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

All four stereoisomers of the highly constrained aromatic α-amino acid β-isopropyl-2',6'-dimethyltyrosine have been asymmetrically synthesis on a large scale. A catalytic asymmetric Michael addition of an organocuprate to a chiral α,β-unsaturated acyloxazolidinone and subsequent direct or indirect stereoselective electrophilic azidation of the α-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 stereoselectivities (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.