1995 Volume 53 Issue 7 Pages 566-580
Starting from isolation and structural determination of mushroom poisons, various chemistry was developed.
1. Isolation, structural determination and synthesis of a cyclohumulanoid, illudin, occurred in Lampteromyces japonicus were performed. Various cyclohumulanoids were chemically derived from humulene modeling after their biosynthesis. The entirely different mode of biosynthetical cyclization of humulene was chemically simulated employing mercuric salts and its reaction mechanism was disclosed. And this condition was used for the biosynthetic like synthesis of prostaglandin E1. Two cyclohumulanoids carrying a shifted methyl group were derived through a newly found “apparent 1, 2-shift” namely “cyclopropane sliding reaction”. The conformation of humulene was studied by molecular mechanics calculations and its four stable conformers were found. The conformational consideration improved biogenesis of cyclohumulanoid. The biosynthetical “conformationally selective cyclization” was chemically simulated. Application of molecular mechanics calculations to natural products was first developed and several findings were obtained.
2. Isolation, structural determination and synthesis of a kainoid, acromelic acids, occurred in Clitocybe acromelalga were achieved. Because of extraordinary potent depolarizing activity, several analogs were synthesized through newly developed various effective routes. The relationship between biological activity and structure or conformation of substrate were studied using synthetic products. The role of the substituent at C4 of the kainoid was considered to transfer electrons to the receptor.
3. Two cyclic polyether isolated from algae were totally synthesized. Of thyrsiferol, the construction of C-ring, a pyran carrying boat conformation, and A-ring, heavily substituted bromopyran, were key steps. Teurilene, a squalene derived meso-polyether with 8 chiral centers; was produced through a few steps using newly found mode of stereoselective oxidation of double bonds. Antivirus virantmycin was synthesized by stereoselective nitrene addition to an intramolecular double bond and its stereochemistry was determined. Grayanotoxin III, a heavily oxygenated four cyclic diterpene, was totally synthesized employing highly stereo-selective SmI2 induced radical coupling in the construction of three rings.
