State Key Laboratory of Chemical Oncogenomics and Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen 518055, China.
Green Catalysis Center and College of Chemistry, Zhengzhou University, 100 Science Avenue, Zhengzhou, Henan 450001, P. R. China.
Org Lett. 2021 May 7;23(9):3421-3425. doi: 10.1021/acs.orglett.1c00881. Epub 2021 Apr 12.
The non-immune-suppressive cyclophilin inhibitor CRV431 is a clinical candidate to cure nonalcoholic steatohepatitis (NASH) and has the potential to treat liver fibrosis and cancer incidence. Herein we report a concise chemical semisynthesis of CRV431 in four steps from the commercially available cyclosporine, featuring in this the flow-chemistry-based methylenation an intermolecular ring-closing metathesis and a Rh-catalyzed diastereoselective hydrogenation.
非免疫抑制性环孢素抑制剂 CRV431 是一种治疗非酒精性脂肪性肝炎（NASH）的临床候选药物，具有治疗肝纤维化和癌症发病率的潜力。本文报道了从商业可得的环孢菌素经四步简洁化学半合成 CRV431 的方法，其特征在于基于流动化学的亚甲基化、分子间的环 closing metathesis 和 Rh 催化的非对映选择性氢化。
