Manuel Angulo

Completely regioselective synthesis of 5- and 6- amino and fluoro-hexofuranoses via cyclic sulphates

Abstract The nucleophilic opening of new and previously described 5,6- and 3,5-glucohexofuranose cyclic sulphates is a regioselective and efficient way to prepare 6- and 5-azido(amino)- and 6- and 5- fluoro-aldofuranose derivatives ( d -gluco and l -ido configurations).

Cyclic sulfates in the regioselective synthesis of 5- and 6-amino and 5- and 6-fluorohexofuranoses

Abstract Cyclic sulfates of 5,6- and 3,5- d -glucofuranose were used to prepare 6- and 5-azido (amino) and 6- and 5-fluoro derivatives of 1,2- O -isopropylidenehexofuranoses ( d - gluco and l - ido configurations). The reactions were completely regioselective and, in the case of stereogenic centers (substitution at C-5), completely stereoselective.

Tandem ATRP/Diels–Alder synthesis of polyHEMA-based hydrogels

The efficient, controlled polymerization of a batch of new poly(hydroxyethyl methacrylate-co-furfuryl methacrylate)s, [poly(HEMA-co-FMA)], of various compositions was achieved using atom transfer radical polymerization (ATRP) in methanol. When the FMA composition did not exceed the 10 mol% ratio, the evolution of molecular weight with conversion was linear, and polydispersities were around 1.1 for polymerization reactions at 15 °C and around 1.3–1.4 at 25 °C, indicating good control over the polymerization process. HEMA-based hydrogels were obtained by means of the Diels–Alder reaction between poly(HEMA-co-FMA) and an hydrophilic bisdienophile. Gelification was monitored by diffusion-filtered 1H NMR and solution 1H NMR spectroscopy. Modulated temperature differential scanning calorimetry (MTDSC) suggests the thermo-reversibility of the Diels–Alder coupling reaction of HEMA polymeric networks. Rheological studies showed that the linear viscoelasticity functions of hydrogels were influenced by the chemical composition.

Alkoxyamine-cyanoborane adducts: efficient cyanoborane transfer agents

We report the synthesis of the hitherto unknown zwitterionic alkoxyamino cyanoboranes by reduction of O-alkyloximes with sodium cyanoborohydride; unprecedented cyanoboronated N-alkoxyformamidines were also isolated as by-products. Boronated alkoxyamines were found to be efficient cyanoborane transfer agents towards more basic amines, including aminosugars; they were also successfully transformed into neoglycoconjugates by the neoglycorandomization reaction with reducing sugars.

Synthesis, Biological Evaluation, WAC and NMR Studies of S-Galactosides and Non-Carbohydrate Ligands of Cholera Toxin Based on Polyhydroxyalkylfuroate Moieties

The synthesis of several non-carbohydrate ligands of cholera toxin based on polyhydroxyalkylfuroate moieties is reported. Some of them have been linked to D-galactose through a stable and well-tolerated S-glycosidic bond. They represent a novel type of non-hydrolyzable bidentate ligand featuring galactose and polyhydroxyalkylfuroic esters as pharmacophoric residues, thus mimicking the GM1 ganglioside. The affinity of the new compounds towards cholera toxin was measured by weak affinity chromatography (WAC). The interaction of the best candidates with this toxin was also studied by saturation transfer difference NMR experiments, which allowed identification of the binding epitopes of the ligands interacting with the protein. Interestingly, the highest affinity was shown by non-carbohydrate mimics based on a polyhydroxyalkylfuroic ester structure.

Reactions of Per-O-Acetylglucosyl Isothiocyanate with Enamines. A Route for the Synthesis of Pyrimidine Nucleosides

Abstract The reaction of 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocyanate with enamines in basic medium to form the glucosylthioamides 9-16, the glucosylthiourea 17, and the nucleoside analogue 18 is reported. The N-halogenophenyl-(1-3, 5-7) and the N-(3,4-dimethoxybenzyl)-(4,8) enaminoesters or enaminones were prepared as precursors for 9-18. The treatment of several of the prepared glucosylthioamides with thiophosgene yields dithioxopyrimidine nucleosides (19-22) with the sugar ring on position 3 of the heterocycle. Glucosylamides are isolated as byproducts. The enamino moieties of the prepared glucosylthioamides and glycosylamides have the EEE configuration and the thioamide or amide bond the Z, anti geometry.

Stoppering/unstoppering of a rotaxane formed between an N-hetorycle ligand containing surfactant: β-cyclodextrin pseudorotaxane and pentacyanoferrate(II) ions

The assembly of a surfactant-based rotaxane by adding the labile aquopentacyanoferrate(II) ion to the previously formed pseudorotaxane between the surfactant 11-(isonicotinoyloxy)-N,N,N-triethyl-1-undecanaminium bromide and β-cyclodextrin was investigated by 1H NMR and kinetic measurements. NMR spectroscopy has showed that the rotaxane can be formed through two different mechanisms. The rotaxane can be unstoppered by using the pyridine ligand substitution reaction by the high-field cyanide ligand. In this work a new method is developed for the preparation of several new surfactant-based rotaxanes by changing the hydrophilic and hydrophobic regions of the surfactants and the nature of the macrocycle.