Efficient synthesis of peptides by extension at the N- and C-terminii of arginine

L-N(omega)-nitroarginine and L-arginine were coupled with N-(Cbz-alpha-aminoacyl)benzotriazoles and N-Cbz-dipeptidoylbenzotriazoles to provide arginine LL-dipeptides 9a-e, 11a-d; LLL-tripeptides 18a-c, 20; and diastereomeric mixtures (9b+9b'), (9c+9c'), (11b+11b') and (18c+18c') [compound numbers written within parentheses represent a diastereomeric mixture or racemate; compound numbers without parentheses represent an achiral compound or a single enantiomer] by extension at the N-terminus of arginine, in isolated yields of 66-95% with complete retention of chirality as evidenced by NMR and HPLC analysis. Arginine LL-dipeptides 15a-d were synthesized by extension at the C-terminus of arginine in isolated yield of 66-80%, using benzotriazole activated arginine L-(omega)NO2-Arg-Bt, 13. Our methodology has also been used to synthesize the protected RGD peptide (Cbz(alpha)-L-(omega)NO2-Arg-Gly-L-Asp-(OH)2) 21.