A new route for the preparation of the 22,23-dioxocholestane side chain from diosgenin and its application to the stereocontrolled construction of the 22R,23S-diol function

Abstract

The new (22R,23S,25R)-3 beta, 16 beta, 26-triacetoxy-cholest-5-ene-22,23-diol (11a) was synthesized from diosgenin (3) through a synthetic route based on chemoselective RuO4 oxidation of (25R)-3 beta,16 beta-diacetoxy-23-ethyl-23(1), 26-epoxycholesta-5,23(23(1))-dien-22-one (9) that afforded (20S,25R)-3 beta,16 beta,26-triacetoxycholest-5-ene-22,23-dione (10) which was stereoselectively reduced using NaBH4. Compound 9 was obtained from the known isomeric 22,26-epoxycholest-5-ene steroidal skeleton 8b by treatment with p-TsOH in toluene, amberlyst-15 or directly from diosgenin by treatment with BF3 center dot OEt2/AC(2)O. Chemoselective reduction of the 23-keto group of 10, was attained using NaBH4/ZnCl2 at - 70 degrees C to give 23S-14. The NMR spectra of all compounds were unambiguously assigned based on one and two dimensional experiments and the C-22 and C-23 stereochemistry in the diacetate derivative 11b, as well as the structure of epoxycholestene 9 were further established by X-ray diffraction analyses. The new route for the functionalization of the side chain of diosgenin can find application in the synthesis of norbrassinosteroid analogues. (c) 2005 Elsevier Ltd. All rights reserved.