MOE Joint International Research Laboratory of Synthetic Biology and Medicine, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, PR China.
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, PR China.
Steroids. 2020 May;157:108594. doi: 10.1016/j.steroids.2020.108594. Epub 2020 Feb 15.
Five cholic acid derivatives (including allo-ω-muricholic acid and CDCA) were synthesized from hyodeoxycholic acid via selective oxidation of C3- or C6-hydroxyl groups by IBX and NBS oxidants and stereocontrolled conversion. The hydroxyl group could be introduced through hydrolyzing α-Br keto with KCO aqueous solution or through oxidizing the double bond by monoperoxyphthalic acid. The reduction of C6-O6 carbonyl to methylene could undergo with PTSH, NaBHCN and ZnCl only at 5β configuration. A feasible synthetic route of CDCA from HDCA has been established to avoid the epimerization with the yield of 45% (8 steps). These strategies provided good yields, stereoselectivity and reproducibility for the preparation of cholic acid derivates and CDCA.
从猪去氧胆酸经选择性氧化 C3-或 C6-羟基，利用 IBX 和 NBS 氧化剂和立体控制转化，合成了 5 种胆酸衍生物（包括 allo-ω-猪去氧胆酸和 CDCA）。羟基可通过水解 α-Br 酮与 KCO 水溶液引入，也可通过过氧邻苯二甲酸氧化双键引入。只有在 5β 构型下，用 PTSH、NaBHCN 和 ZnCl 才能将 C6-O6 羰基还原为亚甲基。建立了从 HDCA 到 CDCA 的可行合成路线，避免了差向异构化，收率为 45%（8 步）。这些策略为制备胆酸衍生物和 CDCA 提供了良好的产率、立体选择性和重现性。
