Synthesis of chaetomellic anhydride A, A potent inhibitor of ras protein farnesyltransferase

Takehiko Yoshimitsu, Yoshimasa Arano, Tomohiro Kaji, Tatsunori Ino, Hiroto Nagaoka, Tetsuaki Tanaka

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Chaetomellic anhydride A, a potent inhibitor of Ras protein farnesyltransferase, was synthesized in 61% yield over four steps from methyl propionate. The synthesis features palladium-catalyzed carboxylation reaction under Cacchi conditions, efficiently incorporating carbon monoxide generated in situ from acetic formic anhydride into β-carbomethoxyalkenyl inflate, and giving rise to the maleic anhydride motif of chaetomellic anhydride A. Noteworthy is the remarkable reactivity of the carboxylation reaction that takes place at room temperature despite the fact that common palladium-catalyzed carboxylations generally require rather harsh conditions. The scope of the method is also presented.

Original languageEnglish
Pages (from-to)179-186
Number of pages8
JournalHeterocycles
Volume77
Issue number1
DOIs
Publication statusPublished - Jan 1 2009
Externally publishedYes

Fingerprint

Carboxylation
ras Proteins
Anhydrides
Palladium
Maleic Anhydrides
Propionates
Carbon Monoxide
Acetic Acid
Temperature
p21(ras) farnesyl-protein transferase
acetic anhydride

Keywords

  • Anticancer
  • Carbonylation
  • Maleic Anhydride
  • Palladium-Catalyzed
  • Total Synthesis

ASJC Scopus subject areas

  • Analytical Chemistry
  • Organic Chemistry
  • Pharmacology

Cite this

Synthesis of chaetomellic anhydride A, A potent inhibitor of ras protein farnesyltransferase. / Yoshimitsu, Takehiko; Arano, Yoshimasa; Kaji, Tomohiro; Ino, Tatsunori; Nagaoka, Hiroto; Tanaka, Tetsuaki.

In: Heterocycles, Vol. 77, No. 1, 01.01.2009, p. 179-186.

Research output: Contribution to journalArticle

Yoshimitsu, Takehiko ; Arano, Yoshimasa ; Kaji, Tomohiro ; Ino, Tatsunori ; Nagaoka, Hiroto ; Tanaka, Tetsuaki. / Synthesis of chaetomellic anhydride A, A potent inhibitor of ras protein farnesyltransferase. In: Heterocycles. 2009 ; Vol. 77, No. 1. pp. 179-186.
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