STUDIES RELATED TO A CONVERGENT FRAGMENT-COUPLING APPROACH TO PEPTIDE-SYNTHESIS USING THE KAISER OXIME RESIN

In our efforts to synthesize the beta-amyloid protein of Alzheimer's disease and other amyloid-forming peptides, we have used a convergent solid-phase fragment coupling strategy employing the p-nitrobenzophenone oxime resin developed by E. T. Kaiser.1,2 The Kaiser oxime resin's lability to a variety of nucleophiles adds flexibility to the synthesis. We report improved procedures for the preparation and coupling of protected fragments on the Kaiser oxime resin.3 Rearrangements which can occur during the synthesis, cleavage, and coupling of protected fragments have been characterized and steps have been taken to eliminate or minimize these side reactions. In addition, we report a procedure for the preparation of C-terminal primary amides using the Kaiser oxime resin.