TY - JOUR
T1 - Enantioselective total synthesis of (-)-strychnine
T2 - Development of a highly practical catalytic asymmetric carbon-carbon bond formation and domino cyclization
AU - Ohshima, Takashi
AU - Xu, Youjun
AU - Takita, Ryo
AU - Shibasaki, Masakatsu
N1 - Funding Information:
This work was supported by the RFTF and Encouragement of Young Scientists (A) of Japan Society for the Promotion of Science, a Grant-in-Aid for Scientific Research on Priority Areas (A) ‘Exploitation of Multi-Element Cyclic Molecules’ from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, Grant-in-Aid from the Tokyo Biochemical Research Foundation, and fellowship from Heiwa Nakajima Foundation (to Y.X.). We thank Dr. S. Shimizu for his contribution in our initial investigation and Dr. D. Zhong (Syehyang Pharmaceutical University) for help with structural determination using ESI (MS–MS) and TOF mass analyses.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2004/10/18
Y1 - 2004/10/18
N2 - An enantioselective total synthesis of (-)-strychnine was accomplished through the use of the highly practical catalytic asymmetric Michael reaction (0.1 mol% of (R)-ALB, greater than kilogram scale, without chromatography, 91% yield and >99% ee), and a domino cyclization that simultaneously constructed the B- and D- rings of strychnine (>77% yield). Newly-developed reaction conditions for thionium ion cyclization, NaBH3CN reduction of the imine moiety in the presence of a Lewis acid to prevent the ring-opening reaction, and chemoselective reduction of the thioether (desulfurization) in the presence of exocyclic olefin were pivotal to complete the synthesis. The described chemistry paves the way for the synthesis of more advanced Strychnos alkaloids. Graphical Abstract.
AB - An enantioselective total synthesis of (-)-strychnine was accomplished through the use of the highly practical catalytic asymmetric Michael reaction (0.1 mol% of (R)-ALB, greater than kilogram scale, without chromatography, 91% yield and >99% ee), and a domino cyclization that simultaneously constructed the B- and D- rings of strychnine (>77% yield). Newly-developed reaction conditions for thionium ion cyclization, NaBH3CN reduction of the imine moiety in the presence of a Lewis acid to prevent the ring-opening reaction, and chemoselective reduction of the thioether (desulfurization) in the presence of exocyclic olefin were pivotal to complete the synthesis. The described chemistry paves the way for the synthesis of more advanced Strychnos alkaloids. Graphical Abstract.
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U2 - 10.1016/j.tet.2004.06.141
DO - 10.1016/j.tet.2004.06.141
M3 - Article
AN - SCOPUS:4544269722
VL - 60
SP - 9569
EP - 9588
JO - Tetrahedron
JF - Tetrahedron
SN - 0040-4020
IS - 43 SPEC. ISS.
ER -