Asymmetric Synthesis of (-)-Colchicine and Its Natural Analog (-)-N-Acetylcolchicine Methyl Ether

(-)-Colchicine and its natural analogue (-)-N-acetylcolchinol methyl ether have been synthesized in a com-paratively conciser asymmetric synthetic approach. Firstly, the carbon framework was constructed by Aldol condensation of simple aldehydes and ketones, and then the chiral amine intermediates were synthesized economically and efficiently through asymmetric reductive amination with chiral tert-butanesulfinamide. The 3-rings skeleton of colchicine and related alkaloids was then constructed by oxidation with hypervalent iodine reagent. Our strategy provides an efficient method for the convenient and economical synthesis of these alkaloids.

Automated summary

(-)-Colchicine and (-)-N-acetylcolchinol methyl ether were synthesized using a concise asymmetric synthetic approach. The carbon framework was constructed through Aldol condensation of simple aldehydes and ketones, followed by the economical and efficient synthesis of chiral amine intermediates through asymmetric reductive amination with chiral tert-butanesulfinamide. The 3-rings skeleton of colchicine and related alkaloids was then constructed by oxidation with hypervalent iodine reagent. This strategy provides an efficient method for the convenient and economical synthesis of these alkaloids.