Stereoselective synthesis of the four 16-hydroxymethyl-3-methoxy- and 16-hydroxymethyl-3-benzyloxy-13α-estra-1,3,5(10)-trien-17-ol isomers and their antiproliferative activities.

• 影响指数: 2.76
• 发表时间: 06 2018
• 来源期刊: Steroids
• DOI: 10.1016/j.steroids.2018.02.008
• PMID: 29501755
• 文章类型: Journal Article
• 中科院分区: Q3
• 方向: 医学
• 作者列表: Kiss A,Mernyák E,Wölfling J,Sinka I,Zupkó I,Schneider G

关键词: 13α-Estrone; Antiproliferative activity; Stereocontrolled synthesis; Stereoisomers

Mesh: Antineoplastic Agents / chemical synthesis chemistry pharmacology; Cell Line, Tumor; Cell Proliferation / drug effects; Chemistry Techniques, Synthetic; Humans; Stereoisomerism; Trientine / chemical synthesis chemistry pharmacology

Abstract

The reduction of 16-hydroxymethylene-3-methoxy-13α-estra-1,3,5(10)-trien-17-one (14) and 16-hydroxymethylene-3-benzyloxy-13α-estra-1,3,5(10)-trien-17-one (16) yielded a mixture of two diastereomeric diols, the 16α-hydroxymethyl,17β-hydroxy and 16β-hydroxymethyl,17α-hydroxy isomers (17a-20a) in a ratio of 6:1. We describe a straightforward synthetic route to transform the isomers with trans functional groups attached to ring D (17a-20a) into isomers with cis functional groups (25a-28a). We determined the in vitro antiproliferative activities of compounds 17a-20a and 25a-28a by means of MTT assays against a panel of human adherent cancer cell lines HeLa, A2780, MCF-7, T47D, MDA-MB-231 and MDA-MB-361.