Abstract

Microwave-assisted phospha-Michael addition reactions were carried out in the 13α-oestrone series. The exocyclic 16-methylene-17-ketones as α,β-unsaturated ketones were reacted with secondary phosphine oxides as nucleophilic partners. The addition reactions furnished the two tertiary phosphine oxide diastereomers in high yields. The main product was the 16α-isomer. The antiproliferative activities of the newly synthesised organophosphorus compounds against a panel of nine human cancer cell lines were investigated by means of MTT assays. The most potent compound, the diphenylphosphine oxide derivative in the 3-O-methyl-13α-oestrone series (9), exerted selective cell growth-inhibitory activity against UPCI-SCC-131 and T47D cell lines with low micromolar IC₅₀ values. Moreover, it displayed good tumour selectivity property determined against non-cancerous mouse fibroblast cells.

摘要

在13α-雌酮系列中进行了微波辅助的磷-迈克尔加成反应。作为 α,β-不饱和酮的环外 16-亚甲基-17-酮与作为亲核伙伴的仲氧化膦反应。加成反应以高产率提供了两种叔氧化膦非对映异构体。主要产物是16α-异构体。通过 MTT 测定研究了新合成的有机磷化合物对一组九种人类癌细胞系的抗增殖活性。最有效的化合物，3 - O-甲基-13α-雌酮系列中的二苯基氧化膦衍生物( 9 )，对 UPCI-SCC-131 和 T47D 细胞系具有选择性的细胞生长抑制活性，具有低微摩尔 IC ₅₀值。此外，它对非癌性小鼠成纤维细胞显示出良好的肿瘤选择性。