2^′, 6^′-Dimethylphenylalanine : A Useful Aromatic Amino Acid Surrogate for Tyr or Phe Residue in Opioid Peptides

Scheme 1

Synthetic route to L-Dmp and D-Dmp, (a) Me₃SnNa, DME, ice-salt bath, 2 h; (b) I₂/THF, rt, 3 h; (c) methyl 2-acetamidoacrylate/Pd(OAc)₂/Et₃N/MeCN, (2-MeC₆H₄)₃P, reflux, 24 h; (d) 1 M NaOH/dioxane, rt, 2 h; (e) H₂ (4 kgf/cm²)/10% Pd-C/AcOH, 70°C, 48 h; (f) HCl·Arg-OMe/Et₃N/DCC/HOBt/DMF, 0°C to rt, 5 h; (g) preparative HPLC; (h) concd HCl, reflux, 8 h; (i) pH 4–6/H₂O.