A Semicarbazide Resin for the Synthesis of Peptide Ketones

Significance

An efficient solid-phase synthesis of tetrapeptide ketone was achieved by use of a semicarbazide resin. Semicarbazide resin 2 was prepared by reaction of aminomethyl polystyrene 1 with tert-butyl carbazate in the presence of CDI. The reaction of 2 with phenylpropyl ketone of aspartate ester 3 gave imine 4 in 99% yield. The polymer-bound tetrapeptide ketone was prepared from imine 4 and Fmoc-protected amino acids by using the standard Fmoc peptide procedure. Release of the tetrapeptide chain from the resin with TFA-H₂O gave tetrapeptide ketone 5 in an overall yield of 75%.