Enantioselective total synthesis of (-)-strychnine using the catalytic asymmetric Michael reaction and tandem cyclization

Takashi Ohshima, Youjun Xu, Ryo Takita, Satoshi Shimizu, Dafang Zhong, Masakatsu Shibasaki

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

The enantioselective total synthesis of (-)-strychnine was accomplished through the use of the highly practical catalytic asymmetric Michael reaction (0.1 mol % of (R)-ALB, more than kilogram scale, without chromatography, 91% yield and >99% ee) as well as a tandem cyclization that simultaneously constructed B- and D-rings (>77% yield). Moreover, newly developed reaction conditions for thionium ion cyclization, NaBH3CN reduction of the imine moiety in the presence of Lewis acid to prevent 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.

Original languageEnglish
Pages (from-to)14546-14547
Number of pages2
JournalJournal of the American Chemical Society
Volume124
Issue number49
DOIs
Publication statusPublished - Dec 11 2002
Externally publishedYes

Fingerprint

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

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Enantioselective total synthesis of (-)-strychnine using the catalytic asymmetric Michael reaction and tandem cyclization. / Ohshima, Takashi; Xu, Youjun; Takita, Ryo; Shimizu, Satoshi; Zhong, Dafang; Shibasaki, Masakatsu.

In: Journal of the American Chemical Society, Vol. 124, No. 49, 11.12.2002, p. 14546-14547.

Research output: Contribution to journalArticle

Ohshima, Takashi ; Xu, Youjun ; Takita, Ryo ; Shimizu, Satoshi ; Zhong, Dafang ; Shibasaki, Masakatsu. / Enantioselective total synthesis of (-)-strychnine using the catalytic asymmetric Michael reaction and tandem cyclization. In: Journal of the American Chemical Society. 2002 ; Vol. 124, No. 49. pp. 14546-14547.
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