N-Carbamoyl Derivatives and Their Nitrosation by Gaseous NOx − A New, Promising Tool in Stepwise Peptide Synthesis

Abstract

New uses of the N-carbamoyl group in peptide synthesis − as an Nα-protecting group in classical peptide coupling methods, and as a preactivating group for stepwise coupling by NCA formation − are presented. In the first application, the N-carbamoyldipeptide esters C-Val-Gly-OEt, C-Leu-Gly-OEt, C-Ala-Gly-OEt, and C-Ala-Phe-OEt were obtained in good yields by treatment of the corresponding N-carbamoylamino acids (CAA) with amino acid esters. Quantitative N-deprotection without racemisation was then achieved in the solid through nitrosation by gaseous NOx. The extent of racemisation occurring in the coupling step is discussed. In the second application, an easy route to amino acid N-carboxy anhydrides (NCAs) through nitrosation of CAA under the same conditions as above allowed straightforward “one-pot” peptide stepwise coupling, as demonstrated by the formation of Leu-Gly and Val-Gly in good yields and enantiomeric excess. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)