A novel synthesis of colchicide and analogs from thiocolchicine and congeners: reevaluation of colchicide as a potential antitumor agent

Journal of Medicinal Chemistry
1987.0

Abstract

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 nicel in aerial atmosphere was contamination with 1-2% thiocolchicine.

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