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 sy nthesized 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 azida tion of the alpha-position of the resulting product was followed by hy drolysis, hydrogenation and finally deprotection of the phenol group t o 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 f or the synthesis of peptides and other studies. (C) 1997 Elsevier Scie nce Ltd.