Carlos Mayato

Conformational Domino Effect in Saccharides : A Prediction from Alkyl β-(1→6)-Diglucopyranosides

A series of alkyl beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosides, containing nonchiral and chiral aglycons, were synthesized and analyzed by NMR and CD. The results, collected from four sets of disaccharides, demonstrated that the rotational properties of the interglycosidic linkage depend on the structural natures of both the aglycon and the solvent. Stereoelectronic and steric factors explain this rotational dependence, the gauche- trans (gt) rotamer being the most stable. Furthermore, correlations between Tafts steric parameters or between the pKa values of the alkyl substituent (aglycon) versus corresponding rotamer populations were observed. These results point to a natural conformational domino effect in oligosaccharides, where the conformational properties of each (1-->6) interglycosidic linkage will depend on the structure of the previous residue or its aglycon. In addition, a very weak rotational population dependence of the hydroxymethyl group at residue II on the aglycon at residue I was observed. The population of the gauche- gauche (gg) rotamer decreased, and that of gt increased as the Tafts steric parameters of the remote aglycon increased, independently of the disaccharide series and of the solvent.

Comparison of the conformational properties of carbasugars and glycosides: the role of the endocyclic oxygen

A series of carbasugars were prepared and their conformational properties studied by means of NMR spectroscopy. The results were compared to those previously found for O-, S-, and C-β-glycoside analogs. While the rotational populations of the hydroxymethyl group in O-, S-, and C-glycosides are known to depend on the structural nature of their aglycon, in carbasugars it proved to be independent of the pseudo-aglycon. This result confirms that endocyclic oxygen is necessary for the observed relationship between the structure of the aglycon and the rotational populations of the hydroxymethyl group, and indicates that the stereoelectronic exo-anomeric effect is mainly responsible for such conformational dependence.

Synthetic menthyl α/β-(1→6)-diglucopyranosides-induced cell death in human leukemia cells is dependent on caspases

A series of alkyl α/β-(1→6)-diglucopyranosides 1-12 were synthesized and assessed for cytotoxicity against HL-60, U937, Molt-3 and MCF-7 cancer cell lines. The menthyl derivatives displayed strong cytotoxic properties showing IC(50) values between 6 and 16 μM. Furthermore, we demonstrated that the selected synthetic (+)-menthyl β-(1→6)-diglucopyranoside 5 induces apoptotic cell death in human leukemia cells through a mechanism that involves activation of multiple caspases. Cell death was completely prevented by the non-specific caspase inhibitor z-VAD-fmk and found to be associated with the release of cytochrome c, an increase in the expression of Bax levels and a decrease in the generation of reactive oxygen species.