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、四环素类和硫代吡喃类，都是由聚酮链(β-聚氧烷酸酯)生物化学合成的。在聚酮链的合成研究上投入了大量的化学努力，这是最近一次全面综述的主题。以天然大环内酯苷元为原料，合成了一种环状聚酮(聚酮内酯)。本文首次报道了一种稳定的14元聚酮内酯的合成和X-射线分析，该化合物将进行氢化物还原和羟醛缩合反应，作为大环内酯类和萘并吡喃类抗生素的仿生合成。三环5-6-7元化合物经彻底臭氧化得到稳定的聚酮内酯，其结构经X-射线晶体分析确定为双烯醇类化合物。聚酮内酯的硼氢化钠还原得到8个四醇异构体，与大环内酯类抗生素的苷元相对应。通过X-射线衍射仪测定了其中三个四元醇的相对立体化学结构，并对聚酮内酯在不同条件下的分子内缩醛反应进行了分析，其中以KOAc在甲醇中的使用效果最好，得到了一种主要的产物，即抗真菌萘并吡喃的递归产物--半氧口恶辛。由于已经有效地得到了稳定的聚酮内酯作为二烯醇，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.