Synthesis of allocolchicinoids: a 50 year journey

Published data on the stereo- and enantioselective synthesis of allocolchicinoids, which are of interest as antitumour agents, are summarized. The stereochemical features of these compounds are described. Two key approaches to their preparation are considered, namely, the synthesis from natural colchicine and total synthesis from commercially available reagents. Various total syntheses of N-acetylcolchinol are performed using biaryl oxidative and reductive coupling, cyclopropanation–ring expansion and Nicholas reaction. The synthetic routes to allocolchicine are based on Diels–Alder cycloaddition, combination of Diels–Alder and metathesis reactions and direct catalytic CH-arylation. Analogues of the colchicine site ligands incorporating heteroaromatic rings are briefly considered; their structural features and methods of synthesis are discussed. Bibliography — 144 references.