Felicia D’Andrea

A new highly diastereoselective synthesis of epi-inositol from d-galactose

Abstract The inosose derivative 3 was obtained with high stereoselectivity by intramolecular aldol condensation of the aldohexos-5-ulose derivative 2 , and it was selectively reduced and debenzylated to give epi -inositol in high yield. The stereochemistry and the preferred conformations of compounds 3 – 7 were determined through 1D and 2D NMR experiments.

Experimental and in silico characterization of a biologically active inosose

Inositols have been recently reported to show a biological activity as inhibitors of both glycosidase and amyloid-β protein. After having harvested good crystals suitable for single crystal X-ray diffraction, we performed a comparison with the data inferred by means of a molecular dynamics simulation, based on the use of an appropriate Force Field coupled to the most performing charging scheme. This approach allowed a detailed analysis extended to ultra-fine details, such as atomic displacement parameters. It confirmed the good validity of a robust approach already tested by us in previous studies. A NMR analysis of the molecule in solution was also carried out, to compare the structural findings suggested by the X-ray analysis with the ones in solution and avoid confining them to the solid-state. In this framework, we investigated the above-mentioned inhibiting activity of a class of inososes, by means of a molecular docking investigation, which proved the suggested validity of the studied compound as inhibitor of the α-glucosidase.

Prevalence of oxetanose forms in the tautomeric equilibrium of β-hydroxy-1,5-dicarbonyl monosaccharides.

The synthesis of 4-deoxy- and 4-deoxy-4-C-methylhexos-5-uloses, starting from 4-deoxyhex-4-enopyranosides, and a nuclear magnetic resonance (NMR) study of their isomeric composition are reported. The NMR spectra show that the two δ-dicarbonyl sugars exist as two anomeric α- and β-oxetanosyl forms, derived from the hemiacetalization of the C-3 hydroxyl group with the aldehydic carbon. The observed tautomeric equilibria have been rationalized with computational calculations. Interestingly, this is the first time that dicarbonyl derivatives are mostly present in their oxetanose forms, offering a new entry into this very interesting type of scaffold.

RETRACTED: Deoxynojirimycin and its hexosaminyl derivatives bind to natural killer cell receptors rNKR-P1A and hCD69

Deoxynojirimycin (1) and two new related 4-O-hexosaminyl-containing disaccharide mimics, beta-d-TalNAc-(1-->4)-DNJ (4) and beta-d-ManNAc-(1-->4)-DNJ (5), have been studied as agonists of natural killer (NK) cell receptors. As a positive and unexpected result, DNJ (1) displayed a remarkable activation effect towards both NKR-P1A (rat) and CD69 (human) receptors, and a quite similar activity was found for 4 and 5. The synthesis of the two disaccharide mimics is based on an approach that avoids the glycosylation step using known intermediates arising from lactose. The key stage of the synthesis involves the construction of the DNJ unit through an initial C-5 oxidation of the reducing d-glucopyranosyl unit followed by a stereoselective double-reductive aminocyclization of the 1,5-dicarbonyl disaccharide intermediates.

The acetonation of methyl 5-C-methoxy-beta-D-galactopyranoside with 2,2-dimethoxypropane

Abstract The acetonation of methyl 5- C -methoxy- β - d -galactopyranoside ( 1a ), masked bis-glycoside form of l - arabino -hexos-5-ulose, with a large excess of 2,2-dimethoxypropane and catalytic amounts of p -toluenesulfonic acid gives a mixture of five acetonides. The most abundant isolated product was the mixed acetal methyl 6- O -(1–methoxy-1-methylethyl)-3,4- O -isopropylidene-5- C -methoxy- β - d –galactopyranoside (44% yield).

Synthesis of PAMAM Dendrimers Loaded with Mycophenolic Acid to Be Studied as New Potential Immunosuppressants

The terminal N-Boc protected diamino PAMAM 7 was condensed (EDC-DMAP) with two units of mycophenolic acid (MPA) giving the N-Boc protected dendron 8 in a good yield (76%). The ammonium trifluoroacetate 9 was prepared from 8 by acid treatment (TFA-THF-H2O) and was split into two equal parts. The first half was treated with di-2-pyridyl thionocarbonate (DPT) in the presence of Et3N to give the corresponding isothiocyanate 10. This was reacted with the second half of 9 providing the symmetrical dendrimer 11 (68% yield), exposing four MPA units around the thioureido-PAMAM core.

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

The intramolecular aldol condensation of aldohexos-5-ulose derivatives of the D-xylo and L-ribo stereoseries has been studied. Only one of the four possible inososes was isolated from both stereoseries in reasonable yields (30–38%). The results obtained, together with the previous findings for the L-arabino and L-lyxo stereoseries, allowed for the rationalisation of a mechanism of the reaction based on open-transition-state models and electron-withdrawing inductive effects. Complementary reductions of the intermediate inososes were possible by changing the reaction conditions, and two isomeric inositol derivatives were obtained with complete stereoselection from each inosose. The presented approach permits us to control the configuration of three out of the six stereocentres of the inositol frame and gives access to seven of the nine inositols. Noteworthy, for the D-xylo derivative, the two-step sequence (condensation followed by reduction with NaBH(OAc)3) represents the biomimetic synthesis of myo-inositol. Furthermore, the sugar-based pathway leads directly to enantiomerically pure selectively protected inositols and does not require any desymmetrisation procedure which is needed when myo-inositol and other achiral precursors are employed as starting materials. As an example of application of the method, the indirect selective protection of secondary inositols’ hydroxy functions, by placing specific protecting groups on the aldohexos-5-ulose precursor has been presented.

A New Generation of Glycoconjugated Azo Dyes Based on Aminosugars

The third generation of glycoconjugated azo dyes (GADs) was prepared linking monoazo dyes to 6-amino-6-deoxy-d-galactose or 6′amino-6′-deoxylactose through mixed amido-ester connections. The complementary conjugation reactions were studied using the succinyl derivative of either the acetal protected aminosugar or the azo dye. Target “naturalized” GADs were obtained after acid hydrolysis of the acetal protecting groups present on the sugar moiety.