| Institution: | 1. Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041 China;2. Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433 China
Shanghai Engineering Center of Industrial Asymmetric Catalysis, for Chiral Drugs, Shanghai, 200433 China;3. Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai, 200433 China |
| Abstract: | The Eburnamine-Vincamine alkaloids have been studied intensively over the past six decades for their outstandingly potent vasorelaxation activity. Stereocontrolled assembly of the C20/C21 adjacent chiral centers has been a formidable challenge in the synthesis of this family. Herein, we report a concise stereoselective total synthesis of two trans-ring-fused non-natural analogues, (−)-20-epi-Vincamine and (−)-20-epi-Eburnamonine, that features the following key steps: a) a continuous-flow oxidation/lactam alcoholysis cascade producing the symmetrical dihydro-β-carboline diester precursors, and b) a highly stereoselective Ir/f-Binaphane-catalyzed hydrogenation/lactamization cascade leading to the privileged trans-(20R, 21S) lactam ester scaffold with high-level enantio- and diastereocontrol. |
