The structure of 2-methoxy-5-(2′,3′,4′-trimethoxyphenyl)tropone, an effective analog of colchicine

Abstract

2-Methoxy-5-(2′,3′,4′-trimethoxyphenyl)tropone is an active analog of colchicine, a mitotic spindle inhibitor, which is missing the middle “B” ring. This compound crystallizes in the triclinic system, space group P 1 ̄ , with Z = 2; a = 10.135(2), b = 10.166(4), and c = 7.863(2) Å; α = 82.15(3), β = 103.49(3), and γ = 107.16(2)∘; and V = 750.7(4) Å 3. The structure was solved by direct methods and refined by full-matrix least-squares to a final R = 0.063, using 2503 observed reflections and 271 parameters. Despite the absence of the middle ring, the conformation of the molecule is similar to that of colchicine, isocolchicine, and their derivatives. The troponoid ring is dissimilar to the phenyl ring in that it is not aromatic and does have alternating short and long bond lengths. The dihedral angle between the least-squares planes of the two rings is −57.4∘. Van der Waals surface representations of the analog and colchicine are presented to demonstrate the similarity and differences of these two molecules. The structural information of the analog is consistent with the interpretation of thermodynamic parameters which govern the interactions between brain tubulin and the analog.