通过 BF3 促进的 6β-羟基-5,19-环甾体的重排/取代反应合成 B 环修饰的甾体。

Synthesis of B-ring-modified steroids through BF3-promoted rearrangement/substitution of 6β-hydroxy-5,19-cyclosteroids.

机构信息

Department of Chemistry, University of Cologne , Greinstr. 4, 50939 Köln, Germany.

出版信息

Org Lett. 2012 Jul 20;14(14):3692-5. doi: 10.1021/ol301532w. Epub 2012 Jul 5.

Abstract

The BF3·Et2O-promoted reaction of 3β-acetoxy-5,19-cyclo-pregnan-6β-ol-20-one with different nucleophiles was investigated. B-homo steroids (3β-acetoxy-B-homo-6a-β-alkoxy-pregna-5(10)-en-20-ones) were obtained with primary and secondary alcohols, while the reaction with common carboxylic acids selectively afforded the corresponding 3β-acetoxy-6β-(acyloxymethyl)-pregna-5(10)-en-20-ones. The transformations are supposed to proceed via the rearrangement of a cyclopropyl-methyl cation (bicyclobutonium) intermediate, which is regioselectively opened in dependence on the nucleophile employed. The method represents an efficient, diversity-oriented entry to new B-ring-modified steroids, which are of potential pharmaceutical relevance.

摘要

BF3·Et2O 促进的 3β-乙酰氧基-5,19-环孕甾烷-6β-醇-20-酮与不同亲核试剂的反应进行了研究。伯醇和仲醇与该化合物反应生成 B-同型甾体（3β-乙酰氧基-B-同型-6a-β-烷氧基-孕甾烷-5(10)-烯-20-酮），而与常见羧酸的反应则选择性地得到相应的 3β-乙酰氧基-6β-（烷氧羰甲基）-孕甾烷-5(10)-烯-20-酮。这些转化被认为是通过环丙基甲基阳离子（双环丁鎓）中间体的重排进行的，该中间体根据所使用的亲核试剂进行区域选择性开环。该方法代表了一种高效、多样化的新型 B 环修饰甾体的合成方法，这些甾体具有潜在的药物相关性。