TOTAL SYNTHESIS OF NATURAL PI-091, A NEW PLATELET-AGGREGATION INHIBITOR OF MICROBIAL ORIGIN

The total synthesis of a new platelet aggregation-inhibiting gamma-lac tam PI-091 (1) gave a 1:1 diastereomeric mixture at the gamma-ketal ca rbon. The high-yielding aldol reaction of an appropriately protected 1 ,3,4-trihydroxy-4-methyldecan-2-one 42, prepared from D-glucose, with the kinetically generated enolate of 3-methyl-2-butanone provided 43. The resulting diastereomeric mixture of the aldol adduct 43 was conver ted to a 2,4-alkylated furan 45 via an intramolecular ketalization fol lowed by dehydration. The addition of a singlet oxygen to the alpha-tr imethylsilylated furan 48 derived from 45 under photochemical conditio ns efficiently provided an alpha,gamma-dialkylated gamma-hydroxy gamma -lactone 47. The transformation of methyl ketal 52 prepared from 47 in to gamma-hydroxy gamma-lactam 53 was achieved by exposure to liquid am monia in MeOH. The total synthesis of 1 was achieved from 52 through t he Dess-Martin periodinane oxidation of the secondary hydroxy group in the side chain. The present total synthesis revealed that the stereog enic carbon center in the side chain in natural 1 is S.