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Total Synthesis of (±)‐Corymine
Author(s) -
Zhang Benxiang,
Wang Xiaoqing,
Cheng Chao,
Sun Deqian,
Li Chaozhong
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201704086
Subject(s) - chemistry , total synthesis , tryptamine , oxindole , intramolecular force , stereochemistry , ketone , claisen rearrangement , stereocenter , stereoselectivity , aldol reaction , indole test , medicinal chemistry , enantioselective synthesis , organic chemistry , biochemistry , catalysis
The first total synthesis of the hexacyclic indole alkaloid (±)‐corymine is described. Starting from the readily available N‐protected tryptamine, the title compound was achieved in 21 steps in 3.4 % overall yield. Key steps of the synthesis include: a) the addition of a malonate to a 3‐bromooxindole to afford 3,3‐disubstituted oxindole, b) the formation of a 12‐membered cyclic enol ether by intramolecular O‐propargylation, immediately followed by propargyl Claisen rearrangement to provide the α‐allenyl ketone stereospecifically, c) DMDO oxidation to install a hydroxy group in a highly stereoselective manner, and d) the SmI 2 ‐mediated reductive C−O bond cleavage to remove the α‐keto carboxyl group.