X-ray diffraction and high-resolution NMR spectroscopy of methyl 3-azido-2,3-dideoxy-alpha-D-lyxo-hexopyranoside

The single-crystal X-ray diffraction and high-resolution 1H and 13C NMR spectral data for the title compound are reported. The influence of the ring oxygen atom on the J(1,2e) and J(4,5) coupling constants for 2-deoxy-D-lyxo- and -D-xylo-hexopyranosides is discussed.     

X-ray crystallographic and high-resolution NMR spectroscopy characterization of 4,6-di-O-acetyl-2,3-dideoxy-alpha-D-erythro-hex-2-enopyranosyl sulfamide

Single crystal X-ray diffraction and high-resolution ¹H and ¹³C NMR spectral data for 4,6-di-O-acetyl-2,3-dideoxy-α-d-erythro-hex-2-enopyranosyl sulfamide, a selective inhibitor of carbonic anhydrase isozyme IX, are reported. The ⁰H₅ was found to be the preferred form for this glycosyl sulfamide, both in the crystal lattice and in solution.     

Preparation, single-crystal X-ray diffraction and high-resolution NMR spectroscopic analyses of N-[(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-D,L-ribitol)-5-yl]trimethylammonium iodide

The synthesis and isolation of 1,4-anhydro-5-deoxy-5-iodo-2,3-O-isopropylidene-D,L-ribitol and N-[(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-D,L-ribitol)-5-yl]trimethylammonium iodide are described. The products were examined by (1)H, (13)C NMR spectroscopy, and N-[(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-D,L-ribitol)-5-yl]trimethylammonium iodide was additionally analyzed by X-ray crystallography.     

Synthesis, crystal structure, and high-resolution NMR spectroscopy of methyl 3-azido-2,3-dideoxy-4,6-di-O-p-tolylsulfonyl-alpha-D-xylo-hexopyranoside

Synthesis of methyl 3-azido-2,3-dideoxy-4,6-di-O-p-tolylsulfonyl- and -6-O-p-tolylsulfonyl-alpha-D-xylo-hexopyranosides is presented. High-resolution 1H and 13C NMR spectral data for both compounds and their precursors, and the single-crystal X-ray diffraction analysis for methyl 3-azido-2,3-dideoxy-4,6-di-O-p-tolylsulfonyl-alpha-D-xylo-hexopyranoside are reported. The influence of the O-protective group on the chemical shift of adjacent atoms in the 1H and 13C NMR spectra is discussed.     

Synthesis, the crystal structure, and high-resolution NMR spectroscopy of methyl 4-O-acetyl-3-azido-2,3,6-trideoxy-6-iodo-alpha-D-arabino-hexopyranoside

Selective tosylation followed by acetylation of methyl 3-azido-2,3-dideoxy-alpha-D-arabino-hexopyranoside (1) in pyridine at room temperature affords a mixture of methyl 4-O-acetyl-3-azido-2,3-dideoxy-6-di-O-p-tolylsulfonyl-alpha-D-arabino-hexopyranoside (4) and methyl 3-azido-2,3-dideoxy-4,6-di-O-p-tolylsulfonyl-alpha-D-arabino-hexopyranoside (3). Compound 4 undergoes nucleophilic displacement with sodium iodide in acetic anhydride to give methyl 4-O-acetyl-3-azido-2,3,6-trideoxy-6-iodo-alpha-D-arabino-hexopyranoside (7), whose crystal structure and (1H) and (13)C NMR data are reported. This compound adopts the 4C(1) conformation.     

Preparation and reactivity of a novel disaccharide, glucosyl 1,5-anhydro-D-fructose (1,5-anhydro-3-O-alpha-glucopyranosyl-D-fructose)

A novel disaccharide, glucosyl 1,5-anhydro-D-fructose (1,5-anhydro-3-O-alpha-glucopyranosyl-D-fructose, GAF) was enzymatically prepared from 1,5-anhydro-D-fructose (1,5-AF) and cyclomaltoheptaose (beta-cyclodextrin). Cyclodextrin glucanotransferase transferred various sizes of maltooligosaccharide to 1,5-AF. Glucoamylase digested the maltooligosyl chain of the products to a glucosyl residue giving a final product, GAF. An NMR analysis of GAF elucidated that the glucose residue was linked to C-3 of the 1,5-AF residue with an ether linkage. Reactivity on the aminocarbonyl reaction of GAF with bovine serum albumin was lower than that of 1,5-AF, but was higher than that of glucose.     

The thio-Mitsunobu reaction: a useful tool for the preparation of 2,5-anhydro-2-thio- and 3,5-anhydro-3-thiopentofuranosides

The unprotected methyl L-arabinofuranosides, D-ribofuranosides and D-xylofuranosides are transformed into the corresponding S-acetyl-5-thio derivatives by the thio-Mitsunobu reaction. Mesylation and subsequent reaction with sodium hydrogen carbonate led, depending on the configuration of the intermediate, to 2,5-anhydro-2-thio- or 3,5-anhydro-3-thiopentofuranosides. Due to inversion at C-3 or C-2 during the intramolecular nucleophilic displacement the products exhibit L-lyxo-, D-arabino- or D-lyxo-configuration. Analogously, the methyl 2,3-anhydro-D-ribofuranosides yielded 5-thio-S-acetates with intact 2,3-oxirane groups, which were cyclised with sodium hydrogen carbonate by epoxide ring opening and concomitant ring closure to form exclusively 3,5-anhydro-3-thio-D-xylofuranosides. A related 3,5-anhydro-3-seleno-D-lyxofuranoside was obtained by reaction of a 3,5-di-O-mesyl-D-arabinofuranoside with sodium hydrogen selenide. Several X-ray diffraction analyses proved the structures of the products.     

Conformations of methyl 2,5-di-O-acetyl-beta-D-glucofuranosidurono-6,3-lactone and 1,2,5-tri-O-acetyl-beta-D-glucofuranurono-6,3-lactone in the crystal structure and in solution

The single-crystal X-ray diffraction and high-resolution 1H and 13C NMR spectral data for methyl 2,5-di-O-acetyl-beta-D-glucofuranosidurono-6,3-lactone and 1,2,5-tri-O-acetyl-beta-D-glucofuranurono-6,3-lactone are reported. The lactones were synthesized as byproducts of reactions carried out to obtain methyl 1,2,3,4-tetra-O-acetyl-D-glucopyranuronate. The conformations of these lactones in the crystal structure and in solution are discussed. A 1T2-like conformation was found to be the preferred form for these lactones in both the crystal lattice and in solution.     

NMR studies of molybdate complexes of D-erythro-L-manno-octose and D-erythro-L-gluco-octose and their alditols

Different amounts and various types of bis-dinuclear tetradentate molybdate complexes of D-erythro-L-manno-octose, D-erythro-L-gluco-octose, D-erythro-L-manno-octitol and D-erythro-L-gluco-octitol were characterized by 1H and 13C NMR spectroscopy in aqueous solutions. Detailed analysis of 1H-(1)H coupling constants and NOEs, together with chemical shifts, allowed characterization of the different isomers of these complexes.     

Confirmation of the structure of tetra-O-(tert-butyldimethylsilyl)-D-glucono-1,4-lactone formed by silylation of D-glucono-1,5-lactone

The structure of tetra-O-(tert-butyldimethylsilyl)-D-glucono-1,4-lactone made by the silylation of D-glucono-1,5-lactone has been confirmed by single-crystal X-ray analysis.     

Synthesis of 2,5-anhydro-(beta-d-glucopyranosyluronate)- and (alpha-l-idopyranosyluronate)-d-mannitol hexa-O-sulfonate hepta sodium salt

Glycosidation of 2,5-anhydro-1,6-di-O-benzoyl-D-mannitol with methyl(2,3,4-tri-O-acetyl-alpha-d-glucopyranosyl-1-O-trichloroacetimidate)uronate in the presence of trimethylsilyl triflate afforded the corresponding 3-O-beta-glycoside, which after deprotection was converted into its hexa-O-sulfate with DMF x SO3 to give after treatment with sodium acetate and subsequent saponification of the methyl ester with sodium hydroxide the hepta sodium salt of 2,5-anhydro-3-O-(beta-d-glucopyranosyl uronate)-D-mannitol hexa-O-sulfate. Glycosidation of the same acceptor with the alpha-thiophenylglycoside of methyl 2,4-di-O-acetyl-3-O-benzyl-L-idopyranosyl uronate in the presence of NIS/TfOH afforded the corresponding 3-O-alpha-glycoside in very low yield, therefore the alpha-thiophenylglycoside of 2-O-acetyl-2,4-O-benzylidene-3-O-benzyl-L-idopyranose was used as donor. The terminal hydroxymethyl group of the obtained disaccharide was subsequently oxidised with NaOCl/TEMPO and the obtained iduronic acid derivative was converted into the hepta sodium salt of 2,5-anhydro-3-O-(-alpha-L-idopyranosyluronate)-D-mannitol hexa-O-sulfonate with DMF x SO3 and subsequent treatment with sodium acetate.     

Enzymatic synthesis of D-glucosone 6-phosphate (D-arabino-hexos-2-ulose 6-(dihydrogen phosphate)) and NMR analysis of its isomeric forms

D-Glucosone 6-phosphate (D-arabino-hexos-2-ulose 6-(dihydrogen phosphate)) was prepared from D-glucosone (D-arabino-hexos-2-ulose) by enzymatic conversion with hexokinase. The isomeric composition of D-glucosone 6-phosphate in aqueous solution was quantitatively determined by NMR spectroscopy and compared to D-glucosone. The main isomers are the alpha-anomer (58%) and the beta-anomer (28%) of the hydrated pyranose form, and the beta-D-fructofuranose form (14%).     

Crystal structures of D-tagatose 3-epimerase from Pseudomonas cichorii and its complexes with D-tagatose and D-fructose

Pseudomonas cichoriiid-tagatose 3-epimerase (P. cichoriid-TE) can efficiently catalyze the epimerization of not only d-tagatose to d-sorbose, but also d-fructose to d-psicose, and is used for the production of d-psicose from d-fructose. The crystal structures of P. cichoriid-TE alone and in complexes with d-tagatose and d-fructose were determined at resolutions of 1.79, 2.28, and 2.06 Å, respectively. A subunit of P. cichoriid-TE adopts a (β/α)₈ barrel structure, and a metal ion (Mn²⁺) found in the active site is coordinated by Glu152, Asp185, His211, and Glu246 at the end of the β-barrel. P. cichoriid-TE forms a stable dimer to give a favorable accessible surface for substrate binding on the front side of the dimer. The simulated omit map indicates that O2 and O3 of d-tagatose and/or d-fructose coordinate Mn²⁺, and that C3-O3 is located between carboxyl groups of Glu152 and Glu246, supporting the previously proposed mechanism of deprotonation/protonation at C3 by two Glu residues. Although the electron density is poor at the 4-, 5-, and 6-positions of the substrates, substrate-enzyme interactions can be deduced from the significant electron density at O6. The O6 possibly interacts with Cys66 via hydrogen bonding, whereas O4 and O5 in d-tagatose and O4 in d-fructose do not undergo hydrogen bonding to the enzyme and are in a hydrophobic environment created by Phe7, Trp15, Trp113, and Phe248. Due to the lack of specific interactions between the enzyme and its substrates at the 4- and 5-positions, P. cichoriid-TE loosely recognizes substrates in this region, allowing it to efficiently catalyze the epimerization of d-tagatose and d-fructose (C4 epimer of d-tagatose) as well. Furthermore, a C3-O3 proton-exchange mechanism for P. cichoriid-TE is suggested by X-ray structural analysis, providing a clear explanation for the regulation of the ionization state of Glu152 and Glu246.     

X-ray and conformational analysis of methyl 3-amino-2,3-dideoxy-alpha-D-arabino-hexopyranoside

The structure, conformation and configuration of methyl 3-amino-2,3-dideoxy-alpha-d-arabino-hexopyranoside were confirmed by (1)H NMR, (13)C NMR and IR spectroscopy, as well as by optical rotation. The structure of the compound studied was also determined by single crystal X-ray crystallography at 293 K and refined to a final R=0.0521 based on 1798 independent reflections. The title compound crystallized in the tetragonal space group P4(3) with a=6.572(1) angstrom, b=6.572(1) angstrom, c=41.161(8) angstrom, D(c)=1.324 Mgcm(-3) and V=1777.8(5) angstrom(3) for Z=8. The packing arrangement in the unit cell displayed a stratified structure. Moreover, medium-strength N-H. . .O and O-H. . .O hydrogen bonds, which stabilized the 3-D structure of compound I, were observed.     

Synthesis of 4-O-glycosylated 1,5-anhydro-d-fructose and of 1,5-anhydro-d-tagatose from a common intermediate 2,3-O-isopropylidene-d-fructose

Four novel disaccharides of glycosylated 1,5-anhydro-d-ketoses have been prepared: 1,5-anhydro-4-O-β-d-glucopyranosyl-d-fructose, 1,5-anhydro-4-O-β-d-galactopyranosyl-d-fructose, 1,5-anhydro-4-O-β-d-glucopyranosyl-d-tagatose, and 1,5-anhydro-4-O-β-d-galactopyranosyl-d-tagatose. The common intermediate, 1,5-anhydro-2,3-O-isopropylidene-β-d-fructopyranose, was prepared from d-fructose and was converted into the d-tagatose derivative by oxidation followed by stereoselective reduction to the 4-epimer. The anhydroketoses thus prepared were glycosylated and deprotected to give the disaccharides.     

Synthesis and intramolecular reactions of Tyr-Gly and Tyr-Gly-Gly related 6-O-glucopyranose esters

6-O-(L-Tyrosylglycyl)- and 6-O-(L-tyrosylglycylglycyl)-D-glucopyranose were synthesized by condensation of the pentachlorophenyl esters of the respective di- and tripeptide with fully unprotected D-glucose. The intramolecular reactivity of the sugar conjugates was studied in pyridine-acetic acid and in dry methanol, at various temperatures and for various incubation times. The composition of the incubation mixtures was monitored by a reversed-phase HPLC method that permits simultaneous analysis of the disappearance of the starting material and the appearance of rearrangement and degradation products. To determine the influence of esterification of the peptide carboxy group on its amino group reactivity, parallel experiments were done in which free peptides were, under identical reaction conditions, incubated with D-glucose (molar ratios 1:1 and 1:5). Depending on the starting compound, different types of Amadori products (cyclic and bicyclic form), methyl ester of peptides, and Tyr-Gly-diketopiperazine were obtained.     

Melting behaviour of D-sucrose, D-glucose and D-fructose

The melting behaviour of d-sucrose, d-glucose and d-fructose was studied. The melting peaks were determined with DSC and the start of decomposition was studied with TG at different rates of heating. In addition, melting points were determined with a melting point apparatus. The samples were identified as d-sucrose, alpha-d-glucopyranose and beta-d-fructopyranose by powder diffraction measurements. There were differences in melting between the different samples of the same sugar and the rate of heating had a remarkable effect on the melting behaviour. For example, T(o), DeltaH(f) and T(i) (initial temperature of decomposition) at a 1 degrees Cmin(-1) rate of heating were 184.5 degrees C, 126.6Jg(-1) and 171.3 degrees C for d-sucrose, 146.5 degrees C, 185.4Jg(-1) and 152.0 degrees C for d-glucose and 112.7 degrees C, 154.1Jg(-1) and 113.9 degrees C for d-fructose. The same parameters at 10 degrees Cmin(-1) rate of heating were 188.9 degrees C, 134.4Jg(-1) and 189.2 degrees C for d-sucrose, 155.2 degrees C, 194.3Jg(-1) and 170.3 degrees C for d-glucose and 125.7 degrees C, 176.7Jg(-1) and 136.8 degrees C d-fructose. At slow rates of heating, there were substantial differences between the different samples of the same sugar. The melting point determination is a sensitive method for the characterization of crystal quality but it cannot be used alone for the identification of sugar samples in all cases. Therefore, the melting point method should be validated for different sugars.     

Base catalysed isomerisation of aldoses of the arabino and lyxo series in the presence of aluminate

Base-catalysed isomerisation of aldoses of the arabino and lyxo series in aluminate solution has been investigated. L-Arabinose and D-galactose give L-erythro-2-pentulose (L-ribulose) and D-lyxo-2-hexulose (D-tagatose), respectively, in good yields, whereas lower reactivity is observed for 6-deoxy-D-galactose (D-fucose). From D-lyxose, D-mannose and 6-deoxy-L-mannose (L-rhamnose) are obtained mixtures of ketoses and C-2 epimeric aldoses. Small amounts of the 3-epimers of the ketoses were also formed. 6-Deoxy-L-arabino-2-hexulose (6-deoxy-L-fructose) and 6-deoxy-L-glucose (L-quinovose) were formed in low yields from 6-deoxy-L-mannose and isolated as their O-isopropylidene derivatives. Explanations of the differences in reactivity and course of the reaction have been suggested on the basis of steric effects.     

X-ray structure of the dipotassium salt of D-mannose 1-phosphate 3.25 hydrate

The first crystal structure of mannose 1-phosphate is described. The dipotassium hydrate salt crystallizes in the P2(1)2(1)2 space group. There are two independent dianions (I and II) in the asymmetric unit, which are alpha anomers adopting the 4C(1) chair conformation. The main difference between the two mannose 1-phosphate dianions is the orientation of the phosphate group with relation to the pyranosyl ring. In I, one of the phosphate oxygen atoms is antiperiplanar positions with respect to carbon atom C-1, whereas the two others are situated synclinally. The corresponding orientations of the terminal phosphate oxygen atoms in II are synperiplanar and anticlinal. The potassium cations are six- and seven-coordinate, mainly with O atoms of hydroxyl groups and water molecules. There are potassium channels extending along the c-axis. In the packing arrangement, water molecules and mannose phosphate groups also define two different types of layers parallel to a-axis. Within water channels there are extensive hydrogen-bonding networks.     

Synthesis and structure of selected quaternary N-(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-D,L-ribitol-5-yl)ammonium salts

The syntheses have been developed for quaternary N-(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-D,L-ribitol-5-yl)ammonium salts derived from five aromatic amines, pyridine, 2-methylpyridine, 3-carbamoylpyridine, 4-(N,N-dimethylamino)pyridine, and quinoline, as well as two tertiary aliphatic amines, trimethylamine and triethylamine. Reactions of 1,4-anhydro-2,3-O-isopropylidene-5-O-tosyl-D,L-ribitol with tri-n-propylamine and tri-n-butylamine were unsuccessful. The products were identified on the basis of their 1H and 13C NMR spectra. The structure of N-(1,4-anhydro-5-deoxy-2,3-O-isopropylidene-D,L-ribitol-5-yl)trimethylammonium tosylate was additionally elucidated by X-ray diffractometry.