Solvolysis and aminolysis on peptidyl-Kaiser oxime resin assisted by Ca2+ and Eu3+: a mild procedure to prepare alpha-methyl and -ethyl esters of protected peptides

Ca2+ and Eu3+ were able to assist solvolysis on peptidyl-Kaiser oxime resin s generating alpha-methyl and -ethyl esters of protected peptides. The meth anolysis assistance was at least twice as effective as that of acetic acid, the common catalyst used in aminolysis of the ester oxime linkage. No mola r excess of Ca2+ or Eu3+ was needed to enhance this reaction efficiency. Ca 2+ also assisted aminolysis on peptidyl-Kaiser oxime resins. Solvolysis and aminolysis rates depended on the nature of the C-terminal residue attached to the resin and on the alcohol used. Both reactions were selective to the ester oxime linkage since no significant amount of secondary products, res ulting from rearrangements or simultaneous transesterification of the beta- benzyl or cyclohexyl esters, was detected in the reaction media. The alpha- methyl and -ethyl esters of Ac-Ala-Gly-X [where, X = Gly, Ala, Phe or Lys ( 2-Cl-Z)] and of Ac-Ile-Ser (Bzl)-Asp(OZ) (where, Z = Bzl or cHex) were esse ntially the only products formed in the solvolyses performed. Ac-Ile-Ser(Bn l)Asp(OcHex)Arg(HCl)-OMe and Ac-Ile-Ser(Bzl)-Asp(OcHex)Arg(HCl)-OEt were th e major products formed in the aminolysis reactions. In the presence of the metal ions, the resin-cleavage yields were > 50%. In their absence, they w ere < 15%.