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In the context of the use of carbohydrates obtained from agricultural crops, the search for amphiphilic derivatives is one of the most developed aspects. Indeed, due to the high polarity and the functional richness of sugars, many different structures can be targeted, with a wide range of physicochemical properties, either for large scale products of industrial interest, or for fine applications at the chemistry-biology interface. Among carbohydrates arising from agricultural resources, sucrose is especially interesting because of its very large production scale in the world (ca. 160Mt/year, ca. 20Mt/year of which in the European Community). Here, we describe the research accomplished in our group dealing with the synthesis and the study of the properties of amphiphilic derivatives prepared from sucrose as well as from another very available disaccharide, isomaltulose.

Derivatization of carbohydrates is of considerable interest since the derivatives can be used for structural studies in the field of mass spectrometry. We report here the synthesis of a series of sterically crowded derivatives of various linkage and stereo-isomeric glucose-glucose disaccharides with the impetus being to understand the effect of these derivatized groups on fragmentation of the glycosidic bond and the development of methodology for discernment of the anomeric configuration. The synthesis of per-alkylated (methyl, ethyl, propyl, butyl, and pentyl), per-esterified (acetyl, pivaloyl, mesitoyl), and per-silylated (tert-butyl-dimethyl silyl) glucose--glucose disaccharide derivatives has been reported.

Glycosidation of saccharides combines the essential characteristics of two major renewable classes, viz. triglycerides and carbohydrates, leading to biofriendly surfactants and emulsifiers. The development of the alkylglycosides derived from reducing disaccharides has lagged, because no efficient synthesis was available. We have found that ordered mesoporous materials of the MCM-41 type are active and selective catalysts for the glycosidation of disaccharides containing fructose at the reducing end, i.e., isomaltulose, lactulose and leucrose. No alcoholysis or hydrolysis of the glycosidic bond was observed, demonstrating the mildness of the MCM-41 catalyst. Leucrose was found to be less reactive than the two other disaccharides, in accordance with the absence of furanose forms in leucrose., (Copyright 2002 Elsevier Science Ltd.)

Not only sucrose but the five isomeric alpha-D-glucosyl-D-fructoses trehalulose, turanose, maltulose, leucrose, and palatinose are utilized by Klebsiella pneumoniae as energy sources for growth, thereby undergoing phosphorylation by a phosphoenolpyruvate-dependent phosphotransferase system uniformly at 0-6 of the glucosyl moiety. Similarly, maltose, isomaltose, and maltitol, when exposed to these conditions, are phosphorylated regiospecifically at O-6 of their non-reducing glucose portion. The structures of these novel compounds have been established unequivocally by enzymatic analysis, acid hydrolysis, FAB negative-ion spectrometry, and 1H and 13C NMR spectroscopy. In cells of K. pneumoniae, hydrolysis of sucrose 6-phosphate is catalyzed by sucrose 6-phosphate hydrolase from Family 32 of the glycosylhydrolase superfamily. The five 6'-O-phosphorylated alpha-D-glucosyl-fructoses are hydrolyzed by an inducible (approximately 49-50 Kda) phospho-alpha-glucosidase from Family 4 of the glycosylhydrolase superfamily.

A novel approach has been developed for the synthesis of methyl alpha-isomaltoside (10), comprising, as the first step, electrochemical conversion of the hydroxyl groups of methyl alpha-D-glucopyranoside into the corresponding anions. The anions subsequently react with tetra-O-acetyl-alpha-D-glucopyranosyl bromide to give methyl 2',3',4',6'-tetra-O-acetyl-alpha-isomaltoside (8) as the main product, O-deacetylation of which affords 10. The glycosidation proceeds under complete stereochemical control.

Enantioselective and diastereoselective alpha-D-glucosylation of 2,3-O-isopropylidene-erythritol was observed in transglucosylation with a synthetic donor using three kinds of immobilized isomaltulose-producing microorganisms. Several related compounds, including an 2,3-O-isopropylidenated aldotetrose dimethyl dithioacetal and an aldotetronic acid ester were also glucosylated in moderate or good yield, depending on the microorganism utilized. Steric as well as functional group factors are discussed in relation to the substrate specificity of the glucosyl acceptor.

The syntheses of several alpha-linked thioglycosidic disaccharides are described, including thiokojibiose octaacetate (1), thionigerose (2), and thioisomaltose (3). The title compounds were synthesized by coupling 2,3,4,6-tetra-O-acetyl-1.5-acetyl-1-thio-alpha-D-glucopyranose (4) with either 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethylsulfonyl-beta-D-manno pyr anose (7), 1,2:5,6-di-O-isopropylidene-3-O-trifluoromethylsulfonyl-alpha-D-++ +allofuranose (15), or methyl 2,3,4-tri-O-acetyl-6-deoxy-6-iodo-alpha-D-glucopyranoside (17), respectively. Thiokojibiose octaacetate in turn was converted to 3,4,6-tri-O-acetyl-2-S-(2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl)-2 -thio-alpha-D-glucopyranosyl bromide (9), which was used to obtain several related disaccharides and one trisaccharide. All of the compounds, including thiomaltose and thiotrehalose, which were resynthesized by known methods, were tested for their anti-HIV activity in either CEM or MT-2 cells. Anti-HIV activity was noted only with thiokojibiose octaacetate and its 1-thio analogue (14), which had IC50 values of 51 and 48 micrograms/mL in CEM cells, respectively.

Dispirodioxanyl pseudotetrasaccharides 6-O-alpha-D-glucopyranosyl-alpha-D-fructofuranose 6-O-alpha-D-glucopyranosyl-beta-D-fructofuranose 1,2':2,1'-dianhydride, 5-O-alpha-D-glucopyranosyl-alpha-D-fructopyranose 5-O-alpha-D-glucopyranosyl-beta-D-fructopyranose 1,2':2,1'-dianhydride, 4-O-alpha-D-glucopyranosyl-alpha-D-fructofuranose 4-O-alpha-D-glucopyranosyl-beta-D-fructopyranose 1,2':2,1'-dianhydride, 4-O-beta-D-galactopyranosyl-alpha-D-fructofuranose 4-O-beta-D-galactopyranosyl-beta-D-fructopyranose 1,2':2,1'-dianhydride, and 3-O-alpha-D-glucopyranosyl-alpha-D-fructofuranose 3-O-alpha-D-glucopyranosyl-beta-D-fructofuranose 1,2':2,1'-dianhydride were respectively obtained, on a preparative scale, by dissolution of the isomeric glycosylfructoses palatinose, leucrose, maltulose, lactulose, and turanose in anhydrous hydrogen fluoride. The reaction, involving selective protonation at the free anomeric position of the fructose unit, was extended to the preparation of the pseudotrisaccharides 6-O-alpha-D-glucopyranosyl-alpha-D-fructofuranose beta-D-fructopyranose 1,2':2',1-dianhydride from palatinose and fructose, and to its 3-O-, 4-O-, and 4'-O-glucosyl analogues using turanose and maltulose as the disaccharide precursor. The cross-reactions of palatinose with maltulose and with leucrose resulted in the preparation of 6-O-alpha-D-glucopyranosyl-alpha-D-fructofuranose 4-O-alpha-D-glucopyranosyl-beta-D-fructopyranose 1,2':2,1'-dianhydride and 6-O-alpha-D-glucopyranosyl-alpha-D-fructofuranose 5-O-alpha-D-glucopyranosyl-beta-D-fructopyranose 1,2':2,1'-dianhydride, respectively.

Selective activation of the ketose unit in the isomeric glycosylfructoses, palatinose, leucrose, maltulose, turanose and lactulose, with pyridinium poly(hydrogen fluoride) resulted in the almost quantitative formation of glycosylated difructose dianhydrides. The reaction preferentially involves a reactive fructofuranosyl oxocarbenium ion and is subject to stereoelectronic control. The relative amounts of isomeric spirodioxanyl oligosaccharides obtained within a series was shown to depend on the reaction conditions, especially on the hydrogen fluoride-pyridine ratio. Using suitable concentrations of hydrogen fluoride in pyridine, the reaction was easily directed to the formation of the kinetic difuranosyl or thermodynamic pyranosyl derivatives. More rigorous conditions resulted in the specific hydrolysis of one glycosidic bond in the tetrasaccharides derived from palatinose, leucrose and turanose, to yield spirodioxanyl trisaccharides.