Expedient Synthesis of Core Disaccharide Building Blocks from Natural Polysaccharides for Heparan Sulfate Oligosaccharide Assembly

The complex sulfation motifs of heparan sulfate glycosaminoglycans (HS GAGs) play critical roles in many important biological processes. However, an understanding of their specific functions has been hampered by an inability to synthesize large numbers of diverse, yet defined, HS structures. Here, we describe a new approach to access the four core disaccharides required for HS/heparin oligosaccharide assembly from natural polysaccharides. The use of disaccharides as minimal precursors rather than monosaccharides greatly accelerates the synthesis of HS GAGs, providing key disaccharide and tetrasaccharide intermediates in about half the number of steps compared to traditional strategies. Rapid access to such versatile intermediates will enable the generation of comprehensive libraries of sulfated oligosaccharides for unlocking the ‘sulfation code’ and understanding the roles of specific GAG structures in physiology and disease

Expedient Synthesis of Core Disaccharide Building Blocks from Natural Polysaccharides for Heparan Sulfate Oligosaccharide Assembly

The complex sulfation motifs of heparan sulfate glycosaminoglycans (HS GAGs) play critical roles in many important biological processes. However, an understanding of their specific functions has been hampered by an inability to synthesize large numbers of diverse, yet defined, HS structures. Here, we describe a new approach to access the four core disaccharides required for HS/heparin oligosaccharide assembly from natural polysaccharides. The use of disaccharides as minimal precursors rather than monosaccharides greatly accelerates the synthesis of HS GAGs, providing key disaccharide and tetrasaccharide intermediates in about half the number of steps compared to traditional strategies. Rapid access to such versatile intermediates will enable the generation of comprehensive libraries of sulfated oligosaccharides for unlocking the ‘sulfation code’ and understanding the roles of specific GAG structures in physiology and disease

Chemistry of 2-nitroglycals: a one-pot three-component stereoselective approach toward 2-C-branched O-galactosides

A convenient one-pot three-component approach for the synthesis of 2-C-branched O-glycosides has been developed from 2-nitroglycals. These 2-C-branched sugars have been shown to be precursors for a variety of biologically and synthetically relevant molecules

Influence of Side Chain Conformation and Configuration on Glycosyl Donor Reactivity and Selectivity as Illustrated by Sialic Acid Donors Epimeric at the 7‑Position

Two <i>N</i>-acetyl 4<i>O</i>,5<i>N</i>-oxazolidinone-protected sialyl thioglycosides epimeric at the 7-position have been synthesized and their reactivity and stereoselectivity in glycosylation reactions have been compared. It is demonstrated that the natural 7<i>S</i>-donor is both more reactive and more α-selective than the unnatural 7<i>R</i>-isomer. The difference in reactivity is attributed to the side chain conformation and specifically to the proximity of O7 to the anomeric center. In the natural <i>7S</i>-isomer, O7 is closer to the anomeric center than in its unnatural 7<i>R</i>-epimer and, therefore, better able to support incipient positive charge at the locus of reaction. The difference in selectivity is also attributed to the side conformation, which in the unnatural 7<i>R</i>-series is placed perpendicularly above the α-face of the donor and so shields it to a greater extent than in the 7<i>S</i>-series. These observations are consistent with earlier conclusions on the influence of the side chain conformation on reactivity and selectivity derived from conformationally locked models in the glucose and galactose series and corroborate the suggestion that those effects are predominantly stereoelectronic rather than torsional. The possible relevance of side chain conformation as a factor in the influence of glycosylation stereoselectivity by remote protecting groups and as a control element in enzymic processes for glycosidic bond formation and hydrolysis are discussed. Methods for assignment of the anomeric configuration in the sialic acid glycosides are critically surveyed

The FAD2 Gene in Plants: Occurrence, Regulation, and Role

Vegetable oils rich in oleic acid are more desirable than oils rich in polyunsaturated and saturated fatty acids. The biological switch of oleic acid to linoleic acid is facilitated by fatty acid desaturase 2 enzyme that is further classified into FAD2-1, FAD2-2, FAD2-3, and FAD2-4. The genes coding these enzymes have high sequence similarity, but differ mostly in their expression patterns. The seed-type FAD2 genes had evolved independently after segregation by duplication from constitutively expressed FAD2 genes. Temperature, light and wounding effectively regulate FAD2 expression in plants. FAD2 genes are expressed differently in different tissues of the plant, and the over-expression of FAD2 modifies physiological and vegetative characteristics. The activity of FAD2 leads to an increase in the content of dienoic fatty acids, and hence increases the resistance toward cold and salt stress. The thorough study of the FAD2 gene is important for understanding the expression, regulation and mechanism that will help in improving the quality of oil and stress resistance in plants

Probing the Influence of Protecting Groups on the Anomeric Equilibrium in Sialic Acid Glycosides with the Persistent Radical Effect

A method for the investigation of the influence of protecting groups on the anomeric equilibrium in the sialic acid glycosides has been developed on the basis of the equilibration of <i>O</i>-sialyl hydroxylamines by reversible homolytic scission of the glycosidic bond following the dictates of the Fischer–Ingold persistent radical effect. It is found that a <i>trans</i>-fused 4<i>O</i>,5<i>N</i>-oxazolidinone group stabilizes the equatorial glycoside, i.e., reduces the anomeric effect, when compared to the 4<i>O</i>,5<i>N</i>-diacetyl protected systems. This effect is discussed in terms of the powerful electron-withdrawing nature of the oxazolidinone system, which in turn is a function of its strong dipole moment in the mean plane of the pyranose ring system. The new equilibration method displays a small solvent effect and is most pronounced in less polar media consistent with the anomeric effect in general. The unusual (for anomeric radicals) poor kinetic selectivity of anomeric sialyl radicals is discussed in terms of the planar π-type structure of these radicals and of competing 1,3-diaxial interactions in the diastereomeric transition states for trapping on the α- and β-faces of the radical

Aza-Claisen rearrangement of 2-C-hydroxymethyl glycals as a versatile strategy towards synthesis of isofagomine and related biologically important azasugars

Synthesis of isofagomine has been achieved by implementation of aza-Claisen rearrangement of 2-C-hydroxymethyl glycals as a key step. The above rearrangement has also been utilized in the synthesis of biologically important polyhydroxylated piperidine frameworks such as isogalactofagomine, ent-isogalactofagomine and their analogues and some other azasugars as glycosidase inhibitors

A concise route to (-)-shikimic acid and (-)-5-epi-shikimic acid, and their enantiomers via Barbier reaction and ring-closing metathesis

A simple route for the synthesis of naturally occurring (-)-shikimic acid, (-)-5-epi-shikimic acid, and their enantiomers from D-ribose-derived enantiomeric aldehydes 8a and 8b by employing Barbier reaction and ring-closing metathesis as key steps has been developed

Acetyl chloride-silver nitrate-acetonitrile: a reagent system for the synthesis of 2-nitroglycals and 2-nitro-1-acetamido sugars from glycals

A new reagent system comprising acetyl chloride, silver nitrate, and acetonitrile has been developed for the synthesis of 2-nitroglycals from the corresponding glycals. Under certain conditions, the formation of 2-nitro-1-acetamido sugars has also been observed. In addition, a few other non-carbohydrate-derived olefins also gave the corrresponding conjugated nitroolefins

Synthesis of 2‑Nitroglycals from Glycals Using the Tetrabutylammonium Nitrate–Trifluoroacetic Anhydride–Triethylamine Reagent System and Base-Catalyzed Ferrier Rearrangement of Acetylated 2‑Nitroglycals

A reagent system comprising tetrabutylammonium nitrate–trifluoroacetic anhydride–triethylamine has been developed for the synthesis of 2-nitroglycals from various protected glycals. The base-catalyzed Ferrier rearrangement on tri-<i>O</i>-acetylated 2-nitroglycals has been reported for the first time. Reactivity of these nitroacetates and associated selectivity has been examined, and some of the products have been converted into 2,3-diamino-2,3-dideoxyglycosides and methyl <i>N</i>-acetyl-d-lividosaminide