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Asymmetric Total Synthesis of Norzoanthamine
Author(s) -
Xin Zhengyuan,
Wang Hui,
He Haibing,
Zhao Xiaoli,
Gao Shuanhu
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202102643
Subject(s) - stereocenter , radical cyclization , total synthesis , chemistry , vicinal , stereochemistry , olefin fiber , acetal , catalysis , combinatorial chemistry , enantioselective synthesis , organic chemistry
We report herein the asymmetric total synthesis of norzoanthamine using radical reactions as key steps for rapid access to the congested carbocyclic core, which is the major synthetic challenge for most zoanthamine alkaloids. (1) The Ueno–Stork radical cyclization was applied to construct the adjacent quaternary centers at the C‐9 and C‐22 positions; (2) a Co‐catalyzed HAT radical reaction was successfully applied to construct the quaternary center at C‐12 via Csp 3 ‐Csp 2 bond formation; (3) a Mn‐catalyzed HAT radical reaction was used to stereospecifically reduce the tetra‐substituted olefin (C13=C18) and install the contiguous stereocenters in proximity to the quaternary center. A one‐pot bio‐inspired cyclization step was finally applied to forge the unstable bis‐amino acetal skeleton. Our approach can precisely control the stereochemistry of seven vicinal stereocenters and effectively construct the highly congested heptacyclic skeleton.