SYNTHESIS OF AZAPEPTIDES BY THE FMOC TERT-BUTYL POLYAMIDE TECHNIQUE

A new synthesis of azapeptides for use in the study of a proteolytic e nzyme associated with Alzheimer's disease is described. The method uti lizes fluoren-9-ylmethoxycarbonyl (Fmoc) amino acid carbazates and hyd razides in the Fmoc/tert-butyl/polyamide technique. The preparation of these compounds is presented. Reaction of Fmoc-amino acid hydrazides with an appropriate aldehyde, followed by reduction, gave fully protec ted amino acid carbazate dipeptide synthons. These derivatives were us ed to prepare aza amino acid peptide analogues by reaction with a resi n-bound amino group, activated with bis-2,4-dinitrophenyl carbonate in the presence of a base. With this activation of the amino group, hyda ntoin is formed in a major side-reaction, but the cyclisation could be virtually eliminated by omission of the base from the activation proc edure. Upon final trifluoroacetic acid-mediated cleavage of the azapep tide, trifluoroacetylation of the N-terminal serine residue was observ ed.