Intermolecular dehydrogenative Heck reactions.

Glycals (or usually their O-substituted derivatives) are readily converted into 2,3-unsaturated glycosyl compounds with O-, C-, N-, S- or otherwise linked substituents at the anomeric position. These products have been found to be useful for a range of synthetic purposes. In particular, the C-glycosidic compounds have served as readily available starting materials for the preparation of useful non-carbohydrate compounds. While these allylic rearrangement processes are usually conducted under the influence of Lewis acid catalysts, adaptations that involve activation of the allylic substituents of the starting glycals as leaving groups under neutral conditions have been developed. General features of the reactions are described as well as applications in synthesis and extensions of the basic processes.

Substitution-with-Allylic-Rearrangement Reactions of Glycal Derivatives

Conformational analyses by molecular mechanics of two-bond linked, glucose-glucose and some glucose-fructose disaccharides are reviewed. Usually, the conformations found by diffraction studies of crystals of relevant molecules were in low-energy regions on φ,ψ surfaces computed with mm 3. However, several sucrosyl linkages had energies high above the global minimum. Also, the distributions of experimental conformations did not conform well to the energy surfaces for sucrose and, to a lesser extent, maltose. A new map for maltose, made with mm 3(92), had less low-energy area wherein crystal structures were not found, and a miniature crystal model accounts for the remaining distortions Of φ and ψ as well as the short O4…O1 distances in crystalline maltose. An internally consistent calculation of the lattice energy (−76kcalmor−1) required a dielectric constant of 2.5, and values around 3 also worked well for various intramolecular and intermolecular parameters and the φ,ψ map of maltose. The problems with sucrose were not resolved despite further study. The high molecular mechanics energy for some of the sucrosyl linkages may arise from failure to account for an overlapping exo-anomeric effect.

Exploration of disaccharide conformations by molecular mechanics

Glucosylated oligomannose N ‐linked oligosaccharides (Glc x Man 9 GlcNAc 2 where x = 1–3) are not normally found on mature glycoproteins but are involved in the early stages of glycoprotein biosynthesis and folding as (i) recognition elements during protein N ‐glycosylation and chaperone recognition and (ii) substrates in the initial steps of N ‐glycan processing. By inhibiting the first steps of glycan processing in CHO cells using the α‐glucosidase inhibitor N ‐butyl‐deoxynojirimycin, we have produced sufficient Glc 3 Man 7 GlcNAc 2 for structural analysis by nuclear magnetic resonance (NMR) spectroscopy. Our results show the glucosyl cap to have a single, well‐defined conformation independent of the rest of the saccharide. Comparison with the conformation of Man 9 GlcNAc 2 , previously determined by NMR and molecular dynamics, shows the mannose residues to be largely unaffected by the presence of the glucosyl cap. Sequential enzymatic cleavage of the glucose residues does not affect the conformation of the remaining saccharide. Modelling of the Glc 3 Man 9 GlcNAc 2 , Glc 2 Man 9 GlcNAc 2 and Glc 1 Man 9 GlcNAc 2 conformations shows the glucose residues to be fully accessible for recognition. A more detailed analysis of the conformations allows potential recognition epitopes on the glycans to be identified and can form the basis for understanding the specificity of the glucosidases and chaperones (such as calnexin) that recognize these glycans, with implications for their mechanisms of action.

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The solution NMR structure of glucosylated N-glycans involved in the early stages of glycoprotein biosynthesis and folding

High-field NMR spectroscopy of synthetic heparin-like di- and trisaccharides has afforded a complete set of inter-proton-coupling data on α-L-idopyranosyluronic acid, which have been used for conformational analysis. These data lead to the conclusion that α-L-iduronic acid may display considerable conformational freedom including 1C4, 4C1 and 2S0 (e.g. compound 1) conformers.



The 2-O-sulphate substituent at iduronic acid tends to stabilize the 1C4 conformation (e.g. compounds 2 and 4). In addition carbohydrate substituents at position 4 hinder the 4C1 conformation (e.g. compound 3a,b versus 1).



Furthermore, the conformation of α-L-idopyranosyluronic acid 2-sulphate is affected seriously by the substituent at position 2 of the non-reducing glucosamine residue. Thus the presence of an ammonium group (i.e. compound 7) leads to unexpected deformation of the 1C4 form of iduronic acid, whereas a sulphamino substituent at this position (e.g. compound 5a,b) brings about the 2S0 skew boat conformation.



The iduronic acid moiety of a trisaccharide (compound 6), which represents a part of the anti-thrombin III-binding site of heparin, shows conformational preference for the 2S0 form in aqueous solution under low ionic conditions. However, increasing the ionic strength (e.g. 3 M NaCl) causes the conformational equilibrium to incline towards the 1C4 chair conformer. This feature may be indicative for the mechanism of conformational control as exerted by the AT-III protein upon heparin binding.



Several molecular models of preferred conformers have been constructed; Nuclear Overhauser Enhancement data, exo-anomeric effect and Van der Waals interactions have been taken into account.

Conformational analysis of synthetic heparin-like oligosaccharides containing α-L-idopyranosyluronic acid†

Structure cristalline de la 2-acétamido-1-N-(l-aspart-4-oyl)-2-désoxy-β-d-glucopyranosylamine

The molecular structure of an anhydrous hydroxybisphosphonic acid was determined by X-ray diffraction techniques and compared to the corresponding hydrated crystalline form. The hydrogen bond network and intermolecular interactions show that the polar bisphosphonic group undergoes a rotation to accomodate a different distribution in the hydrophobic/polar zones observed in the crystal packing, while the rest of the amino side chain connected to the functional carbon atom has identical conformation.

The molecular structure of 4-amino 1-hydroxy butylidene-1 bisphosphonic acid (ahbbpa); an uncommon anhydrous hydroxybisphosphonic acid

Reinvestigation of the structure of (4,6-di-O-acetyl-2,3-dideoxy-α-D-erythro-hex-2-enopyranosyl)benzene, obtained by the title reaction, is described. The α anomeric configuration was clearly estab...

Danièle Avenel

Papers

Structure cristalline de la 2-acétamido-1-N-(l-aspart-4-oyl)-2-désoxy-β-d-glucopyranosylamine

The molecular structure of 4-amino 1-hydroxy butylidene-1 bisphosphonic acid (ahbbpa); an uncommon anhydrous hydroxybisphosphonic acid

Palladium-catalysed arylation of peracetylated glycals, III. Crystal structure of a by-product: mechanistic implications

Structure cristalline du méthyl-3-O-α-d-glucopyranosyl-α-d-glucopyranoside (méthyl-α-nigéroside)

Angiography contrast agents interact with serine proteinases. The molecular structure of the model system elastase/iohexol.