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Bio-organic Synthesis of Several Antibiotics from Polyketide Lactone.

从聚酮内酯生物有机合成几种抗生素。

基本信息

批准号：
05453133
负责人：
TATSUTA Kuniaki
金额：
$ 4.74万
依托单位：
Waseda University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05453133/
关键词：
Macrolide Pyranonaphthoquinone Poliketide Oleandomycin Naphthopyran Aldol condensation グリコシル化

项目摘要

It is generally accepted that many kinds of natural antibiotics such as macrolides, tetracyclines, and napthopyrans are biochemically synthesized from polyketide chains (beta-polyoxoalkanoates). Much chemical effort has been devoted to the synthetic studies of polyketide chains, with have been the subject of a recent comprehensive review. A cyclic polyketide (polyketide lactone) was synthesized from naturally derived macrolide aglycone in our laboratorines. Herein, we report the first synthesis and X-ray analysis of a stable 14-membered polyketide lactone, which would be submitted to hydride reduction and aldol cyclization as biomimetic syntheses of macrolide and naphthopyran antibiotics.The synthesis of the polyketide lactone began with Fremy's radical oxidation. Exhaustive ozonolysis of the tricyclic 5-6-7-memberd compound gave the stable polyketide lactone, the structue of which was determined by the X-ray crystallographic analysis to be present as the bis-enol from.Sodium borohydride reduction of the polyketide lactone gave eight isomers of the tetraols, which were corresponding to the aglycone of the macrolide antibiotics. The relative stereochemistry of three of the tetraols was also determined by the X-ray analyzes.The intra-molecular aldolization of the polyketide lactone was assayd under a variety of conditions and the best result was realized by usung KOAc in MeOH to give one major product, which was the orecursor of antifungal naphthopyran, semivioxanthin.Now that the stable polyketide lactone has been efficiently obtained as the bis-enol from, the further biomimetic derivation is the subject of current studies.

人们普遍认为，许多种类的天然抗生素，如大环内酯类、四环素类和萘并吡喃类，都是由聚酮链（β-聚氧烷酸酯）生物化学合成的。聚酮化合物链的合成研究已成为化学界的一项重要研究，最近的研究也取得了很大进展。我们实验室以天然大环内酯苷元为原料合成了环状聚酮（聚酮内酯）。本文报道了一种稳定的14元聚酮内酯的首次合成和X-射线分析，该化合物可通过氢化物还原和羟醛缩合等仿生合成大环内酯和萘并吡喃类抗生素，其合成起始于Fremy自由基氧化反应。三环5-6-7-元化合物经臭氧分解得到稳定的聚酮内酯，经X-射线晶体学分析确定其结构为双烯醇，硼氢化钠还原聚酮内酯得到八个四醇异构体，它们对应于大环内酯类抗生素的糖苷配基。用X-射线衍射法测定了三种四醇的相对立体化学结构，并在不同条件下对聚酮内酯的分子内羟醛缩合反应进行了研究，结果表明，用乙酸钾在甲醇中进行羟醛缩合反应，得到的主要产物是抗真菌剂萘并吡喃的前体半紫黄质。进一步的仿生衍生是当前研究的主题。