Efficient Peptide Coupling Involving Sterically Hindered Amino Acids

Hindered amino acids have been introduced into peptide chains by coupling N-(Cbz- and Fmoc-α-aminoacyl)benzotriazoles with amino acids, wherein at least one of the components was sterically hindered,
to provide compounds 3a−e, (3c +3 c‘), 5a−d, (5a + 5a‘), 6a−c, (6b + 6b‘), 8a−c, 9a−e, 10a−d, and
(10a + 10a‘) in isolated yields of 41−95% with complete retention of chirality as evidenced by NMR
and HPLC analysis. The benzotriazole activation methodology is a new route for the synthesis of sterically
hindered peptides. (Note:  compound numbers written within brackets represent diastereomeric mixtures
or racemates; compound numbers without brackets represent enantiomers.)