Enantioselective Total Synthesis of FR900482.

Abstract

The development of two approaches for the enantioselective total synthesis of FR900482 is described. A precursor for the formation of the benzazocine ring was assembled effectively by a modification of the Sonogashira coupling of an aryl triflate with a chiral acetylene unit derived from tartaric acid and the subsequent novel ketone formation via conjugate addition of pyrrolidine to the o-nitrophenylacetylene derivative. The first-generation approach to the key pentacyclic intermediate of our racemic total synthesis utilizes an intramolecular Mitsunobu reaction of an ω-hydroxynitrobenzenesulfonamide to form the benzazocine ring and a stepwise sequence to construct the hydroxymethyl group at the C(7) position. The key intermediate could be synthesized in optically pure form via formation of the characteristic hydroxylamine hemiacetal and a stereoselective epoxide formation. In the second-generation approach, the N-hydroxybenzazocine ring could be constructed directly from an ω-formylnitrobenzene derivative...