A proposal for biosynthesis of the Daphniphyllum alkaloids

Abstract

A hypothesis has been formulated (Scheme 1) for biosynthesis of the pentacyclic, nitrogen-containing moiety of the Daphniphyllum alkaloid secodaphniphylline. The proposal starts with the squalene-derived dialdehyde 7 and employs pyridoxamine to introduce nitrogen and allow formation of the key cyclopentane ring by a variant of the enamine Michael reaction. Key steps in the proposal are the intramolecular Diels-Alder reaction of the hypothetical azadiene 12, leading to imine 13, and Mannich-type closure of the latter substance, giving the secodaphniphylline skeleton. Scheme 2 summarizes a proposed pyridoxal-mediated transformation of homosecodaphniphyllic acid (15) to unsaturated amino acid 19, a skeletal type related to daphnilactone B and yuzurimine. Scheme 2 also suggests reactions whereby the key intermediate 19 might be transformed into daphnilactone A and homodaphniphyllic acid. As shown in Scheme 3, intermediate 13 might give rise to daphnigracine-type alkaloids. Finally, we present synthetic evidence (Scheme 5) in support of the proposed intramolecular Diels-Alder reaction. © 1989 IUPAC