New Enzymatic Methods for the Selective Functionalization of Carbohydrate Derivatives

Abstract

New enzymatic methods are reported to carry out chiral pool syntheses starting with saccharides, to develop a chemo-enzymatic method for the de novo synthesis of enantiomerically enriched monosaccharides and to establish new enzymatic techniques for the chemo- and regioselective functionalization of carbohydrates, peptides and complex glycoconjugates. The pheromone (+)-exo-brevicomin was synthesized by a chemoenzymatic chiral pool synthesis from carbohydrates, employing an aldolase-catalyzed aldol reaction as key step. Enantiomerically enriched furylalkylcarbinols, which can be transformed to L-hexoses like L-aculose and L-cinerulose A, were generated by means of a penicillin G acylase-mediated enantioselective hydrolysis of the corresponding phenylacetates. The enzymes penicillin G acylase and acetyl esterase from orange peel were successfully used to effect the chemo- and regioselective removal of phenylacetyl and acetyl blocking groups from differently protected carbohydrates. The N-terminal deprotection of peptides was achieved via hydrolysis of phenylacetamides, employing again penicillin G acylase as the biocatalyst. The C-terminal carboxyl function of peptides and complex, acid- and base-labile O-glycopeptides was carried out by the lipase-mediated hydrolysis of heptyl esters.