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 solid support via a metal-ion-catalyzed transamination. The reaction proceeded to completion within 2 h with glyoxylate as electrophile and copper(II) ions as catalyst in an aqueous acetate buffer at pH 5.5-6.0. The variety of naturally occurring alpha-amino acid substrates gave rise to a diverse set of differentially functionalized ketones. The highly reactive terminal ketocarbonyls were prone to aldol-type dimerization and could be transferred into stable moieties by oxime formation, reduction to the alcohol, or reductive amination, respectively. The alpha-ketocarbonyl peptides were efficient in nucleophilic addition of C-nucleophiles such as phosphono-ylides and allylsilanes.
Papanikos
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Contribution from the Carlsberg Research Center, Department of Chemistry, Gamle Carlsberg Vej 10, DK-2500 Valby, Denmark.
Rademann
J
J
Meldal
M
M
D020650:Combinatorial Chemistry Techniques; D008670:Metals / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis*; D011480:Protease Inhibitors / Q000032:analysis*
D008670:Metals; D010455:Peptides; D011480:Protease Inhibitors