Stanisław Witkowski

Glycosidic moiety changes the spectroscopic properties of DL-α-tocopherol in DMSO/water solution and in organic solvents

In this study we estimated how conjugation with a sugar moiety influences the spectral properties of tocopherol and relate the spectroscopic properties of glycosides to solvent properties such as viscosity and polarity. Spectroscopic properties (absorption, fluorescence, fluorescence anisotropy and fluorescence lifetime) of three dl-alpha-tocopheryl glycosides (dl-alpha-tocopheryl orthoacetate derivative and glycosides of dl-alpha-tocopherol model compounds: 2,2,5,7,8-pentamethyl-6-chromanol and Trolox) were studied in DMSO/water solution. In all investigated compounds dissolved in DMSO/water mixture the absorption and emission maxima were blue-shifted. The fluorescence lifetimes were longer compared with those obtained for the parent compounds, except for the Trolox glucoside, in which it was shorter. The observed effect is connected with an increase in the electronic energy in the ground state due to electron rearrangement in the chromanol system caused by interaction with the sugar moiety. The extent of the spectral shift is related to the sugar moiety substituted at the phenolic oxygen rather than to substitution at the 2a position in the chromanol ring. The fluorescent properties of dl-alpha-tocopheryl glucoside in organic solvents were measured. The Stokes shift was related to the orientational polarizability of the solvents. The study of viscosity suggested two different mechanisms explaining the results observed in a low- and high-viscosity environment. The results indicated the fundamental role of interactions between the chromophore and sugar moiety in a low-viscosity environment. The results obtained at high values of viscosity are discussed in terms of a frictional boundary solvent-solute interaction model.

Partition of tocopheryl glucopyranoside into liposome membranes studied by fluorescence methods.

Vitamin E is poorly soluble in aqueous solutions. Enhanced physiological activity is expected from synthesized glycosidic tocopherol derivatives. We investigated binding, location and interactions of newly synthesized DL-alpha-tocopheryl beta D glucopyranoside (II) in phosphatidylcholine liposomes using fluorescence emission, anisotropy and lifetime methods. In liposomes emission maximum and fluorescence lifetime of glucoside were similar to those observed in methanol. High fluorescence anisotropy value indicates that tocopheryl glucoside is located in restricted mobility region of the membrane. Thermodynamic calculation indicated efficient partition of (II) into membrane. The energy minimization calculations of electrostatic potential distribution of (II) and solvation energies performed with Gaussian program confirmed strong affinity of glucosidic moiety for ionic interactions and supported proposed model of interactions. The all obtained data indicate that DL-alpha-tocopheryl beta-glucoside is embedded into the membrane interior whereas sugar moiety protrudes above the water/lipid interface of the membrane surface.

Hindered Rotation in New Air-Stable Ruthenium Olefin Metathesis Catalysts with Chromanylmethylidene Ligands

Three new ruthenium complexes with chromanylmethylidene ligands were synthesized and dynamic NMR analysis of these compounds was carried out. The activation energy for the C–Ru rotation was measured for the first time and found to be of ~60 kJ mol–1. The complexes may potentially serve as latent catalysts for olefin metathesis – they promote the simple ring-closing metathesis reactions very slowly at room temperature, but are much more active at slightly elevated temperatures. No asymmetric induction was observed when the chiral α-tocopherol-derived catalyst was used.

A selective electrochemical method of glycosylation of 3β-hydroxy-Δ5-steroids

A new electrochemical glycosylation method is presented. According to the method cholesterol and other 3beta-hydroxy-Delta(5)-steroids can be selectively transformed to glycosides using non-activated sugars. The method is also useful for the synthesis of glycoconjugates with sugar linked to a steroid moiety by an ether bond.

Studies in the acid catalysed glycosylation of α-tocopherol

Condensation of α-tocopherol and 2,2,5,7,8-pentamethyl-6-hydroxychroman (the model compound) with peracetylated glucose, mannose and galactose was carried out. The influence of various acidic catalysts on the chemical yield and the stereochemical outcome of the glycosylation was investigated.

Synthesis of α-Tocopheryl Glycosides

Abstract An unusual course of d-α-tocopherol glucosylation by the Helferich method was observed. The product distribution very depended on acid catalyst and solvent used. The β-glucoside was accompanied by an unsaturated α-glucoside. Other unsaturated d-α-tocopheryl glucosides were obtained by reactions with acetylated glucal and 2-acetoxy glucal.

Multi-conformer molecules in solutions: an NMR-based DFT/MP2 conformational study of two glucopyranosides of a vitamin E model compound

Overall conformations of both anomeric per-O-acetylated glucosyl derivatives of 2,2,5,7,8-pentamethylchroman-6-ol were studied in the context of their high flexibility, on the basis of NMR spectra in CDCl3 solution and related DFT calculation results. A few computational protocols were used, including diverse density functional/basis set combinations with a special emphasis on accounting (at various steps of the study) for the impact of intramolecular London-dispersion (LD) effects on geometries and relative Gibbs free energies (ΔGs) of different conformers coexisting in solution. The solvent effect was simulated by an IEF-PCM approach with the UFF radii; its other variants, including the use of the recently introduced IDSCRF radii, were employed for a few compact B3LYP-GD3BJ optimized structures showing one small imaginary vibrational frequency. The advantage of using IDSCRF radii for such purposes was shown. Of the four tested DFT methods, only the application of the B3LYP/6-31+G(d,p) approximation afforded ensembles of 7-8 single forms for which population-average values of computed NMR parameters (δH, δC and some (n)JHH data) were in close agreement with those measured experimentally; binuclear (δH,C 1 : 1) correlations, rH,C(2) = 0.9998. The associated individual ΔG values, corrected for LD interactions by applying Grimmes DFT-D3 terms, afforded relative contents of different contributors to the analyzed conformational families in much better agreement with pertinent DFT/NMR-derived populations (i.e., both data sets were found to be practically equal within the limits of estimated errors) than those calculated from dispersion uncorrected ΔGs. All these main findings were confirmed by additional results obtained at the MP2 level of theory. Various other aspects of the study such as the crystal vs. solution structure, gg/gt rotamer ratio, diagnostic (de)shielding effects, dihydrogen C-H···H-C contacts, and doubtful applicability of some specialized DFT functionals (M06-2X, ωB97X-D and B3LYP-GD3BJ) for the description of highly flexible molecules are also discussed in detail.

New indenylidene-type metathesis catalysts bearing unsymmetrical N-heterocyclic ligands with mesityl and nitrobenzyl substituents

New indenylidene-type second generation catalysts bearing modified unsymmetrically substituted N-heterocyclic carbene ligands were synthesized. The complexes contain an N-mesityl and N′-nitrobenzyl substituted NHC ligand. The precursors of free carbenes—imidazolinium salts—were obtained in an easy and environment-friendly way (under aqueous or neat conditions). The new catalysts were prepared by reaction of in situ generated carbenes with a 1st generation indenylidene catalyst, containing pyridine ligands instead of tricyclohexylphosphine. The complexes were tested in RCM, CM, and ene-yne metathesis model reactions in commercial-grade solvents in air. Their activities were compared with that of commercially available indenylidene catalyst. The structures of complexes and their stability were investigated using static DFT calculations with mixed basis set.Graphical abstract

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand.

Summary The synthesis of a new type of Hoveyda–Grubbs 2nd generation catalyst bearing a modified N-heterocyclic carbene ligands is reported. The new catalyst contains an NHC ligand symmetrically substituted with chromanyl moieties. The complex was tested in model CM and RCM reactions. It showed very high activity in CM reactions with electron-deficient α,β-unsaturated compounds even at 0 °C. It was also examined in more demanding systems such as conjugated dienes and polyenes. The catalyst is stable, storable and easy to purify.

2,2,5,7,8-Penta­methyl­chroman-6-yl 2,3,4,6-tetra-O-acetyl-α-d-glucopyran­oside from synchrotron data

The crystal structure of the title compound, C28H38O11, solved and refined against synchrotron diffraction data, contains two formula units in the asymmetric unit. In both molecules, the dihydropyran ring along with its methyl substituents is disordered and adopts two alternative half-chair conformations. The occupancy of the major conformers of the two molecules refined to 0.858 (5) and 0.523 (5).