N-(Cbz- and Fmoc-α-aminoacyl)benzotriazoles: Stable Derivatives Enabling Peptide Coupling of Tyr, Trp, Cys, Met, and Gln with Free Amino Acids in Aqueous Media with Complete Retention of Chirality

Abstract

Crystalline, chirally stable N-(Cbz- and Fmoc-α-aminoacyl)benzotriazoles 2a-f, activated derivatives of Tyr, Trp, Cys, Met and Gln undergo peptide coupling in aqueous media with unprotected L-Ala-OH and L-Phe-OH to give the chiral dipeptides in 70-98% yield. A convenient and efficient procedure under mild reaction conditions for the preparation of 2a-f in 72-95% yield utilizes N-Cbz- or N-Fmoc-protected α-amino acids 1a-f.