|Budget Amount *help
¥7,400,000 (Direct Cost : ¥7,400,000)
Fiscal Year 1994 : ¥1,700,000 (Direct Cost : ¥1,700,000)
Fiscal Year 1993 : ¥5,700,000 (Direct Cost : ¥5,700,000)
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.