Urethane-protected α-amino acid N-carboxyanhydrides and peptide synthesis

Abstract

The preparation, physical properties and analytical data are reported for seventy urethane-protected (Boc, Cbz, FMOC) amino acid N-carboxyanhydrides (UNCAs). Most of the UNCAs are crystalline and the X-ray diffraction patterns for several of these are described. UNCAs are stable to routine laboratory manipulations and can be stored for extended periods of time (1-2 years at below 0°C). Most are completely stable to the conditions commonly employed for peptide synthesis. The correct choice of base is key for the successful introduction of urethane protecting groups into NCAs. N-Methylmorpholine is used for the introduction of FMOC, Cbz or Boc from the chloroformates, and pyridine is used for the introduction of the Boc group from Boc anhydride. UNCAs represent a unique class of preactivated, isolable and stable amino acid derivatives that generate no side products or co-products, other than CO2, during condensation reactions. The application of UNCAs in peptide synthesis in both solid phase and in solution is reviewed in detail. © 1996 John Wiley & Sons, Inc.