JPS58164563A - Novel peptide aldehyde and its preparation - Google Patents
Novel peptide aldehyde and its preparationInfo
- Publication number
- JPS58164563A JPS58164563A JP57046277A JP4627782A JPS58164563A JP S58164563 A JPS58164563 A JP S58164563A JP 57046277 A JP57046277 A JP 57046277A JP 4627782 A JP4627782 A JP 4627782A JP S58164563 A JPS58164563 A JP S58164563A
- Authority
- JP
- Japan
- Prior art keywords
- gly
- residue
- formula
- tyr
- boc
- 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.)
- Pending
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 12
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 title 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 17
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 claims abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 9
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical group OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims abstract 4
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims abstract 3
- 150000001299 aldehydes Chemical class 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 5
- 150000004678 hydrides Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 abstract description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 8
- 230000000202 analgesic effect Effects 0.000 abstract description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 abstract description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 abstract description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 abstract 3
- 239000004471 Glycine Substances 0.000 abstract 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
- 125000006251 butylcarbonyl group Chemical group 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 abstract 1
- 239000011593 sulfur Substances 0.000 abstract 1
- 229910052717 sulfur Inorganic materials 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 239000000843 powder Substances 0.000 description 8
- 239000013078 crystal Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 6
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N Butanol Natural products CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 3
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- QPMCUNAXNMSGTK-UHFFFAOYSA-N 2-aminopropanal Chemical compound CC(N)C=O QPMCUNAXNMSGTK-UHFFFAOYSA-N 0.000 description 2
- -1 Boc group Chemical group 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 2
- GUTPQYNJVRSYHY-UHFFFAOYSA-N ethyl acetate;sulfuric acid Chemical compound OS(O)(=O)=O.CCOC(C)=O GUTPQYNJVRSYHY-UHFFFAOYSA-N 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000010446 mirabilite Substances 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- MRXDGVXSWIXTQL-HYHFHBMOSA-N (2s)-2-[[(1s)-1-(2-amino-1,4,5,6-tetrahydropyrimidin-6-yl)-2-[[(2s)-4-methyl-1-oxo-1-[[(2s)-1-oxo-3-phenylpropan-2-yl]amino]pentan-2-yl]amino]-2-oxoethyl]carbamoylamino]-3-phenylpropanoic acid Chemical compound C([C@H](NC(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C=O)C1NC(N)=NCC1)C(O)=O)C1=CC=CC=C1 MRXDGVXSWIXTQL-HYHFHBMOSA-N 0.000 description 1
- IJWCGVPEDDQUDE-YGJAXBLXSA-N (2s)-2-[[(1s)-2-[[(2s)-5-amino-1,5-dioxo-1-[[(2s)-1-oxopropan-2-yl]amino]pentan-2-yl]amino]-1-[(6s)-2-amino-1,4,5,6-tetrahydropyrimidin-6-yl]-2-oxoethyl]carbamoylamino]-4-methylpentanoic acid Chemical compound O=C[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)N[C@@H](CC(C)C)C(O)=O)[C@@H]1CCN=C(N)N1 IJWCGVPEDDQUDE-YGJAXBLXSA-N 0.000 description 1
- CQIUZHAQYHXKRY-VIFPVBQESA-N (2s)-2-amino-3-phenylpropanal Chemical compound O=C[C@@H](N)CC1=CC=CC=C1 CQIUZHAQYHXKRY-VIFPVBQESA-N 0.000 description 1
- CNBUSIJNWNXLQQ-NSHDSACASA-N (2s)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CNBUSIJNWNXLQQ-NSHDSACASA-N 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- OLVPQBGMUGIKIW-UHFFFAOYSA-N Chymostatin Natural products C=1C=CC=CC=1CC(C=O)NC(=O)C(C(C)CC)NC(=O)C(C1NC(N)=NCC1)NC(=O)NC(C(O)=O)CC1=CC=CC=C1 OLVPQBGMUGIKIW-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- IJWCGVPEDDQUDE-UHFFFAOYSA-N Elastatinal Natural products O=CC(C)NC(=O)C(CCC(N)=O)NC(=O)C(NC(=O)NC(CC(C)C)C(O)=O)C1CCN=C(N)N1 IJWCGVPEDDQUDE-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical class [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- ATWGHWZRHOJITC-UHFFFAOYSA-N [S].C1=CC=NC=C1 Chemical compound [S].C1=CC=NC=C1 ATWGHWZRHOJITC-UHFFFAOYSA-N 0.000 description 1
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000767 anti-ulcer Effects 0.000 description 1
- RTEXIPZMMDUXMR-UHFFFAOYSA-N benzene;ethyl acetate Chemical compound CCOC(C)=O.C1=CC=CC=C1 RTEXIPZMMDUXMR-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 108010086192 chymostatin Proteins 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 108010039262 elastatinal Proteins 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- DANUORFCFTYTSZ-UHFFFAOYSA-N epinigericin Natural products O1C2(C(CC(C)(O2)C2OC(C)(CC2)C2C(CC(O2)C2C(CC(C)C(O)(CO)O2)C)C)C)C(C)C(OC)CC1CC1CCC(C)C(C(C)C(O)=O)O1 DANUORFCFTYTSZ-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical group CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Abstract
Description
【発明の詳細な説明】
本発明は新規なペプチドアルデヒド類及びその酸付加塩
並びにそれらの製造法に関するものである◎
本発明の化合物は文献未載の新規化合物であり
一般式
（式中ｘ：Ｈ又は（ＣＨｓ ）ｓ Ｃｏｃｏ 、Ａ ：
ＣＨａ ＆−ＣＨ５−Ｃ賜−ＣＨ＜又は”＞ＣＨ−Ｃ
ｋｂＣＨ＜を示す）で示されるペプチ１
ドアルデヒド類である。本発明の化合物は鎮痛薬及びそ
の合成中間体としての用途が期待される化合物である◎
ペプチドアルデヒド類は微生物が産生ずる酵素阻害剤と
してこれまでにロイペプチン、キモスタチン、エラスタ
チナールが見出されているが、これらはＣ末端残基とし
てアラニナール。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to novel peptide aldehydes, acid addition salts thereof, and methods for producing them.◎ The compound of the present invention is a novel compound that has not been described in any literature and has the general formula (in the formula x: H or (CHs)s Coco, A:
CHa &-CH5-C gift-CH<or”>CH-C
It is a peptidaldehyde represented by kbCH<). The compound of the present invention is a compound that is expected to be used as an analgesic and its synthetic intermediate. ◎ Peptide aldehydes include leupeptin, chymostatin, and elastatinal, which have been discovered as enzyme inhibitors produced by microorganisms. However, these have alaninal as the C-terminal residue.
フェニルアラニナール、アラニナールをそれでれ含んで
いる。Contains phenylalaninal and alaninal.
これらペプチドアルデヒド類は各種グロテアーゼ例えば
プラスミン、パパイン、キモトリプンン等を強く阻害す
るが、これら阻害剤は消炎作用、抗潰瘍作用、変異誘発
阻止９発癌並びに癌転鰯阻止など多くの疾病に対する効
果が報告されている。These peptide aldehydes strongly inhibit various groteases, such as plasmin, papain, and chymotryphin, and these inhibitors have been reported to have effects on many diseases, such as anti-inflammatory effects, anti-ulcer effects, inhibition of mutagenesis9 carcinogenesis, and inhibition of cancer metastasis. ing.
本発明者等はこれらペプチドアルデヒドアナログの開発
を目的としてペプチドアルデヒド類を合成し９種々薬理
活性についてスクリーニングテストを行った結果９本発
明の化合物が強い鎮痛作用のあることを見出し本発明を
完成した。The present inventors synthesized peptide aldehydes for the purpose of developing these peptide aldehyde analogs, conducted screening tests for various pharmacological activities, and found that the compounds of the present invention have a strong analgesic effect, thereby completing the present invention. .
本発明に係る新規化合物は次の方法で合成することが出
来る。The novel compound according to the present invention can be synthesized by the following method.
合成工程は第一工程の還元工程と第二工程の酸化工程か
らなっており、先ず第一工程の還元工程にライて説明す
るど文献Ｂ、Ｖｉｌｋａｓ ｅｔ ａｌ、。The synthesis process consists of a first step, a reduction step, and a second step, an oxidation step.First, the first step, a reduction step, will be explained as described in Document B, Vilkas et al.
Ｊ、Ｐｅｐｔ、Ｒｅｓ、、 １５．２９ （１９８０）
及びＲ，Ｃ，Ｈｉｌｌ ｅｔ ａｌ、。J.Pept.Res., 15.29 (1980)
and R.C., Hill et al.
Ｎａｔｕｒｅ、 ２６１．４２３ （１９７６）に記載
されている方法に従い容易に合成することの出来るＢｏ
ｃ−Ｔｙｒ −（］ｌ ｙ−Ｇｌ ｙ−Ｐｈｅ−Ｌｅｕ
−４）Ｑ（３及びＢｏｃ−Ｔｙｒ −Ｇｌ ｙ−０１ｙ
−Ｐｈ ｅ −Ｍｅ ｔ−ＯＣＨ３をテトラヒドロフラ
ン等の有機溶媒と混合し、アルゴンガス等の不活性ガス
気流下に塩化リチウム及び水素化ホウ素ナトリウムを作
用させることによってＮ末端アミノ基をＢｏｃ基で保護
したペプチドアルコール類（以下Ｂｏｃ−ペプチドアル
コール類と略す）とする。Bo, which can be easily synthesized according to the method described in Nature, 261.423 (1976).
c-Tyr-(]ly-Gly-Phe-Leu
-4) Q(3 and Boc-Tyr -Gly-01y
-Ph e -Me t-OCH3 was mixed with an organic solvent such as tetrahydrofuran, and the N-terminal amino group was protected with a Boc group by reacting with lithium chloride and sodium borohydride under a stream of inert gas such as argon gas. Peptide alcohols (hereinafter abbreviated as Boc-peptide alcohols).
この反応は通常室温で行う場合約２０数時間で反応は完
結する。後処理方法としては反応液にクエン酸溶液を加
え、水層を酢酸エチル等の有機溶媒で抽出し、クエン酸
水溶液、飽和重費水。This reaction is usually completed in about 20 hours when carried out at room temperature. As a post-treatment method, add citric acid solution to the reaction solution, extract the aqueous layer with an organic solvent such as ethyl acetate, and add citric acid aqueous solution and saturated heavy water.
水で順次洗浄し、芒硝で乾燥した後、溶媒を留去するこ
とによって結晶として単離することが出来る。得られた
生成物はそのまま次の第二工程の原料として使用するこ
とも出来るが、適当な溶媒で再結晶精製を行い次の反応
に使用する方が好ましい。It can be isolated as crystals by sequentially washing with water, drying with Glauber's salt, and then distilling off the solvent. Although the obtained product can be used as it is as a raw material for the next second step, it is preferable to perform recrystallization purification with an appropriate solvent and use it for the next reaction.
次に第二工程の酸化工程について説明すると第一工程で
得られたＢｏｃ−ペプチドアルコール類を無水ジメチル
スルホキシドと混合しトリエチルアミン、三酸化イオウ
錯体の無水ジメチルスルホキシド溶液を添加して室温で
酸化することによってＮ末端アミン基をＢｏｃ基で保護
したペプチドアルデヒド類（以下Ｂｏｃ−ペプチドアル
デヒド類と略す）とすることが出来る。使用するトリエ
チルアミンと三酸化イオウ錯体の量は２５当量あれば充
分であるが、約８当量使用する条件が適当である。三酸
化イオウ酸体としては三酸化イオウとピリジン、ジオキ
サン、トリメチルアミン、又はＤ Ｍ Ｆ”等との錯体
が使用できる。反応温度は室温が好ましく反応時間は数
分〜士数分で充分である。Next, to explain the second oxidation step, the Boc-peptide alcohol obtained in the first step is mixed with anhydrous dimethyl sulfoxide, and a solution of triethylamine and sulfur trioxide complex in anhydrous dimethyl sulfoxide is added to oxidize at room temperature. Peptide aldehydes (hereinafter abbreviated as Boc-peptide aldehydes) in which the N-terminal amine group is protected with a Boc group can be obtained by the following steps. It is sufficient to use 25 equivalents of the triethylamine and sulfur trioxide complex, but it is appropriate to use about 8 equivalents. As the sulfuric acid trioxide, a complex of sulfur trioxide and pyridine, dioxane, trimethylamine, DMF" or the like can be used. The reaction temperature is preferably room temperature, and the reaction time is preferably several minutes to several minutes.
溶媒としては無水ジメチルスルホキシドがその働らきを
するが、必要によりベンゼン、塩化メチレン等も使用出
来る。Anhydrous dimethyl sulfoxide serves as the solvent, but benzene, methylene chloride, etc. can also be used if necessary.
後処理方法としては反応混合物を氷水中にあけ、生成物
を適宜の溶媒１例えばエーテルあるいハ酢酸エチルーベ
ンゼ／（４：１）に溶解し。As a work-up method, the reaction mixture was poured into ice water, and the product was dissolved in a suitable solvent such as ether or ethyl acetate/benzene/(4:1).
クエン酸水溶液、水、飽和重曽水で順次洗浄した後乾燥
し、溶媒を留去することによりＢｏｃ−ペプチドアルデ
ヒド類を得る。得られた粗結晶は例えば酢酸エチルーー
ーテル溶媒等９通常の方法を用いて再結晶精製すること
が出来る。Boc-peptide aldehydes are obtained by sequentially washing with an aqueous citric acid solution, water, and saturated sodium chloride solution, drying, and distilling off the solvent. The obtained crude crystals can be purified by recrystallization using a conventional method such as ethyl acetate ether solvent.
更に、酸付加塩を得る丸めには常法の手段で処理すれば
よいが９例えばＢｏｃ−ペプチドアルデヒド類をアセト
ニトリル等の溶媒に溶解し。Further, rounding to obtain an acid addition salt may be carried out by a conventional method.9 For example, Boc-peptide aldehydes are dissolved in a solvent such as acetonitrile.
塩化水素−酢酸エチル溶液又はＰ−）ルエンスルホン酸
−酢酸エチル溶液又は硫酸−酢酸エチル溶液を加え室温
で反応することにより保鏝基は脱離される・次いで反応
液にエーテル等の溶媒を加え結晶を析出させた後、これ
を口取すれば塩酸塩、Ｐ−）ルエンスルホン酸塩又は硫
酸塩として得られる０尚、必要であれば上記酸付加塩の
水溶液を市販されている弱塩基性樹脂を詰めた力、ラム
に通し１通通液を得、この溶液を低温で減圧濃縮し、ア
セトン等の有機溶媒を加えれば結晶が析出する。これを
口取するか、あるいは通過液を凍結乾燥すれば
（式中Ａは前記と同様）を結晶として得ることとができ
る。Hydrogen chloride-ethyl acetate solution, P-)luenesulfonic acid-ethyl acetate solution or sulfuric acid-ethyl acetate solution is added and the sulfuric acid-ethyl acetate solution is added and reacted at room temperature to remove the anchor group.Next, a solvent such as ether is added to the reaction solution to form crystals. After precipitating, the aqueous solution of the above acid addition salt can be added to a commercially available weak basic resin if necessary. Pass the solution through a ram packed with water to obtain one solution, concentrate this solution under reduced pressure at low temperature, and add an organic solvent such as acetone to precipitate crystals. If this is taken or the passed liquid is freeze-dried (wherein A is the same as above), it can be obtained as crystals.
次に参考例及び実施例を以て本発明を説明するが９本発
明の範囲がこれにより限定されるものではない。Next, the present invention will be explained using reference examples and examples, but the scope of the present invention is not limited thereto.
尚文中の略号は各々次の意味を表わすものとする。The abbreviations in the text shall each represent the following meanings.
Ｔｙｒ：チロシン残基
Ｇｌｙニゲリシン残基
Ｐｈｅ ：フェニルアラニン残基
Ｌｅｕ：ロイシン残基
Ｍｅｔ：メチオニン残基
Ｂｏｃ ：第三ブトキシカルボニル基
０１ニアミノ酸残基の略号と共に用いβ−アミノアルコ
ールを示す
ａ１ニアミノ酸残基の略号と共に用いα−アミノアルデ
ヒドを示す
ＯＭｅ ：メチルエステル
参考例１． Ｂｏｃ −Ｌ−Ｔｙ ｒ−Ｇｌ ｙ−Ｇ
ｌ ｙ−レＰｈｅ−Ｌ−Ｌｅ ｕ−〇ｌの合成
アルゴンガスで置換した反応容器内にＢｏｃ−Ｌ−Ｔｙ
ｒ−０１ｙ−Ｇｌ ｙ−レＰｈｅ−Ｌ−Ｌｅｕ−ＯＭｅ
ｌＪ８９（２ミリモル）とテトラハイドロフラン４
履ｌの溶液を入れ、塩化リチウム２５４Ｉｎ９（６ミリ
モル）水素化ホウ′素ナトリウム２２８■（６ミリモル
）とエタノール２０−を加え、アルゴン下に室温２４時
間反応する。１０％クエン酸水溶液６０ｍ１を反応溶液
に加え、水層を酢酸エチル８０ｍ／で２回抽出し、酢酸
エチル層は１０％クエン酸水溶液８０ｍ／、水３Ｑｍ／
、飽和重曽水８０１１／で各１回洗い、芒硝乾燥した。Tyr: tyrosine residue Gly nigericine residue Phe: phenylalanine residue Leu: leucine residue Met: methionine residue Boc: tertiary butoxycarbonyl group a1 diamino acid residue used with the abbreviation of 01 diamino acid residue to indicate β-amino alcohol OMe used with group abbreviations to indicate α-aminoaldehyde: Methyl ester reference example 1. Boc-L-Tyr-Gly-G
Synthesis of Boc-L-Ty in a reaction vessel purged with argon gas.
r-01y-Gly-Phe-L-Leu-OMe
lJ89 (2 mmol) and tetrahydrofuran 4
To the mixture were added 254 l of lithium chloride (6 mmol), 228 l of sodium borohydride (6 mmol) and 20 l of ethanol, and the mixture was allowed to react at room temperature under argon for 24 hours. 60 ml of 10% citric acid aqueous solution was added to the reaction solution, and the aqueous layer was extracted twice with 80 ml of ethyl acetate.
, washed once each with saturated heavy-duty water 8011/ml, and dried with Glauber's salt.
溶媒留去後酢酸エチルより再結晶し無色の粉末を得た。After distilling off the solvent, the residue was recrystallized from ethyl acetate to obtain a colorless powder.
収量ｌ。０８ｐ（８５％）、融点； １１５〜１２２℃
。Yield l. 08p (85%), melting point; 115-122°C
.
ＩＲｖ：實’ Ｃｒｒｒ’； ３２８０．１７００．１
６８０．１５１５゜ＮＭＲ（ｄ、−ＤＭＳＯ）；０．６
７−１４）（６Ｈ，ｍ）、 １．２８（９Ｈ，Ｓ）。IRv:Actually 'Crrr'; 3280.1700.1
680.1515°NMR (d,-DMSO); 0.6
7-14) (6H, m), 1.28 (9H, S).
６．５−７．１（４Ｈ，ＡＢ、８Ｈｚ）、 ７．２８゜
参考例２． Ｂｏａ−Ｉ、Ｔｙｒ−０１ｙ−Ｇｌｙ−
レＰｈｅ−ＩＪ−Ｍ ｅ ｔ −ｏ １の合成
参考例１と同様にＢｏ ｃ −Ｌ−Ｔｙ ｒ−Ｇｌ ｙ
−Ｇｌ ｙ −Ｌ−Ｐｈｅ−１，−Ｍｅｔ −ＯＭｅ
１．１８ｇ（１，６６ミリモル）、塩化リチウム２８２
■（６６４ミリモル）、水素化ホウ素ナトリウムｗ５１
ｍｇ （６，６４ミリモル）、テトラハイドロフラン８
履！及びエタノール１６ｍ／を用いて反応し、参考例１
■と同様に後処理した。6.5-7.1 (4H, AB, 8Hz), 7.28° Reference Example 2. Boa-I, Tyr-01y-Gly-
Boc-L-Tyr-Gly
-Gly -L-Phe-1, -Met -OMe
1.18 g (1.66 mmol), lithium chloride 282
■(664 mmol), sodium borohydride w51
mg (6.64 mmol), tetrahydrofuran 8
Wear! and 16 m/ethanol, and the reaction was carried out using Reference Example 1.
Post-processing was carried out in the same manner as in ①.
溶媒留去後酢酸エチルより再結晶し無色粉末を得た。After the solvent was distilled off, the residue was recrystallized from ethyl acetate to obtain a colorless powder.
収量９５５Ｉｎｇ（８８％ ）、融点１２０〜１２５℃
０ＩＲｖ以豐Ｃｍ−’： １３２８０．１７００．１６
３０．１５２０゜ＮＭＲ（ｄ６−ＤＭＳＯ） ； １．
２６（９Ｉ（、Ｓ）、 ８．７８（４Ｈ，ＡＢ、８Ｈｚ
）。Yield 955Ing (88%), melting point 120-125℃
0IRvCm-': 13280.1700.16
30.1520°NMR (d6-DMSO); 1.
26 (9I (, S), 8.78 (4H, AB, 8Hz
).
７．１３（５）（，８）、 ８．９８（ＬＨ，Ｓ）。7.13(5)(,8), 8.98(LH,S).
実施例１． ｒ３ｏｃ−Ｌ−Ｔｙｒ−Ｇｌｙ−Ｇｌｙ
−レーＰｈｅ−Ｌ−Ｌｅｕ−ａ１の合成
りｏｃ−Ｌ−Ｔｙ ｒ−０１ｙ−Ｇｌ ｙ＝１．−Ｐｈ
ｅ−Ｌ−Ｌｅｕ−ｏ Ｉ ３１８ｍｇ （０，５ミリモ
ル）、トリエチルアミン２０２１ｎ９（２ミリモル）、
無水ジメチルスルホキシド２ｍｌ溶液に、室温攪拌下三
酸化イオウーピリジン錯体１３１８１Ｑ （２ミＩＪモ
ル）の無水ジメチルスルホキシト溶’Ｑ ２ ｍｔを加
え、１０分間攪拌反応させた。この反応溶液に酢酸エチ
ル−ベンゼン（４：１．溶量比）１５０ｍ／を加え、１
０％クエン酸水溶’０２０ ｍｌで２回、水２０ ｍｌ
で２回、飽和重曹水２０ｍ１で洗い、無水芒硝で乾燥し
た。Example 1. r3oc-L-Tyr-Gly-Gly
- Synthesis of Phe-L-Leu-a1 oc-L-Tyr-01y-Gly=1. -Ph
e-L-Leu-o I 318 mg (0.5 mmol), triethylamine 2021n9 (2 mmol),
A solution of sulfur pyridine trioxide complex 13181Q (2 mmol) in anhydrous dimethyl sulfoxide was added to 2 ml of anhydrous dimethyl sulfoxide solution with stirring at room temperature, and the mixture was reacted with stirring for 10 minutes. To this reaction solution was added 150 m/ethyl acetate-benzene (4:1.
0% citric acid aqueous solution '020 ml twice, 20 ml of water
It was washed twice with 20 ml of saturated sodium bicarbonate solution, and dried over anhydrous sodium sulfate.
溶媒留去後残渣を酢酸エチル−エーテルで再結晶し無色
の粉末を得た。After evaporating the solvent, the residue was recrystallized from ethyl acetate-ether to obtain a colorless powder.
収量１９５ｍｐ（収率６１％）、融点； １６０〜１６
５℃。Yield 195mp (yield 61%), melting point; 160-16
5℃.
〔α）Ｈ−３２，９（ｃ＝＝ １． ジメチルホルム
アミド）。[α) H-32,9 (c== 1. dimethylformamide).
実施例２． Ｂｏｃ−Ｌ−Ｔｙｒ−０１ｙ−Ｇｌｙ−
Ｌ−Ｐｈｅ−Ｌ−Ｍｅｔ −ａｌの合成
りｏｃ−Ｌ−Ｔｙ ｒ−０１ｙ−Ｇｌ ｙ−Ｌ−Ｐｈｅ
−Ｌ−Ｍｅ ｔ −ｏ １３２７ｍＬ？（０，５ミリ
モル）、トリエチルアミン２０２ｍ９（２ミリモル）、
三酸化イオウ−ピリジン錯体３１８ｍｙ （２ミリモル
）と無水ンメチルスルホキシド４ｍｌを用いて１０分間
攪拌反応させた。その後実施例１と同様に操作し、無色
の粉末である目的物を得た。収量２３５ｍ９（収率７２
％）、融点； １１５〜１２０℃（分解）。Example 2. Boc-L-Tyr-01y-Gly-
Synthesis of L-Phe-L-Met-aloc-L-Tyr-01y-Gly-L-Phe
-L-Met-o 1327mL? (0.5 mmol), triethylamine 202m9 (2 mmol),
A reaction was carried out with stirring for 10 minutes using 318 my (2 mmol) of sulfur trioxide-pyridine complex and 4 ml of anhydrous methyl sulfoxide. Thereafter, the same procedure as in Example 1 was carried out to obtain the desired product as a colorless powder. Yield 235m9 (Yield 72
%), melting point; 115-120°C (decomposition).
〔６片−３２（Ｃ＝ １． ジメチルホルムアミド）
。[6 pieces-32 (C=1. dimethylformamide)
.
実施例８． ＨＣＩ・Ｈ−Ｌ−Ｔｙｒ−Ｇｌｙ−（Ｊ
ｌｙ−Ｌ−Ｐｈｅ−レ■）ｅｕ−ａｔの合成
りｏｃ −Ｉｊ−Ｔｙ ｒ−０１ｙ−Ｇｌ ｙ−Ｌ＝Ｐ
ｈｅ−Ｌ−Ｌｅｕ−ａ １２００〜（０３２ミリモル）
のアセトニトリル４ｍｌ溶液に２３規定塩化水素−酢酸
エチル１２ｉｌを加え、室温で２０分間攪拌した後、無
水エーテル１５ｍＪを加えると結晶が析出する。これを
口取し無色の粉末を得た。収量１０５ｍ９（収率５８４
係）、融点；１３５℃で湿潤、１６５℃で発泡して膨張
、１９０〜２１０°Ｃで着色分解。この粉末は薄層クロ
マトグラフィー（以下ＴＬＣと略す）により確認した。Example 8. HCI・HL-Tyr-Gly-(J
ly-L-Phe-Le ■) Synthesis of eu-at oc-Ij-Tyr-01y-Gly y-L=P
he-L-Leu-a 1200~(032 mmol)
To 4 ml of acetonitrile solution was added 12 il of 23N hydrogen chloride-ethyl acetate, stirred at room temperature for 20 minutes, and then 15 mJ of anhydrous ether was added to precipitate crystals. This was taken out to obtain a colorless powder. Yield 105m9 (Yield 584
), melting point: moist at 135°C, foam and expand at 165°C, color decomposition at 190-210°C. This powder was confirmed by thin layer chromatography (hereinafter abbreviated as TLC).
シリカゲ／ｌ／ Ｔ Ｌ Ｃ（Ｍｅｒｃｋ社製Ｌ 社製
−ブタノール：酢酸：水（７：ａ：ａ）でＲｆ値０６９
゜ｎ−ブタノール：酢酸：ピリジン：水（８０：６：２
４：２０）でＲ，ｆ値０７２゜逆相ｊＬＣ（Ｗｈａｔｍ
ａｒｎ社製、 ＫＣ，−１，−８Ｆ）ｌ’ ８０ ％
含水メタノールでＲｆ値０６６を示す。Silicage/L/TLC (manufactured by Merck Company L - butanol:acetic acid:water (7:a:a) with Rf value of 069
゜n-Butanol: Acetic acid: Pyridine: Water (80:6:2
4:20), R, f value 072° reverse phase jLC (Whatm
Manufactured by ARN, KC, -1, -8F) l' 80%
It shows an Rf value of 066 in aqueous methanol.
〔α〕賃モモ８１６（Ｃ＝ ０．３’、水）、 ＩＲ
（Ｎｕｊｏｌ）；８２２０ ＣＩｌ＋ ’ （−ＮＨ３
，−ＮＨＣＯ−）、 ］、 ７７２５ｃｍ１’−ＣＨ＝
０ ）、 １６！１０ｃｆｒ”（ＮＨＣＯ）、１Ｂ１
０ｃａ’（Ｎｉ（ＣＯ）。[α] Momo 816 (C = 0.3', water), IR
(Nujol);8220 CIl+' (-NH3
, -NHCO-), ], 7725cm1'-CH=
0), 16!10cfr” (NHCO), 1B1
0ca'(Ni(CO).
ＮＭＲ（ＴＭ８／ｄ、−ＤＭ８０）；０．８６（ｅＨ，
ｒ１％ −ｃｕ（ｃ鴇Ｎ６．８６（４Ｈ，ＡＢ、−◎−
０Ｈ） ？、ＩＯ（！ｉＨ，８，−Ｐｈ）８．９０ （
１）Ｌ ｂＪ、 −Ｐｂ０（）、 ９Ｊｌ（ｌ）ｉ、８
．−ＣＨ＝０）〜
実施例４ ＨＣＩ−Ｈ−Ｌ−Ｔｙｒ−Ｇｌｙ−Ｇｌｙ
−レＰｈｅ−Ｌ−Ｍｅｔ−ｍｌの合成
りｏｃ −Ｌ−７ｙ ｒ −Ｇｌ ｙ−Ｇｌ ｙ−Ｌ−
Ｐｈｅ −Ｌ−Ｍｅ ｔ−ａ １１６４１１１９（０１
５ミリモル）のアセトニトリル８一嬉液番ζ８．８規定
の塩化水素−酢酸エチル９１１Ｊを加え、Ｗ１温でＳＯ
＋間攪拌すると結晶が析出する。無水エーテル９−を加
え、これを口取すると無色粉末が得られる。収量１４１
１９ （収率１００％）、融点；１１０℃でａＲｍ
ｘｓｌｓ℃より発泡して膨張、１６６〜１７０℃で着色
分解。NMR (TM8/d, -DM80); 0.86 (eH,
r1% -cu(c 錇N6.86(4H, AB, -◎-
0H)? , IO(!iH,8,-Ph)8.90 (
1) L bJ, -Pb0(), 9Jl(l)i, 8
．． -CH=0) ~ Example 4 HCI-HL-Tyr-Gly-Gly
- Synthesis of Phe-L-Met-ml -L-7yr -Gly-Gly-L-
Phe-L-Me ta 11641119 (01
Add 911 J of acetonitrile (5 mmol) of acetonitrile 8.8 normal hydrogen chloride-ethyl acetate, and add SO at W1 temperature.
If the mixture is stirred for + time, crystals will precipitate. Anhydrous ether 9- is added and this is taken to give a colorless powder. Yield 141
19 (yield 100%), melting point; aRm at 110°C
Foams and expands from xsls°C, and discolors and decomposes at 166-170°C.
この粉末の純度はＴＬＣにより確■し九。シリカゲＡ／
Ｔ Ｌ Ｃ（Ｍｅｒｃｋ社製）ｎ−ブタノール：酢酸：
水（？：８：８）でＲｆ ＠［Ｏ，？８． ｎ−ブタノ
ール：酢酸：ピリジン：水（８０：６：ｉ１４：ｚＯ）
でＲｆ値０．７１０
逆相Ｔ Ｌ Ｃ（Ｗｈａｔｍａｒｎ社製）ｅｓｏ’ｌ含
水メタノールでＲｆｏ、６１を示す。The purity of this powder was confirmed by TLC. Silikage A/
TLC (manufactured by Merck) n-butanol: acetic acid:
Rf @[O,? on water (?:8:8) 8. n-butanol:acetic acid:pyridine:water (80:6:i14:zO)
The Rf value is 0.710, and the Rfo is 61 in reverse phase TLC (manufactured by Whatmarn) eso'l aqueous methanol.
（ｃｘ）ｇ ＋ ｍｓ、ｏ （ｃ ＝ ｏ、８．水）
、 Ｉ Ｒ（Ｎｕｊｏｌ ）；ａＩＯｃｍ−’（−ＮＨ
，、ＮＨＣＯ）、 １７２５ｃａ＋１（−ＣＨ＝０ ）
、 １６６０ｃｍ−１（−ＮＨＣＯ−）、 １５１１
ｓｃａ”（ＮＨＣＯ）ＮＭＲ（ＴＭ８／ｄ、−ＤＭ８０
） ： ｓ、ｏ （ｓＨ，８，−８０Ｈ，）。(cx) g + ms, o (c = o, 8. water)
, IR(Nujol);aIOcm-'(-NH
,,NHCO), 1725ca+1(-CH=0)
, 1660cm-1(-NHCO-), 1511
sca” (NHCO) NMR (TM8/d, -DM80
): s, o (sH, 8, -80H,).
ａ、５ｅ（４Ｈ，ＡＢ、 −＠ＯＨ）、 ｙ、ｇｇ（５
Ｈ，８，−Ｐｈ）。a, 5e (4H, AB, -@OH), y, gg (5
H,8,-Ph).
８．９０（ＩＨ，ｂ、ｓ；、、 −ＰｈＯＨ）、 ９
．ｉ１６ （ＩＨ，８゜−ＣＨ＝０）8.90 (IH, b, s;, -PhOH), 9
．． i16 (IH, 8°-CH=0)
Claims (5)
）（Ｊ＞ＣＨ−ＣＨ，−ＯＨ＜を示す）で表わされるベ
プＨｍ チドアルデヒド類(1) General formula (in the formula: CH,8-C-CHs-CM<or 0
) (indicating J>CH-CH, -OH<)
化合物(2) Compounds referred to in Claims No.-1 in the form of acid addition salts
ｏｃ基で保躾されている特許請求の範囲第一項記載の化
合物(3) The α-azuno group of tyrosine constituting the peptide is B
Compound according to claim 1 protected by oc group
２エン及びＡがＬ一体である特ｔｆｌ１１１求の範囲第
一項記載の化合物(4) Tyrosine and phenyla that compose the peptide 8
Compounds according to item 1, in which 2-ene and A are L-units.
（Ｊ＞ＣＨ−ＣＨｓ−ＣＨ＜を示す）で表わされるベプ
ＣＨ。 チドアルコール類にジメチルスルホキシド中トリエチル
アミン存在下三酸化イオウ錯体を反応させることを特徴
とする・ 一般式 （式中人は前記と同様） で表わされるペプチドアルデヒド類の製造法(5) General formula (in the formula, AFiCt is 8-CHICHI-CH<or 0)
(denoting J>CH-CHs-CH<). A method for producing peptide aldehydes represented by the general formula (the characters in the formula are the same as above), which is characterized by reacting a hydride alcohol with a sulfur trioxide complex in dimethyl sulfoxide in the presence of triethylamine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57046277A JPS58164563A (en) | 1982-03-25 | 1982-03-25 | Novel peptide aldehyde and its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP57046277A JPS58164563A (en) | 1982-03-25 | 1982-03-25 | Novel peptide aldehyde and its preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS58164563A true JPS58164563A (en) | 1983-09-29 |
Family
ID=12742725
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57046277A Pending JPS58164563A (en) | 1982-03-25 | 1982-03-25 | Novel peptide aldehyde and its preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS58164563A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5760002A (en) * | 1992-12-22 | 1998-06-02 | The Proctor & Gamble Company | Diflouro pentapeptide derivative anti-inflammatory agents |
-
1982
- 1982-03-25 JP JP57046277A patent/JPS58164563A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5760002A (en) * | 1992-12-22 | 1998-06-02 | The Proctor & Gamble Company | Diflouro pentapeptide derivative anti-inflammatory agents |
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