Total asymmetric synthesis of highly constrained amino acids beta-isopropyl-2',6'-dimethyl-tyrosines

All four stereoisomers of the highly constrained aromatic alpha-amino acid beta-isopropyl-2',6'-dimethyltyrosine have been asymmetrically synthesized on a large scale. A catalytic asymmetric Michael addition of an organocuprate to a chiral alpha,beta-unsaturated acyloxazolidinone and subsequent direct or indirect stereoselective electrophilic azidation of the alpha-position of the resulting product was followed by hydrolysis, hydrogenation and finally deprotection of the phenol group to afford the desired amino acids. The reactions generally proceeded in good stereoselectivitities (75-95% ee/de) and yields (70-90%), making these optically pure amino acids available in large scale practical for the synthesis of peptides and other studies. (C) 1997 Elsevier Science Ltd.