Stereoselective synthesis of quaternary, α-vinyl amino acids and their α-(2'Z-fluoro)vinyl congeners

Promising candidates for PLP enzyme inactivation

David B Berkowitz, Kannan R. Karukurichi, Roberto De La Salud-Bea, Gourhari Maiti, Jill M. McFadden, Michelle L. Morris

Research output: Chapter in Book/Report/Conference proceedingConference contribution

5 Citations (Scopus)

Abstract

This chapter provides an overview of a program directed at the synthesis of amino acids (AA's) bearing a vinyl substituent in place of the usual α-proton. These quaternary amino acids are of interest, in and of themselves, as mechanism-based inhibitors of pyridoxal phosphate dependent enzymes, and also as building blocks for natural product or peptide synthesis. Importantly, these unnatural amino acids also serve as synthetic precursors for α-halovinyl AA's and α-oxiranyl AA's. Stereoselective synthetic methodology development in this area is highlighted and the initial performance of the α- (2'Z-fluoro)vinyl trigger in an amino acid decarboxylase (AADC) active site is described. Interestingly, at least for H. alvei lysine decarboxylase (LDC), inactivation with this trigger, along the α-branch, displays a marked enantio- dependence, with the L-antipode giving efficient inactivation, and its mirror image behaving as a simple substrate.

Original languageEnglish (US)
Title of host publicationAsymmetric Synthesis and Application of a-Amino Acids
PublisherAmerican Chemical Society
Pages288-303
Number of pages16
ISBN (Print)9780841269743
DOIs
StatePublished - Jun 14 2009

Publication series

NameACS Symposium Series
Volume1009
ISSN (Print)0097-6156
ISSN (Electronic)1947-5918

Fingerprint

Amino acids
Enzymes
Amino Acids
lysine decarboxylase
Bearings (structural)
Pyridoxal Phosphate
Carboxy-Lyases
Biological Products
Peptides
Protons
Mirrors
Phosphates
Substrates

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Berkowitz, D. B., Karukurichi, K. R., De La Salud-Bea, R., Maiti, G., McFadden, J. M., & Morris, M. L. (2009). Stereoselective synthesis of quaternary, α-vinyl amino acids and their α-(2'Z-fluoro)vinyl congeners: Promising candidates for PLP enzyme inactivation. In Asymmetric Synthesis and Application of a-Amino Acids (pp. 288-303). (ACS Symposium Series; Vol. 1009). American Chemical Society. https://doi.org/10.1021/bk-2009-1009.ch018

Stereoselective synthesis of quaternary, α-vinyl amino acids and their α-(2'Z-fluoro)vinyl congeners : Promising candidates for PLP enzyme inactivation. / Berkowitz, David B; Karukurichi, Kannan R.; De La Salud-Bea, Roberto; Maiti, Gourhari; McFadden, Jill M.; Morris, Michelle L.

Asymmetric Synthesis and Application of a-Amino Acids. American Chemical Society, 2009. p. 288-303 (ACS Symposium Series; Vol. 1009).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Berkowitz, DB, Karukurichi, KR, De La Salud-Bea, R, Maiti, G, McFadden, JM & Morris, ML 2009, Stereoselective synthesis of quaternary, α-vinyl amino acids and their α-(2'Z-fluoro)vinyl congeners: Promising candidates for PLP enzyme inactivation. in Asymmetric Synthesis and Application of a-Amino Acids. ACS Symposium Series, vol. 1009, American Chemical Society, pp. 288-303. https://doi.org/10.1021/bk-2009-1009.ch018
Berkowitz DB, Karukurichi KR, De La Salud-Bea R, Maiti G, McFadden JM, Morris ML. Stereoselective synthesis of quaternary, α-vinyl amino acids and their α-(2'Z-fluoro)vinyl congeners: Promising candidates for PLP enzyme inactivation. In Asymmetric Synthesis and Application of a-Amino Acids. American Chemical Society. 2009. p. 288-303. (ACS Symposium Series). https://doi.org/10.1021/bk-2009-1009.ch018
Berkowitz, David B ; Karukurichi, Kannan R. ; De La Salud-Bea, Roberto ; Maiti, Gourhari ; McFadden, Jill M. ; Morris, Michelle L. / Stereoselective synthesis of quaternary, α-vinyl amino acids and their α-(2'Z-fluoro)vinyl congeners : Promising candidates for PLP enzyme inactivation. Asymmetric Synthesis and Application of a-Amino Acids. American Chemical Society, 2009. pp. 288-303 (ACS Symposium Series).
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