Resin-to-Resin Acyl- and Aminoacyl-Transfer Reactions Using Oxime Supports

Abstract

We describe a convergent approach to solid-phase synthesis in which two fragments of a molecule are synthesized on independent supports and then condensed in a key resin-to-resin transfer reaction. This approach has been utilized for the synthesis of amides and ureas by transferring acyl groups and aminoacyl groups from p-nitrophenyl(polystyrene)ketoxime resin to amino acid-functionalized Wang resins. Oxime resin-derived esters of peptides undergo transacylation to a solution-phase nucleophilic activator which then transfers the peptide to another resin bearing a nucleophilic amine terminus, resulting in amide bond formation. Likewise, oxime resin-derived carbamates, prepared from phosgenated p-nitrophenyl(polystyrene)ketoxime resin, undergo thermolytic isocyanate liberation in solution, which reacts with a second resin bearing a nucleophilic amino terminus resulting in urea bond formation.