Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 9569-9588 |
| Number of pages | 20 |
| Journal | Tetrahedron |
| Volume | 60 |
| Issue number | 43 SPEC. ISS. |
| DOIs | |
| Publication status | Published - Oct 18 2004 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Drug Discovery
- Organic Chemistry
Cite this
Enantioselective total synthesis of (-)-strychnine : Development of a highly practical catalytic asymmetric carbon-carbon bond formation and domino cyclization. / Ohshima, Takashi; Xu, Youjun; Takita, Ryo; Shibasaki, Masakatsu.
In: Tetrahedron, Vol. 60, No. 43 SPEC. ISS., 18.10.2004, p. 9569-9588.Research output: Contribution to journal › Article
}
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
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.
UR - http://www.scopus.com/inward/record.url?scp=4544269722&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4544269722&partnerID=8YFLogxK
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 -