acetate and chloroform, and then the resulting lysophosphatidyl is purified by purifying the resulting aqueous layer. Inositol can be obtained efficiently.
【０００８】精製は、シリカゲルクロマトグラフィー、
逆相シリカゲルクロマトグラフィー、逆相高速液体クロ
マトグラフィー等を適宜組み合わせることにより行うこ
とができる。以上のようにして得られる本発明のリゾホ
スファチジルイノシトールは抗カビ性を有し、抗カビ剤
として有用である。[0008] Purification is performed by silica gel chromatography,
It can be carried out by appropriately combining reverse phase silica gel chromatography, reverse phase high performance liquid chromatography and the like. The lysophosphatidylinositol of the present invention obtained as described above has an antifungal property and is useful as an antifungal agent.
【０００９】[0009]
【実施例】以下、実施例により本発明を更に具体的に説
明するが、本発明の範囲は、かかる実施例に限定される
ものではない。 （実施例１） （１）単離操作 青森県浅虫で養殖されたマボヤの被嚢のうち出入水管部
分２kgを70％エタノール１L で３回抽出し、濃縮後の水
層をエーテル 0.5L で３回抽出して得られた水層をｎ−
ブタノール 0.5L で３回更に抽出した。EXAMPLES The present invention will be described more specifically with reference to the following examples, but the scope of the present invention is not limited to these examples. (Example 1) (1) Isolation operation Of the bursa of maboya cultivated in Asamushi, Aomori Prefecture, 2 kg of the irrigation and drainage pipes were extracted three times with 1 L of 70% ethanol, and the concentrated aqueous layer was extracted with 0.5 L of ether. The aqueous layer obtained by multiple extractions is
The mixture was further extracted three times with 0.5 L of butanol.
【００１０】抗カビ (Mortierella ramaniana)活性を指
標として、ｎ−ブタノール層の一部（70％）の精製を以
下の手順で行った。 １) 逆相シリカゲルカラムクロマトグラフィー (メタノ
ール：水＝８：２) ２) シリカゲルカラムクロマトグラフィー(クロロホル
ム：メタノール：水＝７：４：0.5) ３) 逆相高速液体クロマトグラフィー（アセトニトリ
ル：0.01Ｎ塩化ナトリウム水溶液＝５：５) 前記式（Ｉ）で示される本発明のリゾホスファチジルイ
ノシトールの単離収量は2.0mg (1.4×10-4％) であっ
た。 （２）構造決定 本発明のリゾホスファチジルイノシトールは、高分解能
ＦＡＢマススペクトル（HRFABMS)により分子式 C29H46N
aO12Pが明らかとなった。1H 完全照射13C NMRスペクト
ルで４本の炭素シグナルが二重線［δ67.84 (J=5.7Hz)
、70.02(J=7.0Hz)、73.35(J=5.4Hz)、78.49(J=5.8H
z)］を示したが、それらの結合定数からリン酸エステル
の存在が示唆された。そこで、31P NMR スペクトルを測
定し、確証を得た。更に、２次元 NMRスペクトル等各種
スペクトルの解析により、本発明のリゾホスファチジル
イノシトールは、グリセロールの１級の水酸基にエイコ
サペンタエン酸がエステル結合したリゾホスファチジル
イノシトールであると決定された。Using the antifungal (Mortierella ramaniana) activity as an index, a part (70%) of the n-butanol layer was purified by the following procedure. 1) Reversed-phase silica gel column chromatography (methanol: water = 8: 2) 2) Silica-gel column chromatography (chloroform: methanol: water = 7: 4: 0.5) 3) Reversed-phase high-performance liquid chromatography (acetonitrile: 0.01N chloride) Aqueous sodium solution = 5: 5) The isolated yield of lysophosphatidylinositol of the present invention represented by the above formula (I) was 2.0 mg (1.4 × 10 −4 %). (2) Structure Determination The lysophosphatidylinositol of the present invention has a molecular formula of C 29 H 46 N by a high-resolution FAB mass spectrum (HRFABMS).
aO 12 P was revealed. Four carbon signals are doublets [δ67.84 (J = 5.7Hz) in the 1 H complete irradiation 13 C NMR spectrum.
, 70.02 (J = 7.0Hz), 73.35 (J = 5.4Hz), 78.49 (J = 5.8H
z)], but their binding constants suggested the presence of phosphate esters. Therefore, the 31 P NMR spectrum was measured to obtain confirmation. Further, by analysis of various spectra such as a two-dimensional NMR spectrum, it was determined that the lysophosphatidylinositol of the present invention was lysophosphatidylinositol in which eicosapentaenoic acid was ester-linked to the primary hydroxyl group of glycerol.
【００１１】本発明のリゾホスファチジルイノシトール
の物理定数は、以下の通りである。 1 H NMR(CD3OD) ： （エイコサペンタエン酸部分） δ0.96(3H, t, J=7.6Hz, 20-H3), 1.68(2H, dt, J=14.5
and 7.4Hz, 3-H2),2.08(2H, dt, J=14.5 and 7.3Hz, 1
9-H2), 2.12(2H, m, 4-H2),2.36(2H, t, J=7.5Hz, 2-
H2), 2.82(4H, m, 7 and 16-H4),2.85(4H, m, 10 and 1
3-H4),5.27-5.40(10H, m, 5, 6, 8, 9, 11, 12, 14, 1
5, 17 and 18-H10) （イノシトール部分） δ3.19(1H, t, J=9.8Hz, 5-H), 3.37(1H, dd, J=9.8 an
d 2.8Hz, 3-H),3.62(1H, t, J=9.8Hz, 4-H), 3.76(1H,
t, J=9.8Hz, 6-H),3.91(1H, ddd, J=9.8, 8.1 and 2.8H
z, 1-H), 4.20(1H, t, J=2.8Hz, 2-H) （グリセロール部分） δ3.97(3H, m, 1 and 2-H3), 4.11(1H, dd, J=11.4 and
5.9Hz, 3-H),4.17(1H, dd, J=11.4 and 4.2Hz, 3-H)13 C NMR(CD3OD)： （エイコサペンタエン酸部分） δ14.65(q, C20), 21.50(t, C19), 25.90(t, C3),26.44
and 26.56(each t, 1×C and 3×C, respectively,
C7, 10, 13 and16), 27.58(t, C4), 34.34(t, C2), 12
8.21, 128.95, 129.10, 129.14,129.19, 129.27, 129.4
7, 129.86, 130.08 and 132.81(each d, C5, 6, 8, 9,1
1, 12, 14, 15, 17 and 18) （イノシトール部分） δ72.91(d, C3), 73.21(d, C2), 73.35(dd, C6), 74.11
(d, C4), 76.39(d, C5),78.49(dd, C1) （グリセロール部分） δ66.33(t, C3), 67.84(t, C1), 70.02(t, C2)31 P NMR(CD3OD)： δ2.00 FABMS （正イオンモード、マトリックス：グリセロー
ル）：m/z 641(M+H)+, 663(M+Na)+ HRFABMS ：実測値 m/z 641.2745 ［計算値m/z 641.2703
(C29H47NaO12Pとして）］ （３）活性 本発明のリゾホスファチジルイノシトールは、Mortiere
lla ramaniana に対して抗カビ活性を示した。直径８mm
のディスクに0.2mg 添加した場合に、18mmの阻止円を与
えた。The lysophosphatidylinositol of the present invention
Are as follows. 1 H NMR (CDThreeOD): (Eicosapentaenoic acid part) δ 0.96 (3H, t, J = 7.6Hz, 20-HThree), 1.68 (2H, dt, J = 14.5
and 7.4Hz, 3-HTwo), 2.08 (2H, dt, J = 14.5 and 7.3Hz, 1
9-HTwo), 2.12 (2H, m, 4-HTwo), 2.36 (2H, t, J = 7.5Hz, 2-
HTwo), 2.82 (4H, m, 7 and 16-HFour), 2.85 (4H, m, 10 and 1
3-HFour), 5.27-5.40 (10H, m, 5, 6, 8, 9, 11, 12, 14, 1
5, 17 and 18-HTen) (Inositol part) δ3.19 (1H, t, J = 9.8Hz, 5-H), 3.37 (1H, dd, J = 9.8 an
d 2.8Hz, 3-H), 3.62 (1H, t, J = 9.8Hz, 4-H), 3.76 (1H,
t, J = 9.8Hz, 6-H), 3.91 (1H, ddd, J = 9.8, 8.1 and 2.8H
z, 1-H), 4.20 (1H, t, J = 2.8Hz, 2-H) (glycerol part) δ3.97 (3H, m, 1 and 2-HThree), 4.11 (1H, dd, J = 11.4 and
5.9Hz, 3-H), 4.17 (1H, dd, J = 11.4 and 4.2Hz, 3-H)13 C NMR (CDThreeOD): (Eicosapentaenoic acid part) δ 14.65 (q, C20), 21.50 (t, C19), 25.90 (t, C3), 26.44
and 26.56 (each t, 1 × C and 3 × C, respectively,
C7, 10, 13 and16), 27.58 (t, C4), 34.34 (t, C2), 12
8.21, 128.95, 129.10, 129.14, 129.19, 129.27, 129.4
7, 129.86, 130.08 and 132.81 (each d, C5, 6, 8, 9,1
1, 12, 14, 15, 17 and 18) (Inositol part) δ72.91 (d, C3), 73.21 (d, C2), 73.35 (dd, C6), 74.11
(d, C4), 76.39 (d, C5), 78.49 (dd, C1) (glycerol part) δ 66.33 (t, C3), 67.84 (t, C1), 70.02 (t, C2)31 P NMR (CDThreeOD): δ2.00 FABMS (positive ion mode, matrix: glycerol)
M): m / z 641 (M + H)+, 663 (M + Na)+ HRFABMS: measured m / z 641.2745 [calculated m / z 641.2703
(C29H47NaO12(3) Activity The lysophosphatidylinositol of the present invention is Mortiere
It showed antifungal activity against lla ramaniana. 8mm diameter
When 0.2 mg is added to a disc, an inhibition circle of 18 mm is given.
I got it.
【００１２】また、本発明のリゾホスファチジルイノシ
トールは、ヒツジ赤血球に対してED 500.18μM で溶血活
性を示した。操作は、以下の通りである。ヒツジ保存血
液４mlに0.15M NaCl-20mM リン酸緩衝液 (pH7.4) (以下
「PBS 」という。) ６mlを加え、2500回転、７分の遠心
操作を３回繰り返して赤血球を洗浄した。得られた赤血
球に PBSを加え、２％懸濁液とした。0.5ml の懸濁液
に、蒸留水７mlを加えたときの溶血液の541nm における
吸光度を 100％溶血とし、本発明のリゾホスファチジル
イノシトールの各濃度における吸光度から50％溶血の際
の濃度を求めた。The lysophosphatidylinos of the present invention
Thor ED against sheep red blood cells 50Hemolytic activity at 0.18 μM
Showed sex. The operation is as follows. Sheep preserved blood
0.15M NaCl-20mM phosphate buffer solution (pH 7.4)
"PBS". ) Add 6 ml and centrifuge at 2500 rpm for 7 minutes
The operation was repeated three times to wash the red blood cells. Red blood obtained
PBS was added to the spheres to make a 2% suspension. 0.5ml suspension
At 541 nm of the hemolyzed blood when 7 ml of distilled water is added
The lysophosphatidyl of the present invention has an absorbance of 100% hemolysis.
50% hemolysis based on the absorbance at each concentration of inositol
Was determined.
【００１３】[0013]
【発明の効果】本発明により抗カビ剤として有用な新規
リゾホスファチジルイノシトールが提供される。According to the present invention, a novel lysophosphatidylinositol useful as an antifungal agent is provided.
───────────────────────────────────────────────────── フロントページの続き (58)調査した分野(Int.Cl.6，ＤＢ名) C07F 9/10 ＣＡ（ＳＴＮ) ＲＥＧＩＳＴＲＹ（ＳＴＮ)──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int. Cl. 6 , DB name) C07F 9/10 CA (STN) REGISTRY (STN)
Claims (2)
り抽出・精製することを特徴とする請求項１記載のリゾ
ホスファチジルイノシトールの製造法。2. The method for producing lysophosphatidylinositol according to claim 1, wherein the lysophosphatidylinositol is extracted and purified from the capsule of Halocynthia roretzi.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4640993A JP2809573B2 (en) | 1993-03-08 | 1993-03-08 | New lysophosphatidylinositol and its production method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4640993A JP2809573B2 (en) | 1993-03-08 | 1993-03-08 | New lysophosphatidylinositol and its production method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH06256366A JPH06256366A (en) | 1994-09-13 |
| JP2809573B2 true JP2809573B2 (en) | 1998-10-08 |
Family
ID=12746359
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4640993A Expired - Fee Related JP2809573B2 (en) | 1993-03-08 | 1993-03-08 | New lysophosphatidylinositol and its production method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2809573B2 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6165997A (en) * | 1997-11-20 | 2000-12-26 | Statens Serum Institut | Phospholipids having antimicrobial activity with or without the presence of antimicrobials |
| KR100491423B1 (en) * | 2002-11-22 | 2005-05-25 | 손석민 | Antimicrobial peptide isolated from Halocynthia aurantium |
-
1993
- 1993-03-08 JP JP4640993A patent/JP2809573B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JPH06256366A (en) | 1994-09-13 |
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| Date | Code | Title | Description |
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| LAPS | Cancellation because of no payment of annual fees |