synthetic study on thiostrepton macrocyclic peptide antibiotics containing many heterocyclic rings.

含多杂环的硫链丝菌素大环肽抗生素的合成研究。

• 批准号: 06640703
• 负责人: SHIN Chung-gi
• 金额: $ 1.34万
• 依托单位: Kanagawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06640703/
• 关键词: Thiostrepton antibiotics; Dehydropeptide; Dehydrothiazole; Dehydrooxazole; Multisubstituted pyridine; Micrococcin P_1; Nosiheptide; Berninamycin A; ミクロコッシンP_1; ベルニナマイシンA; デヒドロアミノ酸; チアゾールアミノ酸; チアゾールデヒドロアミノ酸; オキサゾールデヒドロアミノ酸; ペプチド抗生物質; 縮合反応

Recently, many kinds of thiostrepton macrocyclic peptide antibiotics, A10255G and J (1), berninamycin A (2), micrococcin P_1 (3), nosiheptide (4) and son have been obtained from the cultures of various strains. All of the peptides are characterized by comprising polythiazole- and -oxazole-dehydropeptide substructure (Fragment A), 2,3,6-trithiazole-substituted pyridine or 2-oxazole-3-thiazole-substituted pyridine-6-carboxylic acid moiety (Fragment B). Furthermore, interestingly, a wide variety of linear oligo-dehydroalanine or its amide segments (Fragment C) link invariably to the peptide ring. However, there is no report on the synthesis of the partial skeleton as well as the total synthesis, except for a few trisubstituted pyridine skeleton.The peculiar structures and the bioactivities attracted and prompted us to study the total synthesis and the structure-bioactivity relationship. Here, the convenient syntheses of three components called Fragments A,B,and C constituting 1-3 and 4 are described. In particular, we would like to report in detail the general syntheses of Fragments A and C starting from alpha, beta-unsaturated alpha-amino acid (alpha-dehydroamino acid) via N-carboxy alpha-dehydroamino acid anhydride. Moreover, the new synthetic methods for the Fragments B from 3-cyano-6-dimethoxymethyl-2-pyridone have been also explored.

近年来，从不同菌株的培养物中分离出多种硫链丝菌肽类抗生素，如A_（10255）G和J（1）、伯那霉素A（2）、微球菌素P_1（3）、那西肽（4）等。所有肽的特征在于包含聚噻唑-和-恶唑-脱氢肽亚结构（片段A）、2，3，6-三噻唑取代的吡啶或2-恶唑-3-噻唑取代的吡啶-6-羧酸部分（片段B）。此外，有趣的是，各种各样的线性寡聚脱氢丙氨酸或其酰胺片段（片段C）总是连接到肽环上。然而，除了少数三取代吡啶骨架外，其部分骨架的合成和全合成均未见报道，其独特的结构和生物活性吸引并促使我们对全合成及其构效关系进行研究。这里，描述了构成1-3和4的称为片段A、B和C的三种组分的方便合成。特别地，我们想要详细报道片段A和C的一般合成，其从α，β-不饱和α-氨基酸（α-脱氢氨基酸）开始经由N-羧基α-脱氢氨基酸酸酐。此外，还探索了以3-氰基-6-二甲氧基甲基-2-吡啶酮为原料合成片段B的新方法。

项目成果

C. Shin et. al.: "A conveninet synthesis of methyl2-[2-(amino)ethyenl-bithiazolyl]thiazoline 4-carboxylate, an important skeleton cyclothiazomycin" Chem. Lett.45-46 (1995)

C.辛等人。

K. Umemura et. al.: "A facile synthesis of Fragment D of antibiotic, Nosiheptide" Synthesis. 1423-1426 (1995)

K.梅村等。

C.Shin,et al.: "A Convenient Synthesis of Methyl 2-[2-(Aminoethenyl)-bithiazolyl]thiazoline-4-carboxylate,an Important Skeleton of Cyclothiazomycin" Chem.Lett.45-46 (1995)

C.Shin 等人：“2-[2-(氨基乙烯基)-联噻唑基]噻唑啉-4-甲酸甲酯的便捷合成，环噻唑霉素的重要骨架”Chem.Lett.45-46 (1995)

C.Shin et. al.: "A Convenient Synthesis of Methyl 2- [2- (Aminoethenyl) -bithiazolyl] thiazoline-4-carboxylate, an Important Skeleton of Cyclothiazomycin" Chem. Lett.1995. 45-46

C.Shin 等人。

C. Shin et. al.: "Synthesis of a common main skeleton of thiostrepton peptide antibiotics, A10255G and J" Chem. Lett.1305-1306 (1994)

C.辛等人。