| This dissertation is about using enzymes as synthetic catalysts and using chemoenzymatic methods to study carbohydrate recognition.; The synthetic topics chosen for research were in areas where the advantages of using enzymes far outweigh the disadvantages. One such area is that of carbohydrate synthesis and another the enantioselective acylation of amines. In chapter 1, aldolases were used to synthesize nitrogen containing sugar analogs that are glycoprocessing enzyme inhibitors. In chapter 5 and 6, glycosidases and glycosyltransferases were used to prepare sialyl Lewis X (SLe{dollar}sp{lcub}rm x{rcub}{dollar}), SLe{dollar}sp{lcub}rm x{rcub}{dollar} conjugates and SLe{dollar}sp{lcub}rm x{rcub}{dollar} dimers which are selectin antagonists. In chapter 7, a protease is used to regioselectively acylate the disialoganglioside GD3 to give a melanoma specific antigen, 9-O-acetyl GD3, which was then conjugated onto a carrier protein to give an anti-cancer vaccine. Chapter 8 describes new methods and concepts for designing acylating reagents and reaction conditions for the efficient enzymatic optical resolution of amines using readily removable amine protecting groups.; Enzymes were considered not only as catalysts useful for organic synthesis but also as targets for intervention of biological processes. Chapter 1 describes the design synthesis and biological activity of cyclic imine sugars as potent inhibitors of glycosidases. Chapters 2, 3, and 4 describe efforts to analyze, inhibit, and understand glycosyltransferases: chapter 2 describes the use of electrospray mass spectrometry to solve one of the problems of studying glycosyltransferases, which is the lack of an efficient assay method; chapter 3 describes the discovery of bisphosphonates as a novel motif for glycosyltransferase inhibition; and chapter 4 describes how different divalent metal conditions can affect the activity and inhibition of galactosyltransferase. |
