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Enantioselective Total Syntheses of (−)‐20‐ epi ‐Vincamine and (−)‐20‐ epi ‐Eburnamonine by Ir‐Catalyzed Asymmetric Imine Hydrogenation/Lactamization Cascade
Author(s) -
Zhang Wen,
Chen Xiangtao,
An Yi,
Wang Jiaqi,
Zhuang Chunlin,
Tang Pei,
Chen Fener
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202002404
Subject(s) - stereoselectivity , chemistry , imine , enantioselective synthesis , cascade , stereochemistry , catalysis , combinatorial chemistry , cascade reaction , lactam , ring (chemistry) , organic chemistry , chromatography
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 ‐(20 R , 21 S ) lactam ester scaffold with high‐level enantio‐ and diastereocontrol.