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

近年来，从各种菌株的培养中获得了多种硫链霉素大环肽抗生素，A10255G和J(1)，贝尼霉素A(2)，微球菌素P_1(3)，诺西肽(4)等。所有肽的特征是包含多噻唑-和-恶唑-脱氢肽亚结构（片段A）， 2,3,6-三噻唑-取代吡啶或2-恶唑-3-噻唑-取代吡啶-6-羧酸片段（片段B）。此外，有趣的是，各种各样的线性低聚脱氢丙氨酸或其酰胺片段（片段C）总是连接到肽环上。但除少数三取代吡啶骨架外，未见部分骨架和全骨架的合成报道。其独特的结构和生物活性吸引并促使我们对其全合成和结构-生物活性关系进行研究。在这里，描述了组成1-3和4的三个组分，称为片段A，B和C的方便合成。特别是，我们想详细报道从α， β -不饱和α -氨基酸（α -脱氢氨基酸）开始，通过n -羧基α -脱氢氨基酸酸酐合成片段A和C的一般方法。此外，还探索了由3-氰基-6-二甲氧基甲基-2-吡啶酮合成片段B的新方法。

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.