(2R,3S)-3,4,4,4-Tetrafluorovaline: A Fluorinated Bioisostere of Isoleucine

Lennart Brewitz, Hidetoshi Noda, Naoya Kumagai, Masakatsu Shibasaki

Research output: Contribution to journalArticlepeer-review

Abstract

The synthesis of (2R,3S)-3,4,4,4-tetrafluorovaline, a fluorinated derivative of the canonical α-amino acid l-valine, is reported for the first time. A highly enantio- and diastereoselective direct catalytic asymmetric Mannich-type reaction was applied as the key C–C bond-forming step to afford gram quantities of a central synthetic intermediate. The conformation of the novel fluorinated α-amino acid was analyzed by X-ray crystallography, NMR spectroscopy, and computational methods, which, together with its calculated and experimental physicochemical properties, indicated that the fluorinated valine is a bioisostere of l-isoleucine.

Original languageEnglish
Pages (from-to)1745-1752
Number of pages8
JournalEuropean Journal of Organic Chemistry
Volume2020
Issue number11
DOIs
Publication statusPublished - 2020 Mar 22
Externally publishedYes

Keywords

  • Bioisosterism
  • Conformational analysis
  • Cooperative catalysis
  • Fluorinated amino acid
  • Physicochemical properties

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

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