A Novel Synthesis of Colchicide and Analogues from Thiocolchicine and Congeners: Reevaluation of Colchicide as a Potential Antitumor Agent

Article abstract of DOI:10.1021/jm00387a028

Desulfurization of thiocolchicine with Raney nickel in a hydrogen atmosphere yielded tetrahydromethoxycolchicine (2), which was readily separated from unreacted thiocolchicine by chromatography and was smoothly oxidized to 10-demethoxycolchicine (colchicide) by Pd/C in refluxing toluene.Several analogues of colchicide were prepared from the corresponding thiocolchicines by this procedure.Treatment of colchicide with concentrated sulfuric acid yielded 2-demethylcolchicide.Colchicide and its analogues were found to be inactive in a tubulin-binding assay.Evidence is presented that colchicide prepared earlier from thiocolchicine with Raney nickel in aerial atmosphere was contamination with 1-2percent thiocolchicine.