Conformational Analysis of Colchicine and Isocolchicine by Molecular Mechanics
The structures of isocolchicine (3) and colchicine (1) have been calculated using the MMX routine. The low energy conformations for isocolchicine and colchicine fit well with x-ray crystallographic data. The B ring atropisomer of isocolchicine, which can be spectroscopically observed, is calculated to be <1 kcalmole higher in energy than 3. The boat-boat inversion conformer of colchicine, which has been predicted to be important in the binding of 1 to tubulin, is also calculated. The B ring geometry of this isomer does not differ to the extent previously predicted.