ENANTIOSELECTIVE SYNTHESIS OF )-2-AMINO-3-(4-HYDROXY-3-PHOSPHONOPHENYL)PROPIONIC ACID (= 3'-PHOSPHONO-L-TYROSINE) AND ITS INCORPORATION INTO PEPTIDES

The asymmetric synthesis of derivatives of the new amino acid )-2-amin o-3-(4-hydroxy-3-phosphonophenyl)propionic acid (3'-phosphono-L-tyrosi ne; Tyr [3'-PO(OH)2]) is described. The protected amino acid 13 is obt ained via a Schollkopf synthesis by coupling of the rearranged ortho-p hosphonophenolic side chain (see Scheme 1, 6a) with the lithiated bis- lactim ether 8 of cyclo(-D-valyl-glycyl-) (see Scheme 2). The incorpor ation of the protected amino acid 14 in a biologically active dodecape ptide is successfully achieved by the [(9H-fluoren-9-yl)-methoxy]carbo nyl (Fmoc) strategy of solid-phase peptide synthesis. Differential pro tection of Tyr[3'-PO(OH)2] provides four levels of selective deprotect ion of, in the order, the N2-amino, the carboxyl (cleavage from the re sin), the phenol, and the phosphono function (-->peptide 16).