The synthesis of (2S)-4,4-difluoroglutamyl γ-peptides based on Garner's aldehyde and fluoro-reformatsky chemistry

David Konas, Jessica J. Pankuch, James K. Coward

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The development of optically active fluorinated synthetic building blocks of general utility is a current goal of organo-fluorine chemists. The serine-derived Garner aldehyde was converted to a general 4,4-difluoroamino acid building block via fluoro-Reformatsky reaction with ethyl bromodifluoroacetate. The utility of this building block was demonstrated by the synthesis of derivatives of (2S)-4,4-difluoroglutamine, (2S)-4,4-difluoroglutamic acid, and its incorporation into a fluorophore-containing isopeptide 2 designed as a mechanistic probe of γ-glutamyl hydrolase. Compound 2 proved to be a substrate for γ-glutamyl hydrolase and was hydrolyzed at a rate significantly slower than the corresponding non-fluorinated analog.

Original languageEnglish
Pages (from-to)2616-2626
Number of pages11
JournalSynthesis
Issue number17
DOIs
StatePublished - 1 Jan 2002

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Hydrolases
Aldehydes
Peptides
Acids
Fluorine
Fluorophores
Serine
Derivatives
Substrates
4,4-difluoroglutamic acid

Keywords

  • Fluorescence enzyme assay
  • Fluoroamino acids
  • Fluoropeptides
  • Stereoselective synthesis
  • γ-glutamyl hydrolase

Cite this

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abstract = "The development of optically active fluorinated synthetic building blocks of general utility is a current goal of organo-fluorine chemists. The serine-derived Garner aldehyde was converted to a general 4,4-difluoroamino acid building block via fluoro-Reformatsky reaction with ethyl bromodifluoroacetate. The utility of this building block was demonstrated by the synthesis of derivatives of (2S)-4,4-difluoroglutamine, (2S)-4,4-difluoroglutamic acid, and its incorporation into a fluorophore-containing isopeptide 2 designed as a mechanistic probe of γ-glutamyl hydrolase. Compound 2 proved to be a substrate for γ-glutamyl hydrolase and was hydrolyzed at a rate significantly slower than the corresponding non-fluorinated analog.",
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The synthesis of (2S)-4,4-difluoroglutamyl γ-peptides based on Garner's aldehyde and fluoro-reformatsky chemistry. / Konas, David; Pankuch, Jessica J.; Coward, James K.

In: Synthesis, No. 17, 01.01.2002, p. 2616-2626.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The synthesis of (2S)-4,4-difluoroglutamyl γ-peptides based on Garner's aldehyde and fluoro-reformatsky chemistry

AU - Konas, David

AU - Pankuch, Jessica J.

AU - Coward, James K.

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AB - The development of optically active fluorinated synthetic building blocks of general utility is a current goal of organo-fluorine chemists. The serine-derived Garner aldehyde was converted to a general 4,4-difluoroamino acid building block via fluoro-Reformatsky reaction with ethyl bromodifluoroacetate. The utility of this building block was demonstrated by the synthesis of derivatives of (2S)-4,4-difluoroglutamine, (2S)-4,4-difluoroglutamic acid, and its incorporation into a fluorophore-containing isopeptide 2 designed as a mechanistic probe of γ-glutamyl hydrolase. Compound 2 proved to be a substrate for γ-glutamyl hydrolase and was hydrolyzed at a rate significantly slower than the corresponding non-fluorinated analog.

KW - Fluorescence enzyme assay

KW - Fluoroamino acids

KW - Fluoropeptides

KW - Stereoselective synthesis

KW - γ-glutamyl hydrolase

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