Janusz Madaj

Solvent‐Free Thermal Dehydration of Pentitols on Zeolites

Abstract Dehydration of D‐arabinitol, ribitol, and xylitol at high temperature in the presence of molecular sieves without solvent in an argon atmosphere is described. Products arising after the dehydration–cyclization (cyclodehydration) reaction with retention or inversion of the configuration of asymmetric carbon atoms, were observed. Complete analytical separations of exhaustively O‐acetylated reaction products were achieved by means of GC. The chemical structures of the compounds obtained were assigned using co‐injection with standards. #Dedicated to Professor Gérard Descotes on the occasion of the jubilee of his scientific career.

Structure and properties of the exopolysaccharides produced by Pseudomonas mutabilis T6 and P. mutabilis ATCC 31014.

This paper presents a study on the purification, primary structure, and rheological properties of exopolysaccharides isolated from cultures of Pseudomonas mutabilis T6 and P. mutabilis ATCC 31014. Both polymers are exopolysaccharides of D-mannose. The mannan isolated from P. mutabilis T6 contains on average about 5% of residual β-D-glucose, in contrast to the mannan from P. mutabilis ATCC 31014, which contained only trace amounts of residual β-D-glucose (less than 1%). Based on the (13)C NMR spectra, all of the remaining carbohydrates in the exopolysaccharides occur in the form of pyranose rings. All of the mannose residues have the α configuration at the anomeric carbon atom while the glucose adopts the β configuration. The reaction of both polysaccharide hydrolysates with an optically active alcohol indicates that all of the sugar residues have the D configuration. We found that the main chain of the exopolysaccharide is composed of mannose residues connected through α-(1→6) linkages, of which a large number are substituted on O2 with D-mannose and the remaining are substituted with di- to pentasaccharide fragments. The rheological properties of the exopolysaccharide isolated from P. mutabilis T6 show that its viscosity is over 30 times greater than that of P. mutabilis ATCC 31014.

Cyclization of N(Tetra-O-acetyl-d-gluco- and d-Mannopyranosyl)-Pyridinium Salts in a Methanolic Solution of Sodium Methylate

Abstract N-(2,3,4,6-Tetra-O-acetyl-α-d-gluco-, β-d-gluco- and β-d-mannopyranosyl)-pyridinium salts were obtained and their structures were determined by 2D 1H NMR spectroscopy. The compounds obtained were treated with a methanolic solution of sodium methylate. The β-anomer of the d-gluco derivative cyclizes via Brigls anhydride but the α anomer is competitively transformed according to the SN2 and SN1 mechanisms. The β-d-manno derivative does not cyclize under the conditions used. Comparison of the qualitative and quantitative results of the reaction studied enabled estimation of the influence of configuration at C-1 and C-2 on the course of cyclization. All product mixtures were separated by capillary gas chromatography (CGC) as exhaustively O-acetylated derivatives and their components were identified by coinjection with authentic materials.

Side products of glycosidation with selected 2-acetamido-2-deoxy-D-glucopyranosides

Allyl 2-acetamido-4,6-O-benzylidene-2-deoxy-3-O-formyl-alpha-D-glucopyranoside, N-acetyl-2,3,4-tri-O-acetyl-L-fucopyranosylamine and products of O-acetyl group migration were found as side products during glycosidation of selected 2-acetamido-2-deoxy-D-glucopyranosides.

X-Ray diffraction and high resolution NMR analysis of methyl d-glucopyranuronate derivatives

X-Ray diffraction and high resolution 1H and 13C NMR spectral data for methyl 2,3,4,-tri-O-acetyl-alpha-D-glucopyranuronate and methyl (allyl 2,3,4-tri-O-acetyl- beta-D-glucopyranosid)uronate are presented. Both compounds adopt the 4C1 conformation.

Zinc-N-base mediated synthesis of pyranoid glycals mechanistic studies

Abstract Reactions of acetobromoglucose 1 or acetylated 1-bromo-D-galactopyranosyl cyanide 3 with zinc dust in the presence of a N-base (1-methylimidazole, 4-methylpyridine, or triethylamine, pyridine, respectively) in ethyl acetate or benzene were efficiently inhibited by 10–30 mol % of 1,4-dinitrobenzene, elemental sulfur, or carbon tetrachloride. Presence of glycosyl radicals in these reactions was also shown by trapping them with tert-dodecyl mercaptan or methyl acrylate. Based on these observations and the high yielding formation of glycal derivatives 2 and 4 of high purity a free radical chain mechanism is proposed for the transformations.

1,6-Cyclization Reactions of Selected Aldohexopyranoses via Their 1-O-Tosyl Derivatives

Abstract 2,3,4,6-Tetra-O-acetyl-d-gluco-, d-galacto- and d-mannopyranoses were tosylated with p-tolenesulfonyl chloride to afford their 1-O-tosyl derivatives which were cyclized “in situ” in a methanolic solution of sodium methoxide. 1,6-Cyclization products were obtained only with d-glucose and d-galactose derivatives. Cyclization of derivatives of d-glucose i.e. 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl chloride, 3,4,6-tri-O-acetyl-1,2-anhydro-α-d-glucopyranose (Brigls anhydride) and 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide enabled the estimation of the influence of configuration at C-1 and C-2 on the course of cyclization. All product mixtures were separated by capillary gas chromatography (CGC) and their components were identified by coinjection with standards.

Capillary gas chromatographic separations of a multi-component mixture of polyalcohol compounds

Capillary gas chromatographic separation conditions were established for a 31-component mixture of polyhydroxy compounds containing two tetritols, three pentitols, six hexitols, seven monoanhydropentitols, eight monoanhydrohexitols, three dianhydrohexitols, pentaerythritol and myoinositol. Mixtures of per-O-acetyl or per-O-trimethylsilyl derivatives of these compounds were separated on fused-silica columns using highly polar DB-23 and non-polar HP-5 stationary phases, respectively. Relative retention times for each compound with respect to pentaerythritol and myoinositol and methylene units were determined.

Molecular modeling of Gram-positive bacteria peptidoglycan layer, selected glycopeptide antibiotics and vancomycin derivatives modified with sugar moieties.

Proper understanding of the mechanisms of binding to Gram-positive bacteria cell wall layers-especially to the peptidoglycan (PG) layer, seems to be crucial for proper development of new drug candidates which are effective against these bacteria. In this work we have constructed two different models of the Gram-positive bacteria PG layer: the layered and the scaffold models. PG conformational changes during geometry optimization, models relaxation, and molecular dynamics were described and discussed. We have found that the border surface of both PG layer models differs from the surface located away from the edge of models and the chains formed by disaccharide units prefer helix-like conformation. This curling of PG chains significantly affects the shape of antibiotic-accessible surface and the process is thus crucial for new drug development. Glycopeptide antibiotics effective against Gram-positive bacteria, such as vancomycin and its semisynthetic derivatives-oritavancin and telavancin, bind to d-alanyl-d-alanine stem termini on the peptidoglycan precursors of the cell wall. This binding inhibits cross-linking between the peptides and subsequently prevents cell wall synthesis. In this study some of the aspects of conformational freedom of vancomycin and restrictions from the modifications of vancomycin structure introduced into oritavancin and telavancin and five other vancomycin derivatives (with addition of 2-acetamido-2-deoxy-β-d-galactopyranosylamine, 2-acetamido-2-deoxy-β-d-glucopyranosylamine, 1-amine-1-deoxy-d-glucitol, 2-amino-2-deoxy-d-galactitol, or 2-amino-2-deoxy-d-glucitol to the C-terminal amino acid group in the vancomycin) are presented and discussed. The resulting molecular dynamics trajectories, root mean square deviation changes of aglycon and saccharide moieties as well as a comparative study of possible interactions with cyclic and chain forms of modified groups have been carried out, measured, and analyzed. Energetically advantageous conformations show close similarity to the structures known from the experimental data, but the diversity of others suggest very high conformational freedom of all modeled antibiotics and vancomycin derivatives. Alditol derivatives move closer to the peptidoglycan chain more easily but they also form intramolecular interactions more frequently than their homologous cyclic forms. One of the proposed derivatives seems to be a promising agent which is efficient in treatment of infections caused by Gram-positive bacteria.

X-ray diffraction and high resolution NMR spectroscopy analysis of methyl β--glucofuranosidurono-6,3-lactone

Abstract The X-ray diffraction and high resolution 1 H- and 13 C NMR spectral data are reported for the title compound.