Andrzej Nowacki

Fully acetylated 1,5-anhydro-2-deoxypent-1-enitols and 1,5-anhydro-2,6-dideoxyhex-1-enitols in DFT level theory conformational studies

Geometry optimizations at the B3LYP level of density functional theory (DFT) are reported for the (4)H(5) and (5)H(4) conformations of four glycals: 3,4-di-O-acetyl-1,5-anhydro-2-deoxy-D-erythro-pent-1-enitol (3,4-di-O-acetyl-D-arabinal), its D-threo isomer (3,4-di-O-acetyl-D-xylal), 3,4-di-O-acetyl-1,5-anhydro-2,6-dideoxy-D-arabino-hex-1-enitol (3,4-di-O-acetyl-D-rhamnal), and its D-lyxo isomer (3,4-di-O-acetyl-D-fucal). The Gibbs free energies, relative Gibbs free energies and geometry parameters are presented for all the optimized structures. Conformational analysis of both the acetoxy groups and 1,2-unsaturated pyranoid ring is performed. It is demonstrated that the acetoxy group is planar and adopts two conformations with regard to the Ac-O bond rotations, one of which is strongly preferred. One of the hydrogen atoms of the methyl group is always oriented synperiplanarly whereas the remaining two anticlinally with respect to the carbonyl oxygen. With regard to the AcO-R bond rotations some of the orientations are forbidden. The calculations indicate that 3,4-di-O-acetyl-D-arabinal adopts mainly the (4)H(5) conformation, whereas 3,4-di-O-acetyl-D-xylal prefers the (5)H(4) form, owing to the vinylogous anomeric effect (VAE). Competition between the VAE and quasi 1,3-diaxial interactions means that both 3,4-di-O-acetyl-D-rhamnal and 3,4-di-O-acetyl-D-fucal remain in the (4)H(5)⇄(5)H(4) conformational equilibrium, shifted in the (4)H(5) direction. It seems that the orientation of the 4-OAc group influences the quasi 1,3-diaxial interactions between 3-OAc and 5-CH(3) groups. Theoretical results are compared with assignments based on (1)H NMR studies.

Methyl 3-amino-2,3,6,-trideoxy-L-hexopyranosides in DFT level theory conformational studies.

Geometry optimizations at the B3LYP level of density functional theory are reported for the (1)C4 and (4)C1 conformations of four theoretically possible alpha and beta methyl 3-amino-2,3,6-trideoxy-L-hexopyranosides. The Gibbs free energies, relative Gibbs free energies, and geometry parameters are presented for all the optimized structures. Conformational analysis of the pyranose ring is performed for each stereoisomer on the basis of calculated rotamer populations. It is demonstrated that the alpha/beta-L-arabino, alpha/beta-L-lyxo, and alpha-L-ribo stereoisomers adopt the (1)C4 conformation, whereas beta-L-ribo and alpha/beta-L-xylo stereoisomers remain in (1)C4 <==> (4)C1 conformational equilibrium. The preference of the alpha over the beta anomers is due to the endo-anomeric effect. The factors affecting the stability of pyranose ring conformations are discussed, as is the influence of hydrogen bonds on the orientation of the hydroxyl and amino groups. Figures of the most stable conformers are presented.

N-Alkyl derivatives of diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside; synthesis and antimicrobial activity

Summary Diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside is a synthetic saponin exhibiting attractive pharmacological properties. Different pathways tested by us to obtain this glycoside are summarized here. Moreover, the synthesis of N-alkyl and N,N-dialkyl derivatives of the glucopyranoside is presented. Evaluation of antibacterial and antifungal activities of these derivatives indicates that they have no inhibitory activity against Gram-negative bacteria, whereas many of the tested N-alkyl saponins were found to inhibit the growth of Gram-positive bacteria and human pathogenic fungi.

DFT studies of the conversion of four mesylate esters during reaction with ammonia.

AbstractThe energetics of the Menshutkin-like reaction between four mesylate derivatives and ammonia have been computed using B3LYP functional with the 6-31+G** basis set. Additionally, MPW1K/6-31+G** level calculations were carried out to estimate activation barrier heights in the gas phase. Solvent effect corrections were computed using PCM/B3LYP/6-31+G** level. The conversion of the reactant complexes into ion pairs is accompanied by a strong energy decrease in the gas phase and in all solvents. The ion pairs are stabilized with two strong hydrogen bonds in the gas phase. The bifurcation at C2 causes a significant activation barrier increase. Also, bifurcation at C5 leads to noticeable barrier height differentiation. Both B3LYP/6-31+G** and MPW1K/6-31+G** activation barriers suggest the reaction 2 (2a + NH3) to be the fastest in the gas phase. The reaction 4 is the slowest one in all environments. FigureAmmonium salt formation in a Menshutkin-like reaction between ammonia and (S)-1,4-andydro-2,3-dideoxy-5-O-mesylpentitol (2a)

Acetylated methyl 1,2-dideoxyhex-1-enopyranuronates in density functional theory conformational studies.

Geometry optimizations at the B3LYP level and single point calculations at the MP2 level are reported for the (4)H(5) and (5)H(4) conformations of methyl 3,4-di-O-acetyl-1,2-dideoxy-d-arabino-hex-1-enopyranuronate (methyl 3,4-di-O-acetyl-D-glucuronal), and methyl 3,4-di-O-acetyl-1,2-dideoxy-D-lyxo-hex-1-enopyranuronate (methyl 3,4-di-O-acetyl-D-galacturonal). Energy and geometry parameters are presented for the most stable optimized geometries. Conformational analysis of the acetoxy and methoxycarbonyl groups as well as the 1,2-unsaturated pyranoid ring is performed. It is demonstrated that both the acetoxy and methoxycarbonyl groups are planar and prefer cis over trans orientations with respect to the CO-O bond rotations. With regard to the AcO-R bond rotations some of the orientations are forbidden. The (4)H(5)⇌(5)H(4) conformational equilibrium in both methyl 3,4-di-O-acetyl-D-glucuronal (shifted towards (5)H4) and methyl 3,4-di-O-acetyl-D-galacturonal (shifted towards (4)H(5)) is the outcome of the competition between the vinylogous anomeric effect and quasi 1,3-diaxial interactions. It is demonstrated that the orientation of the 4-OAc group influences the strength of the quasi 1,3-diaxial interactions between 3-OAc and 5-COOCH(3) groups. Theoretical results are compared with assignments based on (1)H NMR studies.

Acid-catalyzed isomerization of methyl 2-deoxy-D-arabino-hexosides: equilibria, kinetics and mechanism.

Four isomers of methyl 2-deoxy-D-arabino-hexosides were isolated by HPLC as chromatographically homogeneous compounds. The rates of pyranoside isomerization (alpha(p) and beta(p)) at 40 degrees C and of furanoside isomerization (alpha(f) and beta(f)) at 26 degrees C were determined. A mechanism has been suggested for transformations taking place during isomerization of methyl 2-deoxy-D-arabino-hexosides in methanolic solution catalyzed with hydrogen chloride.

The conformational behavior, geometry and energy parameters of Menshutkin-like reaction of O-isopropylidene-protected glycofuranoid mesylates in view of DFT calculations.

The formation of pyridinium salts in the transformation of three O-isopropylidene-protected mesylates of furanoid sugar derivatives under pyridine action is considered at the B3LYP/6-31+G** computation level. All the structures were optimized in the gas phase, in chloroform and water. Activation barrier heights in the gas phase were also estimated at the B3LYP/6-311++G**, MPW1K/6-31+G** and MPW1K/6-311++G** levels. The conducted calculations, both in the gas phase (regardless of the computation level) and in solvents, revealed the barrier height increasing order as follows: 1>2>3 for the three reactions studied. The conformational behavior of the five-membered ring is discussed in the gas phase and in solvents. The fused dioxolane ring makes the furanoid ring less likely to undergo conformational changes. In the case of reaction 3, the furanoid ring shape does not change either in the gas phase or in solvents. All conformers are close to E0 or (0)E.

Preparation, chemical and crystal structures of N-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)pyridinium chloride

Preparation and isolation of N-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl)pyridinium chloride are described. Its structure was determined by 1H NMR spectroscopy and X-ray analysis. X-ray crystallography revealed that the salt crystallizes with one molecule of water. Ab initio calculations were used to determine charges on atoms in the cation of the title compound.

DFT studies of conversion of methyl chloride and three substituted chloromethyl tetrahydrofuran derivatives during reaction with trimethylamine

AbstractB3LYP/6-31+G** level computations were performed for the formation of four trimethylammonium salts in the reaction of methyl chloride (1a), (S)-1,4-andydro-5-chloro-2,3,5-trideoxypentitol (2a), (2S,5S)-2,5-andydro-6-chloro-1,3,4,6-tetradeoxyhexitol (3a) and methyl 5-chloro-2,3,5-trideoxy-β-D-pentofuranoside (4a) with trimethylamine. All the structures were fully optimized in the gas phase, in chloroform and water. In addition, B3LYP/6-311++G** and MPW1K/6-31+G** level calculations were carried out to estimate activation barrier heights in the gas phase. A detailed description of all stationary points is presented, and the conformational behavior of the THF ring is discussed. B3LYP and MPW1K activation barriers indicate the reaction between methyl chloride and trimethylamine to be the fastest, whereas reaction 4 is the slowest one, both in the gas phase and in solvents. THF ring conformation changes were observed for reactions 2 and 3 along the reaction pathway, whereas it was almost unchanged for reaction 4, in the gas phase. In the case of reactions 2 and 3, different shapes of the THF ring were found for the transition state geometry in the gas phase and in water. The 5E→E4 and 3E→E5 conformational changes were observed for reactions 2 and 3, respectively. Graphical abstractReactions of the formation of quaternary ammonium salts

Molecular and crystal structures of N-(β-d-galactopyranosyl)pyridinium bromide and its per-O-acetylated derivative

1H NMR spectroscopy and X-ray diffraction data are described for N-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)pyridinium bromide and N-(beta-D-galactopyranosyl)pyridinium bromide. X-ray crystallography revealed that the O-acetylated salt crystallizes with two molecules of water and one molecule of ethanol.