Optimization and Impurity Control Strategy for Lithocholic Acid Production Using Commercially Plant-Sourced Bisnoralcohol

Chunling Zeng; Shitang Xu; Zhenlong Yin; Yue Cui; Xinhua Xu; Ningbo Li

doi:10.1021/acsomega.3c02548

Optimization and Impurity Control Strategy for Lithocholic Acid Production Using Commercially Plant-Sourced Bisnoralcohol

ACS Omega. 2023 Jun 14;8(25):23130-23141. doi: 10.1021/acsomega.3c02548. eCollection 2023 Jun 27.

Authors

Chunling Zeng¹, Shitang Xu¹, Zhenlong Yin¹, Yue Cui¹, Xinhua Xu¹, Ningbo Li²

Affiliations

¹ College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.
² School of Basic Medical Sciences, Shanxi Medical University, Taiyuan 030001, China.

Abstract

In this study, lithocholic acid (LCA) was prepared using commercially available plant-sourced bisnoralcohol (BA), and the overall yield of the product was 70.6% for five steps. To prevent process-related impurities, the isomerizations of catalytic hydrogenation in the C4-C5 double bond and reduction of the 3-keto group were optimized. The double bond reduction isomerization was improved (5β-H:5α-H = 97:3) using palladium-copper nanowires (Pd-Cu NWs) instead of Pd/C. The reduction of the 3-keto group was 100% converted to a 3α-OH product by 3α-hydroxysteroid dehydrogenase/carbonyl reductase catalysis. Moreover, the impurities during the optimization process were comprehensively studied. Compared with the reported synthesis methods, our developed method significantly improved the isomer ratio and overall yield, affording ICH-grade quality of LCA, and it is more cost-effective and suitable for large-scale production of LCA.