Parallel solid-phase synthesis of a model library of 7 alpha-alkylamide estradiol derivatives as potential estrogen receptor antagonists

The C17-THP derivative of 7 alpha-(11-azidoundecanyl)-estradiol (4) was syn thesized and coupled to an aminomethyl resin via a photolabile o-nitrobenzy l linker. Reduction of the azide by the Staudinger reaction to its correspo nding amine followed by acylation using four activated NFmoc protected amin o acids gave a first level of diversity. Subsequent deprotection of the Fmo c followed by a second acylation with five activated carboxylic acids produ ced, after photocleavage, a model library of twenty antiestrogen-related 7 alpha-alkylamide estradiol derivatives in acceptable overall yields and ver y good purities. (C) 1999 Elsevier Science Ltd. All rights reserved.