387 New Methods for the Synthesis of Peptides and Glycopeptides

Friday, November 6, 2009: 4:40 PM
Angus (Camino Real Hotel)
Katja Michael , Department of Chemistry, University of Texas at El Paso, El Paso, TX
Tyrone Hogenauer , Department of Chemistry, University of Texas at El Paso, El Paso, TX
Zhefeng Cai , Department of Chemistry, University of Texas at El Paso, El Paso, TX
Clyde M. Kaneshiro , Department of Chemistry, University of Texas at El Paso, El Paso, TX
Carl Dirk , Department of Chemistry, University of Texas at El Paso, El Paso, TX
Andreas H. Franz , Department of Chemistry, University of the Pacific, Stockton, CA
Our laboratory uses novel photochemical methods to esterify, thioesterify, amidate, and to hydrolyze. The chemistry is based on the photoreactive N-acyl-7-nitroindoline moiety, which we apply to the synthesis of glycosyl amino acids, peptide-alpha-thioesters, and glycopeptides. While the nitroindoline group protects carboxylic acids as amides in the dark, it is activated with near UV light resulting in the transfer of the acyl group to a nucleophile. These acylation reactions occur under neutral conditions, which is ultimately responsible for avoiding or minimizing some problematic side reactions, e.g. the epimerization of amino acids, and aspartimide formation in the convergent N-glycopeptide synthesis. Recently, we were able to improve the photochemical method through a different order of addition of reactants, which enables us now to obtain acylation products at higher yields as well as acylation products that could previously not be synthesized due to photodecomposition. A mechanistic study with 18O-containing water helps rationalize the success of our improved method.