Cycloartenol to Buxus alkaloids

Abstract

Cycloartenol, a pentacyclic triterpene alcohol, has emerged as an obligatory intermediate in the biosynthesis of sterols in higher plants and algae. Cycloartenol has also been implicated in the biosynthesis of steroidal alkaloids. The Buxus alkaloids, which have a pregnane-type framework, are considered to arise from cycloartenol by catabolic processes with nitrogen incorporation at an appropriate stage, although no biosynthetic studies appear to have been carried out. Thus, cycloartenol is an important substrate in nature for elaborating a rather large group of secondary metabolites. In an effort to mimic some of these processes in the laboratory, we have carried out transformations of cycloartenol into Buxus alkaloids. New routes for side-chain degradation of cycloartenol and cyclolaudenol have been developed. A novel method for functionalization at C-16 has been worked out and a new strategy for regioselective oxygenation of 4-methyl has been exploited. Synthesis of buxandonine, cycloprotobuxine-F, cycloprotobuxine-A, cyclobuxophyllinine-M and 31-norcyclolaudenone have been achieved.