Cryptopleurine, a synthesis based on biogenetic considerations

Abstract

A ten-stage synthesis of (±)-cryptopleurine is described. In line with biogenetic postulates it involves oxidative coupling of 2-(3,4-dihydroxyphenyl)-cis-3-(4-hydroxyphenyl)quinolizidin-4-one (VII; R¹= H, R²= O), itself obtained in six steps from 2-methylpyridine, methyl 3,4-dimethoxybenzoate, and 4-methoxyphenylacetyl chloride. The resulting dienone was found to have undergone dehydrogenation and, after rearrangement with acid, methylation, and reduction, afforded the alkaloid (I; R¹= R²= R³= H; n= 2).