Enantioselective total synthesis of (-)-strychnine: Development of a highly practical catalytic asymmetric carbon-carbon bond formation and domino cyclization

Takashi Ohshima, Youjun Xu, Ryo Takita, Masakatsu Shibasaki

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 languageEnglish
Pages (from-to)9569-9588
Number of pages20
JournalTetrahedron
Volume60
Issue number43 SPEC. ISS.
DOIs
Publication statusPublished - Oct 18 2004
Externally publishedYes

Fingerprint

Strychnine
Cyclization
Carbon
Strychnos
Lewis Acids
Imines
Alkenes
Sulfides
Alkaloids
Chromatography
Ions
Desulfurization
thionium

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 journalArticle

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