Evans DA,
*,
Tannis SP,
Hart DJ.
California Institute of Technology, Pasadena, USA
A Convergent Total Synthesis of (±)-Colchicine and (±)-Desacetamidoisocolchicine.
J. Am. Chem. Soc. 1981;
103: 5813-5821
DOI:
10.1021/ja00409a032
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.
