一种合成α-鼠胆酸的新方法

A new method for the synthesis of a-muricholic acid

摘要:

猪去氧胆酸为原料，经酯化、C-6位选择性氧化、C-7位羟基化、C-6位羰基还原和水解等步骤合成α-鼠胆酸，结构经1H-NMR、13C-NMR、HRMS确认，反应总收率达到28.9±0.3%。考察了催化剂对中间体Ⅱ收率的影响和工艺稳定性；探索了不同氧化剂对中间体Ⅱ中C-3和C-6位羟基氧化的选择性及收率，筛选到可高效选择性氧化C-6位羟基的氧化剂2-碘酰基苯甲酸（IBX），及其与中间体Ⅱ的物料比对中间体Ⅲ收率的影响及工艺稳定性。研究结果表明，1） 浓盐酸作为催化剂，中间体Ⅱ的收率达到99.0%；2）IBX可以选择性氧化中间体Ⅱ中C-6位羟基，且当n（中间体Ⅱ）: n（IBX）=1: 1.20时，中间体Ⅲ的收率达到82.3%；3) 获得了中间体Ⅲ的X-射线单晶结构，确定了其绝对构型。

Abstract:

α-Muricholic acid was synthesized from hyodeoxycholic acid via esterification, selective oxidation, hy-droxylation of C-7 methylene, carbonyl reduction at C-6 and hydrolysis reactions. The resulting product was finally confirmed by 1H-NMR, 13C-NMR and HRMS. The overall yield from hyodeoxycholic acid was calculated to be 28.9±0.3%. The effect of catalysts on the yield of intermediateⅡand the process stability of the esterification reaction was investigated. The oxidants on the selective oxidation of C-3 or C-6 hy-droxyl group in intermediate Ⅱ were screened, and 2-iodobenzoic acid (IBX) was approved to be good candidate in selective oxidation of the C-6 hydroxyl group in intermediate Ⅱ. The effects of the molecu-lar ratio of Ⅱ to IBX on the yield of intermediate Ⅲ and the process stability under the conditions were explored, and the results were as follow: 1) the yield of intermediate Ⅱ was 99.0% by using concentrated HCl as the catalyst; 2) IBX could selectively oxidize hydroxyl group at C-6 of intermediate Ⅱ and the yield of the intermediate Ⅲ was 82.3% when the ratio of n (Ⅱ): n (IBX) was 1: 1.20; 3) the single crystal structure of intermediate Ⅲ was determined, and its absolute configuration was as expected.