Aromatic glycosyl disulfide derivatives: evaluation of their inhibitory activities against Trypanosoma cruzi.

Aromatic oligovalent glycosyl disulfides and some diglycosyl disulfides were tested against three different Trypanosoma cruzi strains. Di-(ß-D-galactopyranosyl-dithiomethylene) benzenes 2b and 4b proved to be the most active derivatives against all three strains of cell culture-derived trypomastigotes with IC50 values ranging from 4 to 11 µM at 37 °C. The inhibitory activities were maintained, although somewhat lowered, at a temperature of 4 °C as well. Three further derivatives displayed similar activities against at least one of the three strains. Low cytotoxicities of the active compounds, tested on confluent HeLa, Vero and peritoneal macrophage cell cultures, resulted in significantly higher selectivity indices (SI) than that of the reference drug benznidazole. Remarkably, several molecules of the tested panel strongly inhibited the parasite release from T. cruzi infected HeLa cell cultures suggesting an effect against the intracellular development of T. cruzi amastigotes as well.

Convenient syntheses of 1,2-trans selenoglycosides using isoselenuronium salts as glycosylselenenyl transfer reagents.

Se-glycosyl-isoselenuronium salts such as three and four which can be prepared in one high-yielding step from acetohalogeno sugars proved to be convenient starting materials for the syntheses of a variety of selenoglycosides. Reaction with (ar)alkyl halides proceeds under mild conditions, in short time, at room temperature to afford the corresponding selenoglycosides in good yields. Aryl halides react to appreciable extent only if bearing activating nitro groups on the aromatic ring. Reactions with acylating reagents such as acetic anhydride and benzoyl chlorides furnished anomeric selenoesters some of which were recently proposed as starting compounds for alternative selenoglycoside syntheses. Selenodisaccharides with two different monosaccharide units could also be prepared via reactions of glycosyl-isoselenuronium salts with monosaccharide derivatives bearing primary or secondary triflate groups.

Resonance assignments of diastereotopic CH(2) protons in the anomeric side chain of selenoglycosides by means of (2) J(Se,H) spin-spin coupling constants.

Unambiguous resonance assignments of diastereotopic CH(2) protons in the anomeric side chain of nine alkyl- and aralkylselenoglycosides have been carried out on the basis of experimental CPMG-HSQMBC measurements and theoretical second order polarization propagator approach (SOPPA) calculations of geminal (77) Se-(1) H spin-spin coupling constants involving diastereotopic pro-R and pro-S protons. Theoretical conformational analyses have been performed at the MP2/6-311G** level. The conformational space of each of the selenoglycosides under study could be adequately described as a mixture of six interconverting conformers with the molar fractions depending on the nature of the side chain substituent at the selenium atom. The good agreement observed between measured and the weighted conformational averaged values of the calculated coupling constants provides a basis for reliable diastereotopic assignments in this type of carbohydrate structures.

2-Phenyl-ethyl 1-thio-ß-d-galactopyran-oside hemihydrate.

The title compound, C(14)H(20)O(5)S·0.5H(2)O, crystallizes with two organic mol-ecules and a solvent water mol-ecule in the asymmetric unit. In both mol-ecules, the hexa-pyranosyl rings adopt a slightly distorted chair conformation ((5)C(2)) with four substituents in equatorial positions and one substituent in an axial position. The main difference between the organic mol-ecules is the dihedral angle between the phenyl ring and the best plane defined by the O-C(1)-C(2)-C(3) atoms (r.m.s deviations = 0.003 and 0.043 Å) of the hexa-pyranosyl rings [47.4 (4) and 86.5 (4)°]. In the asymmetric unit, mol-ecules are linked by two strong O-H⋯O hydrogen bonds. In the crystal, the components are linked by a total of 10 distinct O-H⋯O hydrogen bonds, resulting in the formation of a two-dimensional network parallel to the ab plane.

Experimental and computational studies of nJ(77Se, 1H) selenium-proton couplings in selenoglycosides.

Selenoglycosides are important starting materials in synthetic carbohydrate chemistry and play a role in biological interactions as well. Both aspects are influenced by the conformation around the glycosidic bond. Here, we present a combined experimental and computational approach to measure and evaluate (n)J((77)Se, (1)H) coupling constants for their use in conformational analysis. The measurements were carried out using a modified CPMG-HSQMBC pulse scheme which yields pure absorption antiphase multiplets to allow accurate determination of the (n)J(XH) values regardless of the size of the proton-proton couplings. Theoretical calculations were performed at the Second-Order Polarization Propagator Approach (SOPPA) level. Population-averaged values calculated for geminal and vicinal couplings are in a good agreement with experiment indicating an adequate theoretical level of the calculations. Experimental observations and computations alike have indicated that two-bond (77)Se-(1)H couplings, (2)J((77)Se, (1)H), in a H1-C1-Se-X moiety are very sensitive to the torsion angle around the C1-Se-bond and will, therefore, be useful for conformational studies.