New fluorinated peptidomimetics through tandem aza-michael addition to α-trifluoromethyl acrylamide acceptors

synthesis and conformational study in solid state and solution

Santos Fustero, Gema Chiva, Julio Piera, Juan F Sanz-Cervera, Alessandro Volonterio, Matteo Zanda, Carmen Ramirez de Arellano

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

A range of partially modified retro (PMR) psi[NHCH(2)] peptide mimetics containing a hydrolytically stable CH(2)CH(CF(3))CO unit have been synthesized. The first kind of peptidomimetics is obtained from the highly efficient aza-Michael addition of different amines to alpha-trifluoromethyl acrylamide acceptors. Subsequent deprotection of the amino group furnishes the key common intermediate for the synthesis of other families of peptidomimetics: dipeptides, tripeptides, peptidomimetics containing a urea moiety, and structures containing two units of alpha-trifluoromethyl-beta(2)-alanine. Finally, a conformational study of several of the newly synthesized peptidomimetics, performed with the aid of X-ray analysis and NMR techniques, shows a beta-turn-like conformation for the structures both in the solid state and in solution.
Original languageEnglish
Pages (from-to)3122-3132
Number of pages11
JournalJournal of Organic Chemistry
Volume74
Issue number8
Early online date23 Mar 2009
DOIs
Publication statusPublished - 17 Apr 2009

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Peptidomimetics
Acrylamide
Dipeptides
X ray analysis
Carbon Monoxide
Amines
Conformations
Urea
Nuclear magnetic resonance
Peptides

Keywords

  • acrylamides
  • alanine
  • aza compounds
  • crystallography, x-ray
  • fluorine compounds
  • magnetic resonance spectroscopy
  • molecular conformation
  • peptides
  • solutions

Cite this

New fluorinated peptidomimetics through tandem aza-michael addition to α-trifluoromethyl acrylamide acceptors : synthesis and conformational study in solid state and solution. / Fustero, Santos; Chiva, Gema; Piera, Julio; Sanz-Cervera, Juan F; Volonterio, Alessandro; Zanda, Matteo; Ramirez de Arellano, Carmen.

In: Journal of Organic Chemistry, Vol. 74, No. 8, 17.04.2009, p. 3122-3132.

Research output: Contribution to journalArticle

Fustero, Santos ; Chiva, Gema ; Piera, Julio ; Sanz-Cervera, Juan F ; Volonterio, Alessandro ; Zanda, Matteo ; Ramirez de Arellano, Carmen. / New fluorinated peptidomimetics through tandem aza-michael addition to α-trifluoromethyl acrylamide acceptors : synthesis and conformational study in solid state and solution. In: Journal of Organic Chemistry. 2009 ; Vol. 74, No. 8. pp. 3122-3132.
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abstract = "A range of partially modified retro (PMR) psi[NHCH(2)] peptide mimetics containing a hydrolytically stable CH(2)CH(CF(3))CO unit have been synthesized. The first kind of peptidomimetics is obtained from the highly efficient aza-Michael addition of different amines to alpha-trifluoromethyl acrylamide acceptors. Subsequent deprotection of the amino group furnishes the key common intermediate for the synthesis of other families of peptidomimetics: dipeptides, tripeptides, peptidomimetics containing a urea moiety, and structures containing two units of alpha-trifluoromethyl-beta(2)-alanine. Finally, a conformational study of several of the newly synthesized peptidomimetics, performed with the aid of X-ray analysis and NMR techniques, shows a beta-turn-like conformation for the structures both in the solid state and in solution.",
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KW - acrylamides

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KW - aza compounds

KW - crystallography, x-ray

KW - fluorine compounds

KW - magnetic resonance spectroscopy

KW - molecular conformation

KW - peptides

KW - solutions

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