Bio-organic Synthesis of Several Antibiotics from Polyketide Lactone.

人们普遍认为，许多天然抗生素如大环内酯类、四环素类和萘吡喃类都是由聚酮链（β -聚氧烷酸酯）生物合成的。聚酮链的合成研究已经投入了大量的化学努力，并已成为最近全面审查的主题。以天然大环内酯苷元为原料合成了环状聚酮（聚酮内酯）。本文首次合成了一种稳定的14元聚酮内酯，并进行了x射线分析，该聚酮内酯将用于氢化还原和醛醇环化，作为大环内酯和萘吡喃抗生素的仿生合成。聚酮内酯的合成是从弗雷米自由基氧化开始的。对三环5-6-7元化合物进行彻底的臭氧分解得到稳定的聚酮内酯，通过x射线晶体分析确定其结构为来自的双烯醇。聚酮内酯的硼氢化钠还原得到了8个四醇异构体，它们对应于大环内酯类抗生素的糖苷元。其中三种四醇的相对立体化学也通过x射线分析确定。对聚酮内酯在不同条件下的分子内醛化反应进行了研究，结果表明，用KOAc在MeOH中进行醛化反应得到的主要产物是抗真菌萘比喃的前体——半紫黄质，效果最好。目前，稳定的聚酮内酯已被有效地制备为双烯醇，进一步的仿生衍生是当前研究的主题。

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.