Methyl α-D-galactopyranosyl-(1→3)-ß-D-galactopyranoside and methyl ß-D-galactopyranosyl-(1→3)-ß-D-galactopyranoside: Glycosidic linkage conformation determined from MA'AT analysis.

MA'AT analysis has been applied to two biologically-important O-glycosidic linkages in two disaccharides, α-D-Galp-(1→3)-ß-D-GalpOMe (3) and ß-D-Galp-(1→3)-ß-D-GalpOMe (4). Using density functional theory (DFT) to obtain parameterized equations relating a group of trans-O-glycosidic NMR spin-couplings to either phi (ϕ') or psi (ψ'), and experimental 3JCOCH, 2JCOC, and 3JCOCC spin-couplings measured in aqueous solution in 13C-labeled isotopomers, probability distributions of ϕ' and ψ' in each linkage were determined and compared to those determined by aqueous 1-µs molecular dynamics (MD) simulation. Good agreement was found between the MA'AT and single-state MD conformational models of these linkages for the most part, with modest (approximately <15°) differences in the mean values of ϕ' and ψ', although the envelope of allowed angles (encoded in circular standard deviations or CSDs) is consistently larger for ϕ' determined from MA'AT analysis than from MD for both linkages. The MA'AT model of the α-Galp-(1→3)-ß-Galp linkage agrees well with those determined previously using conventional NMR methods (3JCOCH values and/or 1H-1H NOEs), but some discrepancy was observed for the ß-Galp-(1→3)-ß-Galp linkage, which may arise from errors in the conventions used to describe the linkage torsion angles. Statistical analyses of X-ray crystal structures show ranges of ϕ' and ψ' for both linkages that include the mean angles determined from MA'AT analyses, although both angles adopt a wide range of values in the crystalline state, with ϕ' in ß-Galp-(1→3)-ß-Galp linkages showing greater-than-expected conformational variability.

Straightforward synthesis of the hexasaccharide repeating unit of the O-specific polysaccharide of Salmonella arizonae O62.

A straightforward synthesis of the hexasaccharide repeating unit of the O-specific polysaccharide of Salmonella arizonae O62 was achieved in very good yield applying sequential glycosylation strategy. Successful regioselective glycosylation of the di-hydroxylated L-rhamnose moiety allowed achieving the desired compound in minimum number of synthetic steps. TEMPO catalyzed and [bis(acetoxy)iodo]benzene (BAIB) mediated late stage regioselective oxidation of a primary hydroxyl group into carboxylic acid was achieved in the hexasaccharide derivative. The glycosylation steps were high yielding with high stereochemical outcome. The desired hexasaccharide was obtained in 7% over all yield in fourteen steps starting from suitably functionalized monosaccharide intermediates.

Straightforward synthesis of the pentasaccharide repeating unit of the cell wall O-antigen of Escherichia coli O43 strain.

A concise synthetic strategy has been developed for the synthesis of the pentasaccharide repeating unit of the cell wall O-antigen of Escherichia coli O43 strain involving stereoselective ß-D-mannosylation and α-L-fucosylation using corresponding trichloroacetimidate intermediates and perchloric acid supported over silica (HClO4-SiO2) as glycosylation promoter. The yield and stereoselectivity of the glycosylations were very good.

Synthesis of the tetrasaccharide repeating unit of the O-specific polysaccharide of Azospirillum doebereinerae type strain GSF71T using linear and one-pot iterative glycosylations.

A straightforward synthetic strategy was developed for the synthesis of the tetrasaccharide repeating unit corresponding to the O-specific polysaccharide of Azospirillum doebereinerae type strain GSF71T in a very good yield adopting sequential glycosylation followed by removal of the p-methoxybenzyl (PMB) group in the same pot. Further, the synthetic strategy was modified by carrying out three stereoselective iterative glycosylations followed by in situ removal of the PMB group in one pot. The stereochemical outcome of the newly formed glycosidic linkages was excellent using thioglycoside derivatives as glycosyl donors and a combination of N-iodosuccinimide (NIS) and perchloric acid supported on silica (HClO4-SiO2) as the glycosyl activator.

Conformational disorder in the crystal structure of methyl 2-acetamido-2-deoxy-ß-D-glucopyranosyl-(1→4)-2-acetamido-2-deoxy-ß-D-glucopyranoside (methyl ß-chitobioside) methanol monosolvate.

Methyl 2-acetamido-2-deoxy-ß-D-glucopyranosyl-(1→4)-2-acetamido-2-deoxy-ß-D-glucopyranoside (methyl ß-chitobioside), (IV), crystallizes from aqueous methanol at room temperature to give a structure (C17H30N2O22·CH3OH) containing conformational disorder in the exocyclic hydroxymethyl group of one of its ßGlcNAc residues. As observed in other X-ray structures of disaccharides containing ß-(1→4) O-glycosidic linkages, inter-residue hydrogen bonding between O3H of the ßGlcNAc bearing the OCH3 aglycone and O5 of the adjacent ßGlcNAc is observed based on the 2.79 Šinternuclear distance between the O atoms. The structure of (IV) was compared to that determined previously for 2-acetamido-2-deoxy-ß-D-glucopyranosyl-(1→4)-2-acetamido-2-deoxy-ß-D-glucopyranose (ß-chitobiose), (III). The O-glycosidic linkage torsion angles, phi (φ) and psi (ψ), in (III) and (IV) differ by 6-8°. The N-acetyl side chain conformation in (III) and (IV) shows some context dependence, with the C1-C2-N-Ccar torsion angle 10-15° smaller for the ßGlcNAc residue involved in the internal O-glycosidic linkage. In (IV), conformational disorder is observed in the exocyclic hydroxymethyl (-CH2OH) group in the ßGlcNAc residue bearing the OCH3 aglycone, and a fitting of the electron density indicates an approximate 50:50 distribution of the gauche-gauche (gg) and gauche-trans (gt) conformers in the lattice. Similar behavior is not observed in (III), presumably due to the different packing structure in the vicinity of the -CH2OH substituent that affects its ability to hydrogen bond to proximal donors/acceptors. Unlike (IV), a re-examination of the previously reported electron density of (III) revealed conformational disorder in the N-acetyl side chain attached to the reducing-end ßGlcNAc residue caused by rotation about the C2-N bond.

Expeditious preparation of 1,6-anhydro-1-thio-ß-d-hexopyranose derivatives.

A convenient reaction condition has been developed for the preparation of 1,6-anhydro-1-thio-ß-d-glycopyranose derivatives in excellent yield. The reaction condition is significantly fast, clean and can be scaled up for its use in the organic synthesis.

Synthesis of selenoglycosides and selenium linked disaccharides using reductive cleavage of diselenides.

Reduction of diselenides using a combination of hydrazine monohydrate and potassium hydroxide (KOH) followed by the treatment of the selenolate ions generated in situ with glycosyl halides under a one-pot, two-step phase transfer reaction condition resulted in the formation of beta-selenoglycosides in excellent yield. In addition, selenium linked disaccharide derivatives with beta-glycosidic linkages were also prepared by the reductive cleavage of diglycosyl diselenide derivatives in very good yield. The reaction condition is non-hazardous and high yielding for scaling up.

Disruption of redox homeostasis with synchronized activation of apoptosis highlights the antifilarial efficacy of novel piperine derivatives: An in vitro mechanistic approach.

A series of novel piperine derivatives were synthesized with high yield and were evaluated for its antifilarial potential against the bovine filarial parasite Setaria cervi. Among 21 (3a-3u) compounds screened, three of them (3k, 3l, 3s) showed significant potential against all the developmental stages (oocytes, microfilariae and adult) of the filarial worm in time and dose dependent manner. 3l showed the highest efficacy among the selected three compounds. These three compounds were further evaluated for both in vitro and in vivo toxicity analyses which further fortified the benign nature of the selected compounds. The antifilarial activities they exhibited were clearly fuelled through disparity of the internal redox homeostasis as evidenced from the alterations in the enzymatic and non-enzymatic antioxidants level which ultimately shifted towards activation of pro-apoptotic signaling cascade eventually leading to the death of the parasites. The ability of the compound 3l to bind thioredoxin reductase and CED-3 protein are the key findings of this study. The present study supported with several biological experiments is therefore a maiden report on the antifilarial effectiveness of these novel piperine derivatives.

Synthesis of a hexasaccharide repeating unit of the cell wall polysaccharide of Bifidobacterium animalis subsp. lactis LKM512.

A convergent synthesis of the hexasaccharide as its 2-aminoethyl glycoside corresponding to the repeating unit of the cell wall polysaccharide of Bifidobacterium animalis subsp. lactis LKM512 has been achieved applying a [4 + 2] glycosylation strategy. The disaccharide thioglycoside donor was prepared by combining a d-galactofuranosyl thioglycoside with another l-rhamnosyl thioglycoside acceptor. The yields of the individual glycosylation steps were highly satisfactory with excellent stereo outcome. An α-glycosidic linkage of the d-galactofuranosyl moiety in the hexasaccharide was achieved in very good yield.