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Enantioselective Synthesis and Racemization of (−)‐Sinoracutine
Author(s) -
Volpin Giulio,
Vepřek Nynke A.,
Bellan Andreas B.,
Trauner Dirk
Publication year - 2017
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.201608206
Subject(s) - racemization , stereocenter , enantioselective synthesis , cyclopentenone , chemistry , stereochemistry , enantiomer , absolute configuration , stereoisomerism , ring (chemistry) , molecule , organic chemistry , catalysis
Sinoracutine is a recently isolated alkaloid with unusual stereochemical and biological properties. It features an unprecedented tetracyclic 6/6/5/5 skeleton that bears an N ‐methylpyrrolidine ring fused to a cyclopentenone. Interestingly, both enantiomers of sinoracutine have been independently isolated from the same plant, yet the molecule does not appear to occur as a racemate. Here, we present a short synthesis of (−)‐sinoracutine that relies on a highly diastereoselective Pauson–Khand reaction and a Mandai–Claisen reaction to install the quaternary stereocenter. Our work establishes the absolute configuration of the levorotatory isomer and suggests that the optical purity of sinoracutine varies in nature due to its gradual racemization. Experimental evidence supports this proposal, and a plausible mechanism for the racemization is provided.