| Abstract
| - Six new calcitriol analogues, conformationally restricted at their side chain by the introduction of botha cyclopropane ring at C17−C20 and a double or triple bond at C22, were synthesized using the Wittig−Horner approach to construct the triene system. The six CD-ring and side-chain bearing fragments wereprepared from ketone 14 by a divergent route to generate both series of epimers at C20, followed bystereoselective cyclopropanation. The (E)-alkenyl side chain was synthesized by means of a Wittig reaction.The alkynyl side chain was prepared by Corey−Fuchs homologation, followed by alkylation. The (Z)-alkenyl side chain was prepared from the previous alkyne by partial hydrogenation. The 20-epi analoguesbind more strongly to VDR than the corresponding analogues with the C20 natural stereochemistry.These results can be reasoned by conformational analysis and hydrophobic interactions with the VDRligand-binding domain.
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