Large-scale asymmetric synthesis of novel sterically constrained 2 ',6 '-dimethyl- and alpha,2 ',6 '-trimethyltyrosine and -phenylalanine derivativesvia alkylation of chiral equivalents of nucleophilic glycine and alanine

Asymmetric synthesis of (S)-2 ' ,6 ' -dimethyltyrosine (DMT), (S)-2 ' ,6 ' -dimethylphenylalanine (DMP), (S)-alpha ,2 ' ,6 ' -trimethyltyrosine (alpha -TMT) and (S)-alpha ,2 ' ,6 ' -trimethylphenylalanine (alpha -TMP) via rea ctions of 4 ' -benzyloxy-2 ' ,6 ' -dimethylbenzyl bromide or 2 ' ,6 ' -dime thylbenzylbromide with Ni(II)-complexes of the chiral Schiff base of glycin e or alanine with (S)-o-[N-(N-benzylprolyl)amino] benzophenone were develop ed. Inexpensive and readily available reagents and solvents, a recyclable c hiral auxiliary, simplicity of the experimental procedures and high chemica l yields make this method synthetically attractive for preparing the target amino acids on a multi-gram scale. (C) 2001 Elsevier Science Ltd. All righ ts reserved.