A novel synthesis of colchicide and analogues from thiocolchicine and congeners: reevaluation of colchicide as a potential antitumor agent.
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.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000627:therapeutic use; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism
D000970:Antineoplastic Agents; D014404:Tubulin; C014856:thiocholchicine; D003078:Colchicine