Conformational Analysis of Colchicinoids Containing an Electron-Deficient Aromatic Ring on the B Ring

A dinitrophenyl substituent at the C-7 position of N-deacetylcolchicine and N-deacetylisocolchicine was shown to perturb the ¹H NMR and circular dichroic spectra of colchicinoid ring systems. The perturbations were explained by an interaction between the C-7 substituent and the A and/or C rings. Other aromatic substituents or large substituents located at the C-7 position (J. Med. Chem. 1983, 26, 1365) have not been reported to influence the aS-aR equilibrium of the phenyltropone ring junction. It was concluded that the sterically unfavored atropisomers were stabilized by the interaction of an electron-deficient ring with the more electron-rich A ring of the colchicinoid molecules.