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

• Published in: Steroids 2018-06, Vol.134, p.67-77
• Main Authors: Kiss, Anita, Mernyák, Erzsébet, Wölfling, János, Sinka, Izabella, Zupkó, István, Schneider, Gyula
• Format: Article
• Language: English
• Subjects: 13α-Estrone; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative activity; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry Techniques, Synthetic; Humans; Stereocontrolled synthesis; Stereoisomerism; Stereoisomers; Trientine - chemical synthesis; Trientine - chemistry; Trientine - pharmacology
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2018.02.008

[Display omitted] •Stereoselective synthesis of diastereomeric diols.•Straightforward synthetic route from trans- to cis-diols.•Substantial antiproliferative action against HeLa. 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.