Reko Leino

Acyl Group Migration and Cleavage in Selectively Protected β-d-Galactopyranosides as Studied by NMR Spectroscopy and Kinetic Calculations

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.

Pros and cons of using resazurin staining for quantification of viable Staphylococcus aureus biofilms in a screening assay

Staining of Staphylococcus aureus biofilms with 20 microM resazurin during 20 min was shown to provide a good screening assay in 96-well micro titer plates. However, data quality was found to be dependent on the staining duration and biofilm concentration. Also, the inadequacy of using resazurin calibration curves with planktonic cells to estimate S. aureus biofilm concentrations was demonstrated.

Batchwise and continuous enantioselective hydrogenation of 1-phenyl-1,2-propanedione catalyzed by new Pt/SiO2 fibers

Abstract A new knitted silica fiber was investigated as a support material in enantioselective hydrogenation of 1-phenyl-1,2-propanedione in a pressurized batch reactor. The active metal was platinum and the catalyst was modified in situ with (−)-cinchonidine. The catalysts were prepared by impregnation method using hexachloroplatinic acid as metal precursor. The main experimental parameters were the support calcination temperature and the metal loading of the catalyst. The optimum catalyst dispersion, BET specific surface area and mean Pt particle size for enantio-differentiation were measured. A comparison of alumina and silica supports revealed that the main parameters in the enantio-differentiation were the mean metal particle size and the metal dispersion. Optimal metal particle size and dispersion were detected which optimize the enantioselection. Experiments with continuously operated fixed bed reactor demonstrated that continuous hydrogenation, over the new knitted silica fiber catalyst, gives equally high enantiomeric excesses compared to the batch operation. Continuous operation can be used as tool to study catalyst deactivation and reaction mechanisms in enantioselective hydrogenation.

Copolymerization of ethene with 1-hexene or 1-hexadecene over ethylene, dimethylsilylene and 1,4-butanediylsilylene bridged bis(indenyl) and bis(tetrahydroindenyl) zirconium dichlorides

Ethene was copolymerized with 1-hexene and 1-hexadecene over five different homogeneous methylaluminoxane (MAO) activated racemic ansa-metallocene catalysts in order to study both the influence of the ligand (indenyl and tetrahydroindenyl) and the influence of the interannular bridge (ethylene, dimethylsilylene and 1.4.-butanediylsilylene) on the copolymerization behaviour. Hydrogenation of the indenyl ligands was found to decrease comonomer content and molar mass of the copolymers. A similar tendency was observed for the ethylene bridge compared to the silylene bridges. The reasons for this behaviour are discussed and related to structural differences of the catalyst precursors. In addition a segregation fractionation technique was applied to study the chemical composition distribution (CCD) of the produced copolymers. Batchwise feed of comonomer resulted in a broad CCD. More homogeneous copolymers could be produced using partly continuous feed of comonomer.

Hydrosilylation of cinchonidine and 9-O-TMS-cinchonidine with triethoxysilane: application of 11-(triethoxysilyl)-10,11-dihydrocinchonidine as a chiral modifier in the enantioselective hydrogenation of 1-phenylpropane-1,2-dione

The detailed synthesis and characterization of (−)-11-(triethoxysilyl)-10,11-dihydrocinchonidine (4), a starting material for the immobilization of (−)-cinchonidine on silica based supports, is described. Compound 4 together with its precursors 9-O-(trimethylsilyl)cinchonidine (2) and 9-O-(trimethylsilyl)-11-(triethoxysilyl)-10,11-dihydrocinchonidine (3) were employed as chiral modifiers in the hydrogenation of a prochiral diketone, 1-phenylpropane-1,2-dione, over a heterogeneous Pt/Al2O3 catalyst using cinchonidine (1) as a reference modifier. The unexpected enhancement of ee induced by 4, demonstrating the positive effect of distal modifier substitution, is discussed in the light of molecular modeling and NMR studies.

L-Pentoses in biological and medicinal applications.

2.2. Antibacterial and Antifungal Compounds 3339 2.2.1. Aminoglycoside Antibiotics 3339 2.2.2. Orthosomycin Antibiotics 3342 2.2.3. Pradimicin Antibiotics 3343 2.2.4. Antibacterial and Antifungal Compounds Reported in the Patent Literature Only 3344 2.3. Antineoplastic Compounds 3344 2.3.1. Alkylating Agents 3344 2.3.2. Protein Kinase Inhibitors 3346 2.3.3. Anticancer Antibiotics 3346 2.3.4. Plant Saponins 3348 2.3.5. Anticancer Agents Reported in the Patent Literature Only 3352 3. Conclusions 3352 Author Information 3352 Biographies 3352 Acknowledgment 3353 References 3353

Heterogeneous Chemoenzymatic Catalyst Combinations for One‐Pot Dynamic Kinetic Resolution Applications

Heterogeneously catalyzed one‐pot reactions combining individual reaction steps into sequences enhance the efficiencies of overall chemical processes by reducing costs, time, and labor efforts. This minireview focuses on the production of chiral compounds by using dynamic kinetic resolution (DKR) and related sequential reactions, utilizing heterogeneous and immobilized metal catalysts and enzymes. Enzymes, especially lipases, often possess high chemical, stereo‐, and regiospecificities under mild reaction conditions. Supported transition‐metal catalysts are effective and widely used for various chemical transformations including racemization and hydrogenation reactions. This minireview discusses both the early and important applications, as well as modern state‐of‐the‐art processes, in which different catalyst combinations are utilized. Also catalyst compatibility issues, including catalyst inhibition and applicability are addressed with specific focus on the racemization catalysts applied in DKRs. Finally, some examples on the utilization of heterogeneous catalysts in flow reactors are presented.

A combined NMR, DFT, and X-ray investigation of some cinchona alkaloid O-ethers.

Structures and conformational behavior of several cinchona alkaloid O-ethers in the solid state (X-ray), in solution (NMR and DFT), and in the gas phase (DFT) were investigated. In the crystal, O-phenylcinchonidine adopts the Open(3) conformation similar to cinchonidine, whereas the O-methyl ether derivatives of both cinchonidine and cinchonine are packed in the Closed(1) conformation. Dynamic equilibria in solutions of the alkaloids were revealed by combined experimental-theoretical spin simulation/iteration techniques for the first time. In the (1)H NMR spectra in CDCl3 and toluene-d8 at room temperature, Closed(1) conformation was observed for the O-silyl ethers as a separate set of signals. For O-methyl ether derivatives Closed(1) could be separated only at -30 degrees C in CDCl3 or toluene-d8 and for O-phenylcinchonidine at -70 degrees C in CDCl3/CD2Cl2. The ratio between the Closed(2) and Open(3) conformers was estimated by analyzing the vicinal coupling constant (3)J(H9,H8) at ambient and low temperatures. The observed conformational equilibria of O-(tert-butyldimethylsilyl)cinchonidine in CDCl 3 and toluene-d8 are in good agreement with the theoretically estimated equilibrium populations of the conformations according to Boltzmann statistics. The conformational equilibria of four cinchona alkaloid O-ether solutes in CDCl3 and toluene-d8 are discussed in the light of their relevance to the mechanism of 1-phenyl-1,2-propanedione (PPD) hydrogenation over cinchona alkaloid modified heterogeneous platinum catalysts. It was demonstrated that the conformation found to be abundant in the liquid phase has no direct correlation with the enantioselectivity of the PPD hydrogenation reaction.

Studies related to Norway spruce galactoglucomannans: chemical synthesis, conformation analysis, NMR spectroscopic characterization, and molecular recognition of model compounds.

Galactoglucomannan (GGM) is a polysaccharide mainly consisting of mannose, glucose, and galactose. GGM is the most abundant hemicellulose in the Norway spruce (Picea abies), but is also found in the cell wall of flax seeds, tobacco plants, and kiwifruit. Although several applications for GGM polysaccharides have been developed in pulp and paper manufacturing and the food and medical industries, attempts to synthesize and study distinct fragments of this polysaccharide have not been reported previously. Herein, the synthesis of one of the core trisaccharide units of GGM together with a less-abundant tetrasaccharide fragment is described. In addition, detailed NMR spectroscopic characterization of the model compounds, comparison of the spectral data with natural GGM, investigation of the acetyl-group migration phenomena that takes place in the polysaccharide by using small model compounds, and a binding study between the tetrasaccharide model fragment and a galactose-binding protein (the toxin viscumin) are reported.

Experimental and Theoretical Analysis of Asymmetric Induction in Heterogeneous Catalysis : Diastereoselective Hydrogenation of Chiral α-Hydroxyketones over Pt Catalyst

Assessing the origin of asymmetric induction in heterogeneously catalyzed hydrogenation is a challenging task. In this work, hydrogenation of a chiral compound, (R)-1-hydroxy-1-phenyl-2-propanone [(R)-PAC], in toluene over cinchonidine modified and unmodified Pt/Al(2)O(3) was studied. To reveal the detailed reaction mechanism and the origin of stereoselectivity in the Pt-catalyzed hydrogenation of the CO double bond, the structures and energies of several adsorption modes of (R)-PAC as well as whole reaction paths for hydrogenation were investigated on Pt(111) by density functional theory (DFT). In agreement with experimental results, the theoretically obtained potential energy profiles for the studied hydrogenation mechanisms implied that (1R,2S)-1-phenyl-1,2-propanediol is formed in excess with respect to the other diastereomeric product diol, (1R,2R)-1-phenyl-1,2-propanediol. Generally, if the elementary hydrogen addition step was thermodynamically more favorable on one of the two diastereotopic faces, it was also kinetically preferred on the same face, and vice versa. Pairwise addition of hydrogen was the most energetically favorable mechanism. Adsorption and hydrogenation of other structurally similar chiral alpha-hydroxyketones, (R)-3-hydroxy-2-butanone and (R)-2-hydroxy-1-cyclohexanone, were also studied computationally on Pt(111). The results showed that cluster model DFT calculations can be used to assess (dia)stereoselectivity in metal-catalyzed hydrogenation of even such complex organic molecules as studied here.