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

Abstract

The C17-THP derivative of 7α-(11-azidoundecanyl)-estradiol ( 4) was synthesized and coupled to an aminomethyl resin via a photolabile o-nitrobenzyl linker. Reduction of the azide by the Staudinger reaction to its corresponding amine followed by acylation using four activated NFmoc protected amino acids gave a first level of diversity. Subsequent deprotection of the Fmoc followed by a second acylation with five activated carboxylic acids produced, after photocleavage, a model library of twenty antiestrogen-related 7α-alkylamide estradiol derivatives in acceptable overall yields and very good purities.