一种合成α-鼠胆酸的新方法

A New Method for the Synthesis of α-Muricholic Acid

以猪去氧胆酸为原料,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,其结构经1HNMR、13CNMR、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收率的影响和工艺的稳定性;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的影响,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),同时考察了IBX与中间体Ⅱ的物料比对中间体Ⅲ收率的影响及工艺的稳定性。结果表明:浓盐酸作为催化剂,中间体Ⅱ的收率约99%;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%;获得了中间体Ⅲ的X射线单晶结构,确定了其绝对构型。

Muricholic acid was synthesized from hyodeoxycholic acid via esterification,selective C-6 oxidation,C-7 hydroxylation,C-6 carbonyl reduction and hydrolysis reactions.The resulting product was confirmed by 1HNMR,13CNMR and HRMS.The overall yield of product from hyodeoxycholic acid was 28.9%±0.3%.The effect of different catalysts on the yield of intermediateⅡwas investigated as well as the process stability of esterification was tested.Different oxidants for the selective oxidation of C-3 or C-6 hydroxyl group in intermediateⅡwere screened.2-Iodoxybenzoic acid(IBX)was approved to be good candidate in selective oxidation of the C-6 hydroxyl group.The effect of molar ratio ofⅡto IBX on the yield of intermediateⅢwas studied and the process stability of the reaction was explored.The results showed that the yield of intermediateⅡwas 99%when concentrated HCl was used as catalyst.The yield of intermediateⅢwas up to 82.3%when the molar ratio ofⅡto IBX was 1:1.20.The absolute configuration of intermediateⅢwas determined by single-crystal X-ray diffraction and it was as expected.