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

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

Research output: Contribution to journalArticle

79 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 - Jan 7 2014
Externally publishedYes

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Amides
Aldehydes
Esters
Allylation
Redox reactions
Functional groups
gephyrotoxin

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Catalysis

Cite this

Total synthesis of (±)-gephyrotoxin by amide-selective reductive nucleophilic addition. / Shirokane, Kenji; Wada, Takamasa; Yoritate, Amakoto; Minamikawa, Ryo; Takayama, Nobuaki; Sato, Takaaki; Chida, Noritaka.

In: Angewandte Chemie - International Edition, Vol. 53, No. 2, 07.01.2014, p. 512-516.

Research output: Contribution to journalArticle

Shirokane, Kenji ; Wada, Takamasa ; Yoritate, Amakoto ; Minamikawa, Ryo ; Takayama, Nobuaki ; Sato, Takaaki ; Chida, Noritaka. / Total synthesis of (±)-gephyrotoxin by amide-selective reductive nucleophilic addition. In: Angewandte Chemie - International Edition. 2014 ; Vol. 53, No. 2. pp. 512-516.
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