An asymmetric route to the demethoxy-fumitremorgins

Abstract

By use of a modified Pictet–Spengler reaction under conditions of kinetic control, the optically pure cis-1,3-disubstituted tetrahydro-β-carboline 21a was prepared from L-tryptophan; this generated a key tricyclic unit that possessed the correct relative and absolute stereochemistry for transformation into demethoxy derivatives of the fumitremorgin mycotoxins. In particular, we converted 21a into the pentacyclic ketone 29, whose structure was confirmed by X-ray crystallography; and 29 was further transformed into demethoxy-fumitremorgin C 1b, whose NMR data matched that of the natural product 1a extremely closely. Our methodology also gives access to a range of analogues of the fumitremorgins.