Total synthesis of (±)-gephyrotoxin by amide-selective reductive nucleophilic addition

Kenji Shirokane, Takamasa Wada, Makoto Yoritate, Ryo Minamikawa, Nobuaki Takayama, Takaaki Sato, Noritaka Chida

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

A chemoselective approach for the total synthesis of (±)- gephyrotoxin has been developed. The key to success was the utilization of N-methoxyamides, which enabled the direct coupling of the amide with an aldehyde and selective reductive nucleophilic addition to the amide in the presence of a variety of sensitive and electrophilic functional groups, such as a methyl ester. This chemoselective approach minimized the use of protecting-group manipulations and redox reactions, which resulted in the most concise and efficient total synthesis of (±)-gephyrotoxin described to date. Aim for selectivity: A chemoselective approach that utilizes N-methoxyamides has been developed for the total synthesis of (±)-gephyrotoxin. The N-methoxy group enabled the direct coupling of the amide with an aldehyde and amide-selective reductive allylation in the presence of a more electrophilic methyl ester, which resulted in the most concise and efficient total synthesis of (±)-gephyrotoxin described to date.

Original languageEnglish
Pages (from-to)512-516
Number of pages5
JournalAngewandte Chemie - International Edition
Volume53
Issue number2
DOIs
Publication statusPublished - 2014 Jan 7

Keywords

  • amides
  • chemoselectivity
  • gephyrotoxin
  • nucleophilic addition
  • total synthesis

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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