A convenient synthesis of amino acid p-nitroanilides; synthons in the synthesis of protease substrates

Dirk T.S. Rijkers; Hans P.H.M. Adams; H. Coenraad Hemker; Godefridus I. Tesser

doi:10.1016/0040-4020(95)00671-T

A convenient synthesis of amino acid p-nitroanilides; synthons in the synthesis of protease substrates

Dirk T.S. Rijkers^*
, Hans P.H.M. Adams
, H. Coenraad Hemker
, Godefridus I. Tesser

^*Corresponding author for this work

Radboud University Nijmegen
Maastricht University
extern

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

A method is described for the synthesis of N^α-protected bi- and trifunctional amino acid p-nitroanilides. The reaction uses phosphorus oxychloride as the condensing agent. The synthesis is simple, rapid, free of racemization and affords yields between 70-90%. The synthesis can be performed not only with amino acid derivatives of the urethane type including acid-labile (Z. Boc) and base-labile (Fmoc, Msc) N^α-proteclivc functions or allyl-derived protections, but also with N^α-trilyl amino acids, albeit in lower yield. The reaction runs in pyridine and its mechanism implies carboxyl activation by formation of a mixed anhydride with phosphorodichloridic acid (HOPOCl₂).

Original language	English
Pages (from-to)	11235-11250
Number of pages	16
Journal	Tetrahedron
Volume	51
Issue number	41
DOIs	https://doi.org/10.1016/0040-4020(95)00671-T
Publication status	Published - 9 Oct 1995
Externally published	Yes

Funding

AcknnwlrdRemr~rrs: We thank L.H. Koole, A.P. van der Heijden (University of Limburg) and A. Swolfs (Catholic University of Nijmegen) for recording the NMR spectra, H. Amatdjais-Groenen (Catholic University of Nijmegen) for performing the elemental analysis and J. Kamphuis (DSM Research, Geleen) for financial support and the kind gift of D-phenylalanine.

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title = "A convenient synthesis of amino acid p-nitroanilides; synthons in the synthesis of protease substrates",

abstract = "A method is described for the synthesis of Nα-protected bi- and trifunctional amino acid p-nitroanilides. The reaction uses phosphorus oxychloride as the condensing agent. The synthesis is simple, rapid, free of racemization and affords yields between 70-90\%. The synthesis can be performed not only with amino acid derivatives of the urethane type including acid-labile (Z. Boc) and base-labile (Fmoc, Msc) Nα-proteclivc functions or allyl-derived protections, but also with Nα-trilyl amino acids, albeit in lower yield. The reaction runs in pyridine and its mechanism implies carboxyl activation by formation of a mixed anhydride with phosphorodichloridic acid (HOPOCl2).",

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year = "1995",

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doi = "10.1016/0040-4020(95)00671-T",

language = "English",

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T1 - A convenient synthesis of amino acid p-nitroanilides; synthons in the synthesis of protease substrates

AU - Rijkers, Dirk T.S.

AU - Adams, Hans P.H.M.

AU - Hemker, H. Coenraad

AU - Tesser, Godefridus I.

PY - 1995/10/9

Y1 - 1995/10/9

N2 - A method is described for the synthesis of Nα-protected bi- and trifunctional amino acid p-nitroanilides. The reaction uses phosphorus oxychloride as the condensing agent. The synthesis is simple, rapid, free of racemization and affords yields between 70-90%. The synthesis can be performed not only with amino acid derivatives of the urethane type including acid-labile (Z. Boc) and base-labile (Fmoc, Msc) Nα-proteclivc functions or allyl-derived protections, but also with Nα-trilyl amino acids, albeit in lower yield. The reaction runs in pyridine and its mechanism implies carboxyl activation by formation of a mixed anhydride with phosphorodichloridic acid (HOPOCl2).

AB - A method is described for the synthesis of Nα-protected bi- and trifunctional amino acid p-nitroanilides. The reaction uses phosphorus oxychloride as the condensing agent. The synthesis is simple, rapid, free of racemization and affords yields between 70-90%. The synthesis can be performed not only with amino acid derivatives of the urethane type including acid-labile (Z. Boc) and base-labile (Fmoc, Msc) Nα-proteclivc functions or allyl-derived protections, but also with Nα-trilyl amino acids, albeit in lower yield. The reaction runs in pyridine and its mechanism implies carboxyl activation by formation of a mixed anhydride with phosphorodichloridic acid (HOPOCl2).

UR - https://www.scopus.com/pages/publications/0029033269

U2 - 10.1016/0040-4020(95)00671-T

DO - 10.1016/0040-4020(95)00671-T

M3 - Article

AN - SCOPUS:0029033269

SN - 0040-4020

VL - 51

SP - 11235

EP - 11250

JO - Tetrahedron

JF - Tetrahedron

IS - 41

ER -

A convenient synthesis of amino acid p-nitroanilides; synthons in the synthesis of protease substrates

Abstract

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