Amino Acids and Peptides. XLIX. Synthesis of γ-2-Adamantylglutamate and Its Evaluation for Peptide Synthesis

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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 admantan-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% Et₃N/DMF up to 24 h and was easily removed by MSA, 1 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 N^α-protecting group. Boc-Glu(O-2-Ada)-OH was successfully employed for the synthesis of Bz-Ile-Glu-Gly-Arg-CH₂Cl, an irreversible inhibitor of factor Xa.