3α,7α,14α-三羟基-5β-胆烷-24-酸的合成：脊椎动物中一种潜在的初级胆汁酸。

Synthesis of 3alpha,7alpha,14alpha-trihydroxy-5beta-cholan-24-oic acid: a potential primary bile acid in vertebrates.

作者信息

Kakiyama Genta, Iida Takashi, Goto Takaaki, Mano Nariyasu, Goto Junichi, Nambara Toshio

机构信息

Department of Chemistry, College of Humanities and Sciences, Nihon University, Tokyo, Japan.

出版信息

Chem Pharm Bull (Tokyo). 2004 Mar;52(3):371-4. doi: 10.1248/cpb.52.371.

DOI:10.1248/cpb.52.371

PMID:14993766

Abstract

A method for the synthesis of 3alpha,7alpha,14alpha-trihydroxy-5beta-cholan-24-oic acid which is a possible candidate of bile acid metabolite in vertebrates was developed. The principal reactions involved were 1). stereoselective remote-hydroxylation of methyl ursodeoxycholate diacetate with dimethyldioxirane, 2). site-selective protection at C-3 by tert-butyldimethylsilylation of the resulting 3alpha,7alpha,14alpha-trihydroxy ester, 3). oxidation of the diol with pyridinium dichromate adsorbed on activated alumina, 4). stereoselective reduction of the 7-ketone with zinc borohydride, and 5). cleavage of the protecting group at C-3 with p-toluenesulfonic acid. A facile elimination of the 14alpha-hydroxy group under an acidic or neutral condition is also described. The synthetic reference compound is now available for comparison with unidentified biliary bile acids detected in vertebrate bile.

摘要

开发了一种合成3α,7α,14α-三羟基-5β-胆烷-24-酸的方法，该化合物可能是脊椎动物胆汁酸代谢物的候选物。主要反应包括：1）用二甲基二氧杂环丙烷对熊去氧胆酸二乙酸甲酯进行立体选择性远程羟基化；2）用叔丁基二甲基甲硅烷基对所得的3α,7α,14α-三羟基酯在C-3位进行位点选择性保护；3）用吸附在活性氧化铝上的重铬酸吡啶鎓氧化二醇；4）用硼氢化锌对7-酮进行立体选择性还原；5）用对甲苯磺酸裂解C-3位的保护基团。还描述了在酸性或中性条件下14α-羟基的简便消除。现在可以使用合成参考化合物与在脊椎动物胆汁中检测到的未鉴定胆汁酸进行比较。