Total Synthesis of (±)-Desacetylcolchicine and Formal Synthesis of (±)-Colchicine

Key words

(±)-colchicine - Corey–Chaykovsky cyclopropanation - Curtius rearrangement

Significance

In 1981, Evans and co-workers reported the total synthesis of colchicine, a natural product that attracted the interest of chemists for decades. Their route featured a highly convergent approach, giving quick access to the tropolone scaffold present in colchicine. The approach furthermore solved the problem of introducing the amido side chain via a Curtius rearrangement.

Comment

Saturated ester D and ketal G are coupled via an aldol reaction to yield aldol adduct H as a 1:1 mixture of diastereomers. Acid-induced spirocyclization followed by in situ rearrangement yielded the desired tropolone J, from which (±)-des­acetylcolchicine was accessible by a Curtius rearrangement.

Publication History

Article published online:
17 June 2021