ORGN 914 |
| The first examination of a terminal alpha-fluorovinyl trigger in an amino acid decarboxylase active site is reported. To investigate the enantiospecifity of inactivation with this new AADC trigger, an enantioselective synthesis of L-alpha-(2'Z-fluoro)vinyllysine and its D-antipode has been developed. Control of stereochemistry is achieved through introduction of the amino acid side chain via alkylation of a chiral vinylglycine-derived dienolate. Facial selectivity is conferred by a trans-2'(beta-naphthyl)-2'-propylcyclohexyl ester auxiliary, available in both antipodal forms (Comins protocol). The alkylation employs a new electrophile, N-p-methoxybenzyl-N-(2'-trimethylsilylethanesulfonyl)-4-iodobutylamine, for convergent installation of the lysine side chain. Both time-dependent enzyme kinetics and 19F NMR reveal striking differences in the behavior of these two antipodes in the lysine decarboxylase active site. The L-antipode displays time dependent inactivation, whereas the D-antipode behaves as a substrate, being completely turned over to ?-(2'Z-fluoro)vinylcadaverine. 19F NMR provides a detailed account of the inactivation with the L-antipode, and clearly shows the clean turnover of the D-antipode.
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Proteins, Peptides, Amino Acids, and Enzyme Inhibitors
8:00 AM-12:00 PM, Thursday, August 23, 2007 BCEC -- 258B, Oral
Division of Organic Chemistry |
