Total Synthesis of (+)-Heilonine

Key words

(+)-heilonine - steroidal alkaloids - Diels–Alder reaction - Seyferth–Gilbert homologation - Robinson annulation - [2+2+2] cyclization

Significance

(+)-Heilonine is a steroidal alkaloid that was isolated in 1989 from Fritillaria ussuriensisMaxim. It is a member of the cevanine alkaloids, of which only one has been synthesized prior to this work. (+)-Heilonine consists of a hexacyclic framework, including a quinolizidine.

Comment

Ester D is accessed in enantiomerically enriched form via an asymmetric Diels–Alder reaction, and rapidly elaborated into ketone G. Ketone G was subjected to a Robinson annulation, yielding enone H. Lactam L, accessible via an Evans-aldol stratey, was alkylated with propargyl bromide K, giving triyne M. The key rhodium-catalyzed cyclotrimerization of M yielded arene N with the scaffold of the natural product. Few steps remained to access the natural product (+)-heilonine.

Publication History

Article published online:
17 November 2021