Biosynthesis of slaframine, (1S,6S,8aS)-1-acetoxy-6-aminooctahydroindolizine, parasympathomimetic alkaloid of fungal origin. 3. Origin of the pyrrolidine ring

Abstract

The phytopathogen R. leguminicola was previously shown to incorporate pipecolic acid into the piperidine alkaloids 1-acetoxy-6-aminooctahydroindolizine (slaframine) and 3,4,5-trihydroxyoctahydro-1-pyrindine. In the experiments described, resting cultures of R. leguminicola were incubated with [1-14C]- and [2-14C]malonic acid and with [1-14C]- and [2-2H]acetic acid. Both acids were incorporated into the ring systems of both alkaloids. Mass spectrometric analysis of 2H-enriched slaframine showed that the label resides in the 5-membered ring and the methyl carbon of acetate is joined to the carboxyl C of pipecolate. A pipecolate-dependent decarboxylation of [1-14C]malonate was demonstrated in cell-free extracts of R. leguminicola. The results account for previously unattributed C in the 2 alkaloids and suggest the formation of an 8 -C intermediate common to both alkaloids by acylation malonate with pipecolic acid.