Formal total synthesis of (+)-wortmannin using catalytic asymmetric intramolecular aldol condensation reaction

Hiroki Shigehisa, Takashi Mizutani, Shin Ya Tosaki, Takashi Ohshima, Masakatsu Shibasaki

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

A catalytic process for the synthesis of optically active C4-substituted tetrahydroindandiones using an asymmetric intramolecular aldol condensation reaction was developed. When 30 mol% of phenylalanine and 50 mol% of pyridinium p-toluenesulfonate were used under highly concentrated conditions, a variety of C4-substituted tetrahydroindandiones and octahydronaphthalenediones were obtained in high yield (up to 89% yield) and high enantiomeric excess (up to 94% ee). One of the products was successfully transformed into the key intermediate for the synthesis of the phosphatidylinositol 3-kinase inhibitor wortmannin, achieving formal total synthesis of (+)-wortmannin.

Original languageEnglish
Pages (from-to)5057-5065
Number of pages9
JournalTetrahedron
Volume61
Issue number21
DOIs
Publication statusPublished - May 23 2005

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Condensation reactions
Phosphatidylinositol 3-Kinase
Phenylalanine
3-hydroxybutanal
wortmannin
4-toluenesulfonic acid

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Formal total synthesis of (+)-wortmannin using catalytic asymmetric intramolecular aldol condensation reaction. / Shigehisa, Hiroki; Mizutani, Takashi; Tosaki, Shin Ya; Ohshima, Takashi; Shibasaki, Masakatsu.

In: Tetrahedron, Vol. 61, No. 21, 23.05.2005, p. 5057-5065.

Research output: Contribution to journalArticle

Shigehisa, Hiroki ; Mizutani, Takashi ; Tosaki, Shin Ya ; Ohshima, Takashi ; Shibasaki, Masakatsu. / Formal total synthesis of (+)-wortmannin using catalytic asymmetric intramolecular aldol condensation reaction. In: Tetrahedron. 2005 ; Vol. 61, No. 21. pp. 5057-5065.
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