Epimerization of analogs of vitamin d

C - Chemistry – Metallurgy – 07 – C

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C07C 401/00 (2006.01)

Patent

CA 2489593

Provided is a method of general applicability of epimerizing a vitamin-D analog having an asymmetric allylic carbon atom at the C-24 position, which comprises the steps of: a) esterifying the hydroxyl group on the asymmetric allylic carbon atom at the 24 position with an esterifying agent, b) contacting a solution of the ester in a solvent with an epimerization-active solid, whereby the ester is epimerized, and c) hydrolysing the epimerized ester to obtain a mixture of C-24 epimers having a hydroxyl substituent on the asymmetric allylic carbon at position 24. The method is of particular utility in making calcipotriene.

L'invention concerne une méthode d'applicabilité générale d'épimérisation d'un analogue de la vitamine D présentant un atome de carbone allylique asymétrique, en position C-24. Cette méthode comprend les étapes consistant à : a) estérifier le groupe hydroxyle sur l'atome de carbone allylique asymétrique situé en position 24, à l'aide d'un agent d'estérification, b) mettre en contact une solution de l'ester dans un solvant et un solide actif d'épimérisation, l'ester étant épimérisé, et c) hydrolyser l'ester épimérisé, pour obtenir un mélange d'épimères C-24, présentant un substituant hydroxyle sur le carbone allylique asymétrique situé en position 24. Cette méthode est particulièrement utile pour fabriquer du calcipotriène.

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