alpha-ketocarbonyl peptides: A general approach to reactive resin-bound intermediates in the synthesis of peptide isosteres for protease inhibitor screening on solid support

alpha -Ketocarbonyl peptides were generated from peptide precursors on soli d support via a metal-ion-catalyzed transamination. The reaction proceeded to completion within 2 h with glyoxylate as electrophile and copper(II) ion s as catalyst in an aqueous acetate buffer at pH 5.5-6.0. The variety of na turally occurring alpha -amino acid substrates gave rise to a diverse set o f differentially functionalized ketones. The highly reactive terminal ketoc arbonyls were prone to aldol-type dimerization and could be transferred int o stable moieties by oxime formation, reduction to the alcohol, or reductiv e amination, respectively. The alpha -ketocarbonyl peptides were efficient in nucleophilic addition of C-nucleophiles such as phosphono-ylides and all ylsilanes.