Synthesis of (±)-Vilmoraconitine

Key words

(±)-vilmoraconitine - norditerpenoid alkaloid - cyclopropane - oxidative dearomatization - intramolecular Diels–Alder cycloaddition - Mannich reaction

Significance

Liu, Qin, and co-workers report the first total synthesis of (±)-vilmoraconitine, a norditerpenoid alkaloid isolated in 2008 from Aconitum vilmorinianum. Vilmoraconitine was the first aconitine-type alkaloid reported with a heptacyclic framework incorporating a congested cyclopropane. The aconitines and their synthetic analogues display significant anti-inflammatory, analgesic, and cardioactive effects.

Comment

Oxidative dearomatization/Diels–Alder cycloaddition sequence of phenol B quickly assembled ketone D. Ozonolytic cleavage of the resulting alkene in E followed by fragmentation led to aldehyde G. Mannich reaction in presence of TFA forged tetracycle H in a single step. After oxidation of J, silyl enol ether formation and intramolecular Diels−Alder reaction installed the congested cyclopropane in L and completed the heptacyclic framework of (±)-vilmoraconitine.

Publication History

Article published online:
14 April 2023