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1.
Org Biomol Chem ; 19(33): 7190-7201, 2021 09 07.
Article in English | MEDLINE | ID: mdl-34382051

ABSTRACT

d-Allosamine is a rare sugar in Nature but its pyranoid form has been found α-linked in the core region of the lipopolysaccharide from the Gram-negative bacterium Porphyromonas gingivalis and in the chitanase inhibitor allosamidin, then ß-linked and N-acetylated. In water solution the monosaccharide N-acetyl-d-allosamine (d-AllNAc) shows a significant presence of four tautomers arising from pyranoid and furanoid ring forms and anomeric configurations. The furanoid ring forms both showed 3JH1,H2≈ 4.85 Hz and to differentiate the anomeric configurations a series of chemical shift anisotropy/dipole-dipole cross-correlated relaxation NMR experiments was performed in which the α-anomeric form showed notable different relaxation rates for its components of the H1 doublet, thereby making it possible to elucidate the anomeric configuration of each of the furanoses. The conformational preferences of the different forms of d-AllNAc were investigated by 3JHH, 2JCH and 3JCH coupling constants from NMR experiments, molecular dynamics simulations and density functional theory calculations. The pyranose form resides in the 4C1 conformation and the furanose ring form has the majority of its conformers located on the South-East region of the pseudorotation wheel, with a small population in the Northern hemisphere. The tautomeric equilibrium was quite sensitive to changes in temperature, where the ß-anomer of the pyranoid ring form decreased upon a temperature increase while the other forms increased.

2.
Clin Vaccine Immunol ; 19(11): 1889-93, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22993407

ABSTRACT

Immunostimulatory properties of synthetic structures mimicking the ß-(1→2)-linked mannans of Candida albicans were evaluated in vitro. Contrary to earlier observations, tumor necrosis factor (TNF) production was not detected after stimulation with mannotetraose in mouse macrophages. Divalent disaccharide 1,4-bis(α-D-mannopyranosyloxy)butane induced TNF and some molecules induced low levels of gamma interferon (IFN-γ) in human peripheral blood mononuclear cells (PBMC).


Subject(s)
Candida albicans/chemistry , Candida albicans/immunology , Mannans/chemical synthesis , Mannans/immunology , Animals , Cells, Cultured , Humans , Interferon-gamma/metabolism , Leukocytes, Mononuclear/immunology , Macrophages/immunology , Mice , Mice, Inbred BALB C , Tumor Necrosis Factor-alpha/metabolism
3.
Carbohydr Res ; 346(11): 1311-9, 2011 Aug 16.
Article in English | MEDLINE | ID: mdl-21621752

ABSTRACT

The computer program casper uses (1)H and (13)C NMR chemical shift data of mono- to trisaccharides for the prediction of chemical shifts of oligo- and polysaccharides. In order to improve the quality of these predictions the (1)H and (13)C, as well as (31)P when applicable, NMR chemical shifts of 30 mono-, di-, and trisaccharides were assigned. The reducing sugars gave two distinct sets of NMR resonances due to the α- and ß-anomeric forms. In total 35 (1)H and (13)C NMR chemical shift data sets were obtained from the oligosaccharides. One- and two-dimensional NMR experiments were used for the chemical shift assignments and special techniques were employed in some cases such as 2D (1)H,(13)C-HSQC Hadamard Transform methodology which was acquired approximately 45 times faster than a regular t(1) incremented (1)H,(13)C-HSQC experiment and a 1D (1)H,(1)H-CSSF-TOCSY experiment which was able to distinguish spin-systems in which the target protons were only 3.3Hz apart. The (1)H NMR chemical shifts were subsequently refined using total line-shape analysis with the PERCH NMR software. The acquired NMR data were then utilized in the casper program (http://www.casper.organ.su.se/casper/) for NMR chemical shift predictions of the O-antigen polysaccharides from Klebsiella O5, Shigella flexneri serotype X, and Salmonella arizonae O62. The data were compared to experimental data of the polysaccharides from the two former strains and the lipopolysaccharide of the latter strain showing excellent agreement between predicted and experimental (1)H and (13)C NMR chemical shifts.


Subject(s)
Magnetic Resonance Spectroscopy/methods , Monosaccharides/chemistry , Oligosaccharides/chemistry , Polysaccharides/chemistry , Trisaccharides/chemistry , Lipopolysaccharides/chemistry
4.
Carbohydr Res ; 345(8): 984-93, 2010 May 27.
Article in English | MEDLINE | ID: mdl-20347069

ABSTRACT

The synthesis of two novel carbasugar analogues of alpha-L-iduronic acid is described in which the ring-oxygen is replaced by a methylene group. In analogy with the conformational equilibrium described for alpha-L-IdopA, the conformation of the carbasugars was investigated by (1)H and (13)C NMR spectroscopy. Hadamard transform NMR experiments were utilised for rapid acquisition of (1)H,(13)C-HSQC spectra and efficient measurements of heteronuclear long-range coupling constants. Analysis of (1)H NMR chemical shifts and J(H,H) coupling constants extracted by a total-lineshape fitting procedure in conjunction with J(H,C) coupling constants obtained by three different 2D NMR experiments, viz., (1)H,(13)C-HSQC-HECADE, J-HMBC and IPAP-HSQC-TOCSY-HT, as well as effective proton-proton distances from 1D (1)H,(1)H T-ROE and NOE experiments showed that the conformational equilibrium [formula in text] is shifted towards (4)C(1) as the predominant or exclusive conformation. These carbasugar bioisosteres of alpha-l-iduronic acid do not as monomers show the inherent flexibility that is anticipated to be necessary for biological activity.


Subject(s)
Glycosides/chemistry , Glycosides/chemical synthesis , Iduronic Acid/analogs & derivatives , Magnetic Resonance Spectroscopy , Molecular Conformation , Molecular Structure
5.
J Am Chem Soc ; 130(27): 8769-72, 2008 Jul 09.
Article in English | MEDLINE | ID: mdl-18543925

ABSTRACT

The migration of acetyl, pivaloyl, and benzoyl protective groups and their relative stabilities at variable pH for a series of beta- d-galactopyranoses were studied by NMR spectroscopy. The clockwise and counterclockwise migration rates for the different ester groups were accurately determined by use of a kinetic model. The results presented provide new insights into the acid and base stabilities of commonly used ester protecting groups and the phenomenon of acyl group migration and may prove useful in the planning of synthesis strategies.


Subject(s)
Galactose/chemistry , Glucosides/chemistry , Hydrogen-Ion Concentration , Kinetics , Magnetic Resonance Spectroscopy , Molecular Conformation
6.
Carbohydr Res ; 343(1): 101-12, 2008 Jan 14.
Article in English | MEDLINE | ID: mdl-17980865

ABSTRACT

Complete assignment of the (1)H and (13)C NMR spectra of all possible d-glucopyranosyl-d-glucopyranosides was performed and the (1)H chemical shifts and proton-proton coupling constants were refined by computational spectral analyses (using PERCH NMR software) until full agreement between the calculated and experimental spectra was achieved. To support the experimental results, the (1)H and (13)C chemical shifts and the spin-spin coupling constants between the non-hydroxyl protons of alpha- and beta-d-glucopyranose (1a and 1b) were calculated with density functional theory (DFT) methods at the B3LYP/pcJ-2//B3LYP/6-31G(d,p) level of theory. The effects of different glycosidic linkage types and positions on the glucose ring conformations and on the alpha/beta-ratio of the reducing end hydroxyl groups were investigated. Conformational analyses were also performed for anomerically pure forms of methyl d-glucopyranosides (13a and 13b) and fully protected derivatives such as 1,2,3,4,6-penta-O-acetyl-d-glucopyranoses (14a and 14b).


Subject(s)
Glycosides/chemistry , Nuclear Magnetic Resonance, Biomolecular/methods , Carbohydrate Conformation , Carbon Isotopes , Models, Molecular
7.
Org Biomol Chem ; 3(16): 2924-9, 2005 Aug 21.
Article in English | MEDLINE | ID: mdl-16186923

ABSTRACT

Four derivatives of 2,6-diaminopurine (1) were synthesised and characterised. When 1 was reacted with chloroacetaldehyde, 5-aminoimidazo[2,1-i]purine (2), 9-aminoimidazo[2,1-b]purine (3), 9-aminoimidazo[1,2-a]purine (4) and diimidazo[2,1-b:2',1'-i]purine (5) were formed. The purified products (3-5) were fully characterised by MS, complete NMR assignments as well as fluorescence and UV spectroscopy. The purified, isolated yields of these products (3-5) varied from 2.5 to 30%. The relative stability of different tautomers was investigated by theoretical calculations. Fluorescence characteristics are also discussed and compared to the starting material 1 and a reference molecule 2-aminopurine.


Subject(s)
DNA Adducts/chemical synthesis , 2-Aminopurine/analogs & derivatives , 2-Aminopurine/chemical synthesis , 2-Aminopurine/chemistry , DNA Adducts/chemistry , Fluorescence , Magnetic Resonance Spectroscopy , Models, Molecular
8.
Org Lett ; 6(16): 2673-6, 2004 Aug 05.
Article in English | MEDLINE | ID: mdl-15281741

ABSTRACT

The major of two solution-state tautomers observed for an etheno product of 2,6-diaminopurine was identified as the tautomer H-1 on the basis of the recognition of the two-bond coupling between the NH proton and C-9a and the three-bond coupling between the NH proton and C-3a. The couplings were distinguished as being over two- or three bonds by determination of the sign of the coupling using two-dimensional heteronuclear NMR, negative in the former case and positive in the latter case. [structure: see text]

9.
Org Biomol Chem ; 2(6): 821-7, 2004 Mar 21.
Article in English | MEDLINE | ID: mdl-15007409

ABSTRACT

Four novel derivatives of 2-amino-9-(beta-D-ribofuranosyl)purine (1) were synthesised and fully characterised. When 1 was reacted with chloroacetaldehyde (a), 2-chloropropanal (b), bromomalonaldehyde (c) and a mixture of chloroacetaldehyde + malonaldehyde (d), 3-(beta-D-ribofuranosyl)-imidazo-[1,2a]purine (2), 3-(beta-D-ribofuranosyl)-5-methylimidazo-[1,2a]purine (3), 3-(beta-D-ribofuranosyl)-5-formylimidazo-[1,2a]purine (4) and 9-(beta-D-ribofuranosyl)-2-(3,5-diformyl-4-methyl-1,4-dihydro-1-pyridyl)purine (5) were formed, respectively. The products were isolated, purified by chromatography and characterised by MS, complete NMR assignment as well as fluorescence and UV spectroscopy. The yields of these reactions were moderate (14-20%). The fluorescence properties differed from those of the starting compound and the quantum yields were considerably lower.


Subject(s)
Nucleosides/chemistry , Nucleosides/chemical synthesis , Drug Stability , Hydrogen-Ion Concentration , Molecular Structure , Nucleosides/pharmacology , Spectrum Analysis
10.
J Org Chem ; 69(1): 18-25, 2004 Jan 09.
Article in English | MEDLINE | ID: mdl-14703374

ABSTRACT

The solution-state conformations of various galactose derivatives were determined by comparison of the experimental (1)H-(1)H vicinal coupling constants to those calculated using density functional theory (DFT) at the B3LYP/cc-pVTZ//B3LYP/6-31G(d,p) level of theory. The agreement between the experimental and calculated vicinal coupling constants for 1,2:3,4-di-O-isopropylidene-alpha-d-galactopyranose was good, thereby confirming an (O)S(2) skew conformation for it and its derivatives on the basis of their similar observed couplings. Single-crystal X-ray analysis of 1,2:3,4-di-O-isopropylidene-6-O-(3,4,6-tri-O-acetyl-2-deoxy-2-N-phthalimido-beta-d-glucopyranosyl)-alpha-d-galactopyranose and 1,2,3,4,6-penta-O-acetyl-alpha-d-galactopyranose provided (O)S(2) and (4)C(1) conformations, respectively, for the galactose ring in the solid state. The solid-state structures proved to be suitable starting structures for further DFT structure refinement or for immediate calculation of the coupling constants.


Subject(s)
Galactose/chemistry , Crystallization , Crystallography, X-Ray , Magnetic Resonance Spectroscopy , Models, Molecular , Protons , Solutions
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