A novel high-yield synthesis of aminoacyl p-nitroanilines and aminoacyl 7-amino-4-methylcoumarins

Important synthons for the synthesis of chromogenic/fluorogenic protease substrates

Xinghua Wu, Yu Chen, Herve Aloysius, Longqin Hu

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Aminoacyl p-nitroaniline (aminoacyl-pNA) and aminoacyl 7-amino-4- methylcoumarin (aminoacyl-AMC) are important synthons for the synthesis of chromogenic/fluorogenic protease substrates. A new efficient method was developed to synthesize aminoacylpNA and aminoacyl-AMC derivatives in excellent yields starting from either amino acids or their corresponding commercially available N-hydroxysuccinimide esters. The method involved the in situ formation of selenocarboxylate intermediate of protected amino acids and the subsequent non-nucleophilic amidation with an azide. Common protecting groups used in amino acid/peptide chemistry were all well-tolerated. The method was also successfully applied to the synthesis of a dipeptide conjugate, indicating that the methodology is applicable to the synthesis of chromogenic substrates containing short peptides. The method has general applicability to the synthesis of chromogenic and fluorogenic peptide substrates and represents a convenient and high-yield synthesis of Nα-protected-aminoacyl-pNAs/AMCs, providing easy access to these important synthons for the construction of chromogenic/ fluorogenic protease substrates through fragment condensation or stepwise elongation.

Original languageEnglish (US)
Article number117
Pages (from-to)1030-1035
Number of pages6
JournalBeilstein Journal of Organic Chemistry
Volume7
DOIs
StatePublished - Jul 27 2011

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Chromogenics
Peptide Hydrolases
Substrates
Amino Acids
Peptides
Chromogenic Compounds
Azides
Dipeptides
Elongation
Condensation
Esters
7-amino-4-methylcoumarin
4-nitroaniline
Derivatives

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Keywords

  • 7-amino-4-methylcoumarin
  • P-nitroaniline
  • Proteolytic substrate
  • Selenocarboxylate/azide amidation
  • Synthon

Cite this

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title = "A novel high-yield synthesis of aminoacyl p-nitroanilines and aminoacyl 7-amino-4-methylcoumarins: Important synthons for the synthesis of chromogenic/fluorogenic protease substrates",
abstract = "Aminoacyl p-nitroaniline (aminoacyl-pNA) and aminoacyl 7-amino-4- methylcoumarin (aminoacyl-AMC) are important synthons for the synthesis of chromogenic/fluorogenic protease substrates. A new efficient method was developed to synthesize aminoacylpNA and aminoacyl-AMC derivatives in excellent yields starting from either amino acids or their corresponding commercially available N-hydroxysuccinimide esters. The method involved the in situ formation of selenocarboxylate intermediate of protected amino acids and the subsequent non-nucleophilic amidation with an azide. Common protecting groups used in amino acid/peptide chemistry were all well-tolerated. The method was also successfully applied to the synthesis of a dipeptide conjugate, indicating that the methodology is applicable to the synthesis of chromogenic substrates containing short peptides. The method has general applicability to the synthesis of chromogenic and fluorogenic peptide substrates and represents a convenient and high-yield synthesis of Nα-protected-aminoacyl-pNAs/AMCs, providing easy access to these important synthons for the construction of chromogenic/ fluorogenic protease substrates through fragment condensation or stepwise elongation.",
keywords = "7-amino-4-methylcoumarin, P-nitroaniline, Proteolytic substrate, Selenocarboxylate/azide amidation, Synthon",
author = "Xinghua Wu and Yu Chen and Herve Aloysius and Longqin Hu",
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T1 - A novel high-yield synthesis of aminoacyl p-nitroanilines and aminoacyl 7-amino-4-methylcoumarins

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AU - Wu, Xinghua

AU - Chen, Yu

AU - Aloysius, Herve

AU - Hu, Longqin

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KW - Selenocarboxylate/azide amidation

KW - Synthon

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