Ji J,
Chen J,
Qin S,
Li W,
Zhao J,
Li G,
Song H,
Liu X.-Y,
Qin Y.
*
Sichuan University, Chengdu, P. R. of China
Total Synthesis of Vilmoraconitine.
J. Am. Chem. Soc. 2023;
145: 3903-3908
DOI:
10.1021/jacs.3c00318
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.
