Synthesis and tubulin-binding properties of new allocolchicinoids.

Allocolchicinoids with B- and C-ring variations were synthesized using sequential enyne-metathesis/ Diels-Alder reactions (A-->AB-->ABC approach) and evaluated for their inhibitory effect on tubulin assembly in vitro. (-)-Allocolchicine 11 with methyl ester at C10 and (+/-)-cyclopropyl allocolchicinoid 32 exhibit similar activity than (-)-colchicine (1), probably derived from a similar flexibility in the biphenyl system. The presence of methyl ester at C10 led to a little loss in potency in comparison with the series with methyl ester at C9. A complete loss of activity was observed for allocolchicine 9 with methyl ester at C11. Copyright 2010 Elsevier Inc. All rights reserved.