Francisca Cabrera-Escribano

Synthesis of 4-(4,6-di-O-benzyl-2,3-dideoxy-β-d-erythro-hex-2-enopyranosyl)pyrazoles from 3,4,6-tri-O-acetyl-d-glucal

Abstract 3-(4,6-Di- O -benzyl-2,3-dideoxy- β - d - erythro -hex-2-enopyranosyl)-2,4-pentanedione and its analogue 2-(4,6-di- O -benzyl-2,3-dideoxy- β - d - erythro -hex-2-enopyranosyl)-1-phenyl-1,3-butanedione, prepared from 3,4,6-tri- O -acetyl-1,5-anhydro-2-deoxy- d - arabino -hex-1-enitol (3,4,6-tri- O -acetyl- d -glucal), reacted with hydrazine and its methyl-, phenyl-, p -tolyl, and p -methoxyphenyl- derivatives in ethanol, at room temperature, to afford, in 71–96% yields, a series of 4-(4,6-di- O -benzyl-2,3-dideoxy- β - d - erythro -hex-2-enopyranosyl)-3-methylpyrazoles having the N-1 free or substituted by the foregoing groups, and the C-5 substituted by a methyl or phenyl group. The reactions of the 1-phenyl-1,3-butanedione derivative were highly regioselective. Catalytic hydrogenation of some of these novel compounds gave the respective 4′,6′-di- O -deprotected-2′,3′-saturated compounds in 51–67% yields. The acetolysis/methanolysis of one of the title compounds led to the formation of the 4′,6′-di- O -debenzylated 2′,3′-unsaturated pyrazole C -nucleoside in poor yield.

Novel rearrangement reactions in the fluorination of methyl 3-C-methyl-3-nitro-α-l-hexopyranosides by the DAST reagent

Abstract A simple method for the preparation of 1-fluoro- and/or 5-fluoro-3-branched-chain sugar derivatives by reaction of DAST with methyl 3- C -methyl-3-nitro-α- l -hexopyranosides is described. The reaction involves rearrangement with or without ring contraction, depending on the 1,2 relative configuration and the presence of a free OH group at C-4 in the substrate. A new, useful aldehydo -sugar ramified at C-3 is easily accessible in good yield by the route reported here.

Rearrangement reactions in the fluorination of 3-deoxy-3-C-methyl-3-nitro-hexopyranosides (and hexo-1-thiopyranosides) of the d- and l-series by the DAST reagent

Abstract Fluorination of diverse 3-deoxy-3- C -methyl-3-nitro-hexopyranosides and hexo-1-thiopyranosides of the d - and l -series by the DAST reagent was studied in order to establish, on this 3-branched-chain sugar domain, the influence of the stereochemical relationship of the substituents at positions 1 and 2, as well as the protection of the HO-4, on the kinds of rearrangement reaction promoted by this fluorinating agent. Three classes of pyranosidic substrate were employed: ( a ) 1,2- trans configured, irrespective of whether HO-4 is protected or not; ( b ) 4- O -protected 1,2- cis configured; and ( c ) 4- O -unprotected 1,2- cis configured. They were prepared starting from simple glycosides through routes involving a Baer reaction and subsequent transformations by known methodology. All the substrates of class a essayed underwent, on treatment with DAST at room or higher temperatures, a rearrangement involving a 1,2-shift to give both the anomeric 2-inverted pyranosyl fluorides (or, for the 1-thioglycosides, only the α fluoride). Substrates of class b led, through a mechanism similar to that proposed for transformations of related substrates, to ring-contracted 2,5-anhydro-1-fluoro-1- O -methyl- (or 1-deoxy-1-phenylthio-)hexitol derivatives (sometimes as 1-epimers), which are precursors of 2,5-anhydro- aldehydo -sugars. Substrates of class c led to 4,5-anhydro-1-fluoro-1- O -methylalditol derivatives in all cases, together with a ring-contracted 5-fluoro-hexofuranoside in only one case; a rationalisation for their formation is proposed.

Branched-chain fluoro nitro d- and l-sugars from glucose

Abstract Mixed crystals of methyl 3-deoxy-3- C -methyl-3-nitro-α- d - and β- l -glucopyranosides (1:1), easily available from d -glucose by means of the Baer reaction, were completely characterised by X-ray diffraction analysis. These diastereomeric components, separation of which could be achieved through their 4,6- O -benzylidene derivatives, were selectively fluorinated at position 6 by treatment with DAST and stereoselectively transformed into phenyl 3-deoxy-3- C -methyl-3-nitro-1-thio-β- d -glucopyranoside and phenyl 3-deoxy-3- C -methyl-3-nitro-1-thio-β- l -glucopyranoside, respectively. Fluorination with DAST of each pure enantiomer afforded, depending on the conditions, the corresponding enantiomeric phenyl 3,6-dideoxy-6-fluoro-3- C -methyl-3-nitro-1-thio-β- d - and β- l -glucopyranosides or the respective rearranged 2,3,6-trideoxy-6-fluoro-3- C -methyl-3-nitro-2-phenylthio-α- d - and α- l -mannopyranosyl fluorides. This route constitutes a simple method for obtaining fair-to-good yields of 6-fluorinated branched-chain d - and l -sugar derivatives, potentially useful as glycosyl donors, starting from d -glucose.

Use of gold nanoparticles as crosslink agent to form chitosan nanocapsules: study of the direct interaction in aqueous solutions.

A systematic study of the interaction between free anionic gold nanoparticles and chitosan in a solution is presented. A spectroscopic study of the interaction between 10nm gold nanoparticles and low molecular weight chitosan is reported as a function of the concentration and pH of the polymer in a solution. Zeta potential measurements and TEM images indicate the effective aggregation of the nanoparticles in the presence of chitosan. At the same time, anionic gold nanoparticles act as crosslink agents to form chitosan nanocapsules with an average molecular size of 260nm. The changes of the surface plasmon band due to the adsorption of the polymer on the nanoparticle surface allow using of the citrate gold nanoparticles as sensors of the polymer for analytical purposes. The limit of detection for chitosan biopolymer is 69nM. The optimum pH for the interaction between the biopolymer and the nanoparticles is found at a value of 6.4, obtained from spectrophotometric measurements and applying a deconvolution analysis of the experimental data. A simple model based on molecular surface electrostatic interactions is proposed to understand the pH dependence of the investigated system.

Higher glycosamino acid precursors: C7 and C8 aminodialdoses via regio- and stereoselective [3+2] cycloaddition of vinyl trimethylsilane to C-glycosyl nitrones

Abstract Protected C 7 and C 8 aminodialdoses were prepared stereoselectively from readily available C 5 and C 6 monosaccharide N -benzyl nitrones, by regio- and diastereoselective 1,3-dipolar cycloaddition reactions with vinyl trimethylsilane, followed by acetyl chloride-mediated cleavage of the 5-(trimethylsilyl)isoxazolidine formed. The cycloaddition reaction took place in moderate to good global yields (67–74%); estimation of diastereoselectivities from isolated yields showed total endo preference for the reaction of the d - galacto configured nitrone and high endo preference for the d - ribo analogue, but exo preference for the d - xylo configured substrate. Attack on the re face of the nitrone was predominant in all cases. The absolute configuration of one of the protected 3-(α- d - galacto -pentopyranos-5-yl)isoxazolidine products was assigned by X-ray crystallographic analysis, allowing correlation of the configuration at the new stereogenic centre in the corresponding aminodialdose. For non-crystalline isoxazolidines, configurations were assigned on the basis of NOESY experiments and/or chemical correlation. Combined yields of aminodialdoses coming from isoxazolidines having identical configuration at C(3) sometimes reached high values (up to 90%). These compounds are precursors of higher-chain glycosamino acids.

1,3-Dicarbonyl sugar derivatives from sugar nitro-olefins

Abstract The sugar nitro-olefins 5–9 , easily available from the aldehydo -sugars 1–4 and simple nitroalkanes, undergo a slow transformation, by treatment in DMF with a mixture of tetrabutylammonium hydrogensulfate (2 mol) and potassium fluoride (4 mol) at room temperature, to give the corresponding enol ethers 10–14 , in 10–71% yields, as E / Z mixtures, with the exception of 12 , which is configurationally homogeneous. The spectroscopic properties of the enol ethers 10–14 are in agreement with their structures. A proof of the potential usefulness of these compounds as equivalent of sugar 1,3-dicarbonyl compounds is the reaction of 12 with hydrazine hydrate, which affords the pyrazole derivative 15 (53%). The formation of 10–14 from 5–9 may be rationalised in terms of a vinylogous Nef-type reaction. Jacobson conditions, as applied to the nitroalkene 7 , led to the dimethyl acetal 16 (47%) as a E / Z mixture, which was transformed into the pyrazole derivative 15 in poor yield (14%). This method is therefore less convenient for 7 than the one described here, which seems to be of wider applicability in the carbohydrate field.

Synthesis of hyperpolarizable biomaterials at molecular level based on pyridinium–chitosan complexes

Potential NLO-phore materials based on chitosan are described for the first time in this study. A series of fluorescent and quaternized pyridinium–chitosan derivatives have been synthesized by reaction of this polymer with easily available tunable pyrylium tetrafluoroborate salts. Among other spectroscopic techniques, 19F NMR, 13C CPMAS NMR and 2D diffusion experiments, were used to confirm the structures of the new pyridinium–chitosan complexes that show high fluorescence intensity. Degrees of N-substitution were achieved lower than 4.3%, allowing the original physicochemical properties of the biopolymer to be preserved. DFT calculations have been performed to investigate the molecular features related to the NLO properties in these compounds. NLO behavior was found to be clearly dependent on the nature and location of the substituent into the pyridinium core. Theoretical data reveal a large permanent dipolar moment, polarizabilities and hyperpolarizabilities making these molecules promising candidates as supramolecular devices exhibiting NLO properties with potentially enhanced solvatochromic properties.

Towards cyclic, conformationally constrained, fluorine-containing β-amino acid derivatives from d-glucose

Abstract Novel, potentially bioactive, fluorinated branched-chain monosaccharides were obtained by reaction of diethylaminosulphur trifluoride (DAST) with a series of methyl 3- C -cyano-3-ethoxycarbonyl-β- d -glucopyranoside derivatives, including the 4,6- O -benzylidene derivative and their 3- C -( N -protected aminomethyl) reduction products, as well as the phenyl 3- C -cyano-3-ethoxycarbonyl-1-thio-α- d -(and β- d -)glucopyranosides. The absolute configuration at C(3) was unambiguously assigned for all compounds on the basis of X-ray crystallographic analysis of methyl 4,6- O -benzylidene-3- C -cyano-3-deoxy-3-ethoxycarbonyl-β- d -glucopyranoside, corroborating the previous tentative assignment by other authors for the 4,6-unprotected compound. The course of the fluorination depended on the reaction temperature and the substitution pattern of the substrate. Thus, for methyl 3- C -cyano-3-ethoxycarbonyl-β- d -glucopyranoside, fluorination occurred exclusively at C(6), but for the phenylthio analogue, a 2-deoxy-2-phenylthio-α- d - manno -configured glycosyl fluoride and its 6-fluoro derivative were obtained, resulting from the expected rearrangement reaction, whilst starting from the phenylthio α anomer, only the unrearranged 6-fluoro compound was formed. Rearrangement was also observed in the fluorination of methyl 4,6- O -benzylidene-3- C -( N -protected aminomethyl)-β- d -glucopyranoside, which led to the 2- O -methyl-α- d -mannopyranosyl fluoride derivative as the sole product. This methodology may constitute a simple route to enantiopure conformationally constrained cyclic fluorinated β-amino acids having the α carbon atom shared with a pyranose ring, although only moderate yields were achieved, particularly in the fluorination step.

Fluorescent imino and secondary amino chitosans as potential sensing biomaterials.

A variety of fluorescent imino and secondary amino chitosans were synthesized under very mild conditions by reaction of the biopolymer amino functions with aromatic aldehydes in an acidified methanolic suspension. Simultaneous reactions of several aldehydes with chitosan were successfully carried out, and kinetic studies showed that 1-pyrenecarboxaldehyde reacts the fastest among them. An unprecedented study on the evaluation of the degree of N-substitution (DS, ranging from 31.7% to 12.0%) for the chitosan Schiff bases by using solid state CPMAS (13)C NMR is performed. A linear correlation between the DS obtained for the secondary amino chitosans by (1)H NMR (55.3-10.2%) and those obtained by CPMAS (13)C NMR (34.4-13.8%) has allowed us to calculate an empirical correlation factor that could be applied on chitosan-based aromatic systems. The new chiral-labelled chitosan derivatives exhibit a stable fluorescent behaviour, which was used to explore solvent sensoring applications.