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Collective Asymmetric Total Synthesis of C‐11 Oxygenated Cephalotaxus Alkaloids
Author(s) -
Kim Jae Hyun,
Jeon Hongjun,
Park Choyi,
Park Soojun,
Kim Sanghee
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202101766
Subject(s) - stereocenter , stereospecificity , total synthesis , chemistry , chirality (physics) , stereochemistry , alkylation , intramolecular force , stereoselectivity , axial chirality , enantioselective synthesis , organic chemistry , catalysis , chiral symmetry , nambu–jona lasinio model , physics , quantum mechanics , quark
While numerous studies pertaining to the total synthesis of Cephalotaxus alkaloids have been reported, only two strategies have been reported to date for the successful synthesis of the C‐11 oxygenated subset, due to the additional synthetic challenge posed by the remote C‐11 stereocenter. Herein, we report the collective asymmetric total synthesis of C‐11 oxygenated Cephalotaxus alkaloids using a chiral proline both as a starting material and as the only chirality source. A tetracyclic advanced intermediate was synthesized in a highly stereoselective manner from l ‐proline in 8 steps involving sequential chirality transfer steps such as a diastereoselective N ‐alkylation, stereospecific Stevens rearrangement and intramolecular Friedel–Crafts reaction via an unusual O ‐acyloxocarbenium intermediate. From a common intermediate, the asymmetric total synthesis of six C‐11 oxygenated Cephalotaxus alkaloids was completed by a series of oxidation state adjustments.