Amino acids and peptides. XLIX. Synthesis of γ-2-adamantylglutamate and its evaluation for peptide synthesis

2-Adamantyl ester was examined for the selective protection of the γ-carboxyl function of the Glu residue, with the aim of preventing side reactions during peptide synthesis and increasing the solubility in organic solvents of peptide intermediates containing the Glu residue. Z-Glu(O-2-Ada)-oBzl was synthesized from Z-Glu-OBzl and adamantan-2-ol with the aid of dicyclohexylcarbodiimide (DCC) and 4-N,N-dimethylaminopyridine (DMAP) in AcOEt. The 2-adamantyl ester group was stable to TFA, 20% piperidine/DMF and 10% Et 3 N/DMF up to 24h h and was easily removed by MSA, I M TFMSA-thioanisole in TFA, and HF. Therefore, H-Glu-(O-2-Ada)-OH could be applied for peptide synthesis in both solution and solid phase methods in combination with a Boc or Fmoc group as the Na-protecting group. Boc-Glu(O-2-Ada)-OH was successfully employed for the synthesis of Bz-Ile-Glu-Gly-Arg-CH 2 Cl, an irreversible inhibitor of factor Xa.