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Synthesis of bacterial cell surface l-glycero-d-manno-heptose (l,d-Hep)- and d-glycero-d-manno-heptose (d,d-Hep)-containing higher carbon sugars is a challenging task. Here, we report a convenient and efficient approach for the synthesis of the l,d-Hep an

A highly regioselective synthesis of valuable gem-difluorinated C-furanosides from unprotected aldoses via a debenzylative cycloetherification (DBCE) reaction induced by diethylaminosulfur trifluoride is descibed. The scope and limitations of this DBCE reaction are described using a series of commercially available pentoses and hexoses to afford, without selective protection/deprotection sequences, the corresponding gem-difluorinated C-furanosides in moderate to good yields.

An efficient and regioselective approach for the construction of synthetically important γ-lactone glycosides is reported from unprotected aldoses through a new debenzylative lactonization (DBL) reaction. The scope and limitations of this DBL reaction are described starting from a series of commercially available hexoses (l-fucose, d-galactose, d-glucose) and pentoses (d-arabinose, d-ribose, d-lyxose, d-xylose) to afford the corresponding γ-lactones in good yields and without concomitant δ-lactone formation.

A variety of diethyl dithioacetals of sugars can be prepared in very good yields by the reaction of various monosaccharides with ethanethiol in the presence of 3 mol % bromodimethylsulfonium bromide (BDMS) at 0-5 °C. Similarly, dipropyl dithioacetal derivatives can also be obtained in good yields using propanethiol under identical reaction conditions. These dithioacetal derivatives were characterized by per-O-acetylation using silica gel-supported perchloric acid. The significant features of the present protocol are good-to-excellent yields, mild, clean, and solvent-free reaction conditions. This method is extremely suitable for the large-scale preparation of dithioacetal derivatives of various sugars.

Acetylation of the 2,3-O-isopropylidene derivative (1) of d-glyceraldehyde with hot acetic anhydride in the presence of sodium acetate give a mixture of (Z)- and (E)-enol acetates (2 and 3), together with the acetylated racemic aldehydrol (4) of 1. Likewise, the acyclic aldehydo 2,3:4,5-diisopropylidene acetals of d- and l-arabinose, d-xylose, and d-ribose underwent conversion into enol acetates, with the (Z) isomers preponderating, and convertible photochemically into the corresponding (E) isomers. Under other conditions of acetylation, the aldehydo derivatives were converted into the corresponding aldehydrol diacetates.

The C-polysaccharide is an antigen common to all known serotypes of Streptococcus pneumoniae bacteria and is a potential target for vaccine preparation. The final uncertainty in the structure of its repeating unit, a pentasaccharide phosphate containing two phosphorylcholine side chains, has been resolved by determining the configuration of ribitol. Assignment of configuration was performed by synthesis of the two trisaccharide phosphate fragments that have either D- or L-ribitol at their centers and comparison of their 1H and 13C NMR spectral data with that of the natural polysaccharide. The syntheses employed common synthons added in different orders to an asymmetrically substituted chiral ribitol derivative to obtain opposite chiralities in the ribitol segments. The data for the trisaccharide containing D-ribitol was almost identical to that of the natural material while that for the trisaccharide containing L-ribitol differed significantly. In particular, the chemical shift differences between the two protons of the primary carbons of ribitol units directly attached to the β-2-acetamido-2-deoxy-galactopyranosyl residue were 0.10, 0.12, and 0.33 ppm, in the natural polysaccharide, the D-ribitol-containing trisaccharide, and the L-ribitol-containing trisaccharide, respectively. The average difference between the 13C NMR chemical shifts of corresponding ribitol carbons from the natural polysaccharide and the D-ribitol-containing trisaccharide phosphate was 0.034 ppm. This evidence indicates that ribitol in the C-polysaccharide has the D-configuration and that a very similar mixture of conformations in the ribitol portions is present for the natural polysaccharide and the D-ribitol-containing trisaccharide phosphate.

Treatment of 2,3,4-tri-O-benzyl-5-benzylseleno-5-deoxyribose (9) with samarium(II) iodide in THF affords 2,3,4-tri-O-benzyl-5-deoxy-5-seleno-D- ribopyranose (10) in 50% isolated yield in a process most likely involving intramolecular homolytic substitutio

Eight prodrugs of L-cysteine (1a-h) were synthesized by the condensation of the sulfhydryl amino acid with naturally occurring aldose monosaccharides containing three, five, and six carbon atoms.The resulting 2-(polyhydroxyalkyl)thiazolidine-4(R)-carboxylic acids (TCAs) are capable of releasing L-cysteine and the sugars by nonenzymatic ring opening and hydrolysis.Thus, when added to rat hepatocyte preparations in vitro, these TCAs (1.0 mM) raised cellular gluthatione (GSH) levels 1.2-2.1-fold relative to controls.On the basis of this finding, the cysteine prodrugs were tested as protective agents against acetaminophen-induced hepatotoxicity in a mouse model.The TCA derived from D-ribose and L-cysteine (RibCys, 1d) showed the greatest therapeutic promise of the series, with a 100percent (12/12) survival profile compared to 17percent without treatment.However, the degree of stimulation of GSH production in rat hepatocytes by these prodrugs did not correlate with the extent of protection afforded in mice, suggesting that pharmacokinetic parameters must supervene in vivo.To evaluate the effect of increased lipid solubility, we prepared prodrugs 2a-c by using peracetylated aldehydic sugars in the condensation reaction.These compounds, however, displayed acute toxicity to mice, possibly due to liberation of the acetylated sugars themselves.Nevertheless, the efficacy of the unacetyleted TCAs, and RibCys (1d) in particular, suggests that the prodrug approach for the delivery of L-cysteine to the liver represents a viable means of augmenting existing detoxication mechanisms in protecting cells against xenobiotic substances that are bioactivated to toxic, reactive metabolites.