Document Report Card

ID: ALA1121793

Journal: J Med Chem

Title: Biological effects of modified colchicines. Improved preparation of 2-demethylcolchicine, 3-demethylcolchicine, and (+)-colchicine and reassignment of the position of the double bond in dehydro-7-deacetamidocolchicines.

Authors: Rösner M, Capraro HG, Jacobson AE, Atwell L, Brossi A, Iorio MA, Williams TH, Sik RH, Chignell CF.

Abstract: A variety of colchicine, demecolcine, and isocolchicine derivatives were examined for their potency in the lymphocytic leukemia P388 screen in mice, for their toxicity in mice, and for their binding to microtubule protein. A qualitatively direct correlation was found between in vivo potency and toxicity; potency appeared to be less well correlated with tubulin binding. The most potent compounds were N-acylated analogues of colchicine and demecolcine. Among the monophenols, only 3-demethylcolchicine showed an appreciable effect in vitro and in vivo and was less toxic than colchicine. Improved methods were found for the preparation of 3- and 2-demethylcolchicine, which involved the use of 85% phosphoric acid and concentrated sulfuric acid, respectively. Decoupling experiments with 1H NMR proved that the double bond of dehydro-7-deacetamidocolchiceine and its derived tropolonic methyl ethers 24 and 25 was in the 5,6 position, rather than the 6,7 position formerly tentatively assigned.

CiteXplore: 7265112

DOI: 10.1021/jm00135a005