Chemical and enzymatic synthesis of biologically important glycolipids

Glycolipids are membrane components consisting of a lipid “tail” covalently linked to monosaccharide or polysaccharide “head” groups. Some glycolipids contain acidic carbohydrates, which have negative charges on the saccharide “head” groups. Those glycolipids can interact with proteins and also have surface-active properties. Here the preparation and properties of two different classes of acidic carbohydrate “head” groups, one based on sucrose sulfate and the other based on sialic acid, are described.; A commercial subtilisin preparation was used in pyridine to catalyze the regioselective conversion of sucrose and fatty acid vinyl esters into the 1′-O-acyl sucrose derivatives. Introduction of sulfo group onto chemically and enzymatically synthesized acyl sucrose derivatives using Pyr·SO₃ complex and nucleophilic displacement of a sucrose cyclic sulfate were investigated. This new class of sucrose-based surfactants displayed excellent surface-active properties.; [14C] Sucrose octasulfate (SOS) and unlabeled sucrose octasulfate sodium salts were synthesized to study the in tissue distribution when administered to rats by stomach tube. Additionally SOS derivatives were synthesized as potential inhibitors of fibroblast growth factor (FGF) binding to its receptors.; Ulosonic acids (Neu5Ac, KDN and KDO) are a diverse family of complex monosaccharides that serve important biological functions. Neuraminidases, KDNase and KDOase catalyze the release of ulosonic acids residing at the non reducing terminus of glycans, and this may have dramatic consequences for infection, adhesion and recognition events. Modified Neu5Ac might be used to control these biological events on a molecular level. A general method is described for diastereocontrolled synthesis of α-C-glycosides of ulosonic acids. Synthesis of ulosonic acid C-glycosides was accomplished through SmI₂ mediated desulfonation and dechlorination. Neu5Ac C-glycosides were tested as neuraminidase inhibitors. In addition, conformations of both O-glycoside and C-glycosides were examined in solution using NMR techniques.; Progress has been made towards the synthesis of the C-glycoside of the ganglioside GM₄. GM₄, the simplest of the gangliosides, is composed of sialic acid 2 → 3-linked to a galactose linked to ceramide. These gangliosides are involved in important biological events such as cell-cell adhesion, cell growth regulation or malignancy.