Transesterification of peptide esters and peptidyl resins in methanol-containing calcium acetate

The following crude peptide derivatives obtained by thermolysin catalysis in the presence of calcium acetate, were dissolved in methanol and in methanol-containing calcium acetate to determine the possible occurrence of transesterification: Z-Asn-Leu-Gly-OEt, Boc-Asn-Leu-Gly-OEt, Moz-Asn-Leu-Gly-OBzl, Moz-Asn-Leu-Gly-OtBu, Moz-Gln-Leu-Gly-OEt, Moz-Asn-lle-Gly-OEt, and Moz-Asn-Leu-Ala-OEt. Only Z-Asn-Leu-Gly-OEt and Moz-Gln-Leu-Gly-OEt were transesterified in methanol, indicating the existence of a peptide derivative-Ca²⁺ catalytic complex that may favor the reaction. In the presence of calcium acetate, all protected peptide esters except the t-butyl esters were transesterified. The transesterification of several other di- and tripeptide derivatives of different structures in methanol-containing calcium acetate was detected by HPLC and confirmed by the isolation and characterization of some of the protected peptide methyl esters obtained. Boc-Leu-Gly- and Moz-Asn-Leu-Gly-Merrifield resin were also transesterified in these solutions.