Facial synthesis of key intermediate of obeticholic acid via Pd-catalyzed Kumada-Tamao-Corriu cross-coupling reaction

Xiangjie Di; Jie Han; Sheng Zou; Xia Wei; Qingfei Huang; Jin Zhu; Yuanhua Wang; Liu Zhong; Qiwei Wang

doi:10.1016/j.steroids.2020.108657

Facial synthesis of key intermediate of obeticholic acid via Pd-catalyzed Kumada-Tamao-Corriu cross-coupling reaction

Steroids. 2020 Aug:160:108657. doi: 10.1016/j.steroids.2020.108657. Epub 2020 May 18.

Authors

Xiangjie Di¹, Jie Han², Sheng Zou³, Xia Wei², Qingfei Huang⁴, Jin Zhu³, Yuanhua Wang⁵, Liu Zhong⁶, Qiwei Wang⁷

Affiliations

¹ Department of Chemistry, Xihua University, Chengdu 610039, China; Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China; University of Chinese Academy of Sciences, Beijing 100049, China.
² Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China; University of Chinese Academy of Sciences, Beijing 100049, China.
³ Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China.
⁴ Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China. Electronic address: qfhuang@cioc.ac.cn.
⁵ College of Chemistry, Sichuan University, China. Electronic address: yhwang@scu.edu.cn.
⁶ Department of Chemistry, Xihua University, Chengdu 610039, China.
⁷ Department of Chemistry, Xihua University, Chengdu 610039, China; Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China. Electronic address: wqw@cioc.ac.cn.

PMID: 32439409
DOI: 10.1016/j.steroids.2020.108657

Abstract

Obeticholic acid (OCA) is used to treatment for Primary Biliary Cholangitis and other Famesoid X Receptor related diseases. Through the palladium catalyzed Kumada-Tamao-Corriu cross-coupling reaction, a novel and efficient method for synthesis of OCA with satisfied yield was successfully developed. The absolute configuration of the key intermediate was confirmed by Single-crystal X-ray Diffraction. It affords good strategy for large-scale synthesis of OCA.

Keywords: Catalyzed; Cross-coupling reaction; Key intermediate; Obeticholic acid.

MeSH terms

Catalysis
Chenodeoxycholic Acid / analogs & derivatives*
Chenodeoxycholic Acid / chemical synthesis
Chenodeoxycholic Acid / chemistry
Molecular Conformation
Palladium / chemistry*
Stereoisomerism

Substances

obeticholic acid
Chenodeoxycholic Acid
Palladium