Stereochemical Studies. LIV. A Biogenetic-type Asymmetric Synthesis of optically Active Galanthamine from L-Tyrosine

Abstract

A biogenetic-type asymmetric synthesis of optically active galanthamine ((+)-4 and (-)-4) is described. Norbelladine derivative (10), having C₂ symmetry in the aromatic moiety of C₆-C₁-N part, was prepared from L-tyrosine, and was converted to narwedinetype enone (11) by oxidation and highly specific asymmetric cyclization. Phosphorylation of phenolic hydroxyl group followed by sodium borohydride reduction afforded 14 having galanthamine skeleton. N-Methylation followed by removal of the methoxycarbonyl and phosphate moieties afforded (+)-galanthamine ((+)-4). Formal total synthesis of (-)-galanthamine ((-)-4) from L-tyrosine via enantiomeric interconversion of narwedine derivative (12) is also described.