（17R）-和（17S）-17-羟基-14,15-断雄甾-4-烯-15-炔-3-酮的合成以及（17S）-非对映异构体的X射线晶体结构

Synthesis of (17R)- and (17S)-17-hydroxy-14, 15-secoandrost-4-en-15-yn-3-one and the X-ray crystal structure of the (17S)-diastereomer.

作者信息

Hu Y, Sherwin P F, Covey D F

机构信息

Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

出版信息

Steroids. 1995 Mar;60(3):250-5. doi: 10.1016/0039-128x(94)00044-d.

DOI:10.1016/0039-128x(94)00044-d

PMID:7792826

Abstract

(17R,S)-17-Hydroxy-14,15-secoandrost-4-en-15-yn-3-one has been shown previously to be a mechanism-based inactivator of rat liver 3 alpha-hydroxysteroid dehydrogenase. This manuscript describes the synthesis of this diastereomeric 14,15-secosteroid from [2S-2 alpha,4a alpha,4b beta,10a beta)]- 1,2,3,4a,4b,7,9,10,10a-decahydro-2,4b-dimethyl-7-oxo-2-phenanth renecarboxylic acid methyl ester. The separation of this diastereomeric 14,15-secosteroid into (17R)- and (17S)-17-hydroxy-14,15-secoandrost-4-en-15-yn-3-one was accomplished by HPLC separation of the (S)-1-[(4-methylphenyl)sulphonyl]-2-pyrrolidinecarboxylate derivatives on a silica column. The crystal structure of (17S)-17-hydroxy-14,15-secoandrost-4-en-15-yn-3-one was then solved by X-ray diffraction analysis to establish unambiguously the absolute configuration of the diastereomeric 14,15-secosteroid.

摘要

(17R,S)-17-羟基-14,15-断雄甾-4-烯-15-炔-3-酮先前已被证明是大鼠肝脏3α-羟基类固醇脱氢酶的一种基于机制的失活剂。本论文描述了由[2S-2α,4aα,4bβ,10aβ)]-1,2,3,4a,4b,7,9,10,10a-十氢-2,4b-二甲基-7-氧代-2-菲羧酸甲酯合成这种非对映体14,15-断甾体。通过在硅胶柱上对(S)-1-[(4-甲基苯基)磺酰基]-2-吡咯烷羧酸酯衍生物进行高效液相色谱分离，将这种非对映体14,15-断甾体分离为(17R)-和(17S)-17-羟基-14,15-断雄甾-4-烯-15-炔-3-酮。然后通过X射线衍射分析解析了(17S)-17-羟基-14,15-断雄甾-4-烯-15-炔-3-酮的晶体结构，以明确确定该非对映体14,15-断甾体的绝对构型。