The synthesis and in vitro activity of some Delta(7,9(11))-lanostadienes

Abstract

The synthesis of Delta(7,9(11))-lanostadiene derivatives functionalized at C(32) starting from 3 beta-acetoxy-7 alpha,32-epoxylanostan-11-one has been presented. The Delta(7,9(11)) moiety was efficiently introduced in three steps in 71% yield by the regioselective abstraction of allylic 8 beta hydrogen. The formyl group of the key intermediate, 3 beta-benzoyloxylanosta-7,9(11)-dien-32-al, has been stereoselectively alkylated into (32S) derivative, whereas its oxidation unexpectedly afforded 3 beta-benxoyloxy-7-oxolanost-8-ene-32,11 alpha-lactone and not the corresponding acid. Delta(7,9(11))-lanostadienes possessing HC(32)=O, C(32)=N, HC(32S)CH3OH, H2C(32)OH, as well as some 11-keto lanostenes, were tested in vitro against several purified cholesterogenic enzymes showing moderate activity, with most the active aldehyde 16 having IC50 = 86 mu M. (C) 1997 by Elsevier Science, Inc.