Epimerisation of allylic alcohols

Abstract

The present invention relates to processes for epimerising alcohols of compounds having a hydroxyl substituent on an asymmetric allylic carbon, such as compounds useful for the synthesis of vitamin D analogues where the epimeric hydroxyl substituent is at the 24 position. The invention further relates to methods of producing intermediates useful for the synthesis of calcipotriol by said epimerisation processes.

Description

field of invention The present invention relates to a novel method of epimerization of compounds, such as those useful in the synthesis of vitamin D analogues, which have a hydroxyl substituent on an asymmetric allylic carbon, for example at position 24. The present invention further relates to the application of the intermediate produced by this method in the preparation of calcipotriol i.e. {(5Z, 7E, 22E, 24S)-24-cyclopropyl-9,10-broken cholesterol-5,7,10(19 ), 22-tetraene-1α-3β-24-triol} or calcipotriol monohydrate. Background of the invention Calcipotriol (Structure I) [CAS 112965-21-6] shows strong activity in inhibiting undesirable proliferation of epidermal keratinocytes [F.A.C.M. Castelijins, M.J. Gerritsen, I.M.J.J.van Vlijmen-Willems, P.J. van Erp, P.C.M. van de Kerkhof; Acta Derm. Venereol. 79, 11, 1999]. The efficacy of calcipotriol and monohydrate (I-hydrate) calcipotriol in the treatment of psoriasis has been shown in many clinical trials [D.M.Ashcroft et al...

AI Technical Summary

Problems solved by technology

This epimerization process has the disadvantage that it involves two additional chemical transformations, esterification and saponification of IIIb, making the process economically unfavorable, especially on an industrial scale

WO94 / 07853 discloses various vitamin D analogs having a hydroxyl substituent on the asymmetric allyl carbon at position 24, but does not disclose a method for epimerizing the alcohol

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