A convenient synthesis of amino acid p-nitroanilides: Synthons in the synthesis of protease substrates

Dirk R.S. Rijkers, Hans P.H.M. Adams, H. Coenraad Hemker, Godefridus I. Tesser

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    A method is described for the synthesis of N-alpha-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(a)lpha-protective functions or allyl-derived protections, but also with N-alpha-trityl 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 languageEnglish
    Pages (from-to)11235-11250
    Number of pages16
    Issue number41
    Publication statusPublished - 9 Oct 1995

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