Piotr Kiełbasiński

Enzymatic reactions in ionic liquids: lipase-catalysed kinetic resolution of racemic, P-chiral hydroxymethanephosphinates and hydroxymethylphosphine oxides

Abstract Lipase-mediated acetylation of racemic P -chiral hydroxymethanephosphinates and hydroxymethylphosphine oxides was performed in ionic liquids under kinetic resolution conditions. Lipase AK (Amano) and lipase from Pseudomonas fluorescens (Fluka) were up to six times more enantioselective in BMIM·PF 6 solutions than in common organic solvents. On the contrary, the analogous reactions performed in BMIM·BF 4 were practically non-stereoselective.

LIPASE-PROMOTED KINETIC RESOLUTION OF RACEMIC, P-CHIRAL HYDROXYMETHYLPHOSPHONATES AND PHOSPHINATES

Abstract Lipase-mediated acetylation of racemic P-chiral hydroxymethylphosphonates and phosphinates, and hydrolysis of their O -acetyl derivatives have been conducted under kinetic resolution conditions to give the enantiomerically enriched title products with up to 92% ee. Their absolute configuration has been determined by means of chemical correlation and CD measurements.

Chiral Organosulfur Ligands/Catalysts with a Stereogenic Sulfur Atom: Applications in Asymmetric Synthesis

Asymmetric synthesis, in which chiral organocatalysts or metal complexes with chiral ligands are used, has become the most valuable methodology for the preparation of enantiomerically pure organic compounds. Among such catalysts/ligands, a growing number constitute various organosulfur compounds. This Review provides comprehensive and critical information on the plethora of sulfur-based chiral ligands and organocatalysts used in asymmetric synthesis, which have been published within the last 15 years. However, it is confined to the presentation of only those chiral catalysts/ligands that possess a stereogenic sulfur atom and includes sulfoxides, sulfinamides, N-sulfinyl ureas, sulfoximines, and some related S-chiral derivatives.

Biocatalytic syntheses of chiral non-racemic 2-hydroxyalkanephosphonates

A series of 2-oxoalkanephosphonates 2 were screened for reduction with Geotrichum candidum. Only diethyl 2-oxopropanephosphonate 2a underwent asymmetric reduction to give (+)-(R)-diethyl 2-hydroxypropanephosphonate 3a with 98% e.e. In turn, a series of racemic 2-hydroxyalkanephosphonates 3 were acetylated under kinetic resolution conditions in the presence of various lipases to give the corresponding 2-acetoxyalkanephosphonates 4 and recovered alcohols 3 in good yields and with e.e. up to 93%.

A new synthesis of (±)-sarkomycin from a β-ketophosphonate

Abstract The total synthesis of (±)-sarkomycin starting from diethyl 2-oxopropanephosphonate is reported. The key step in this synthesis includes the Horner-Wittig reaction of 2-diethoxy-phosphoryl-3-carboxy-cyclopentanone with formaldehyde

Enzyme-promoted kinetic resolution of racemic, P-chiral phosphonyl and phosphorylacetates

Abstract A series of racemic methyl phosphonyl- and phosphorylacetates were hydrolyzed in the presence of porcine liver esterase (PLE) under kinetic resolution conditions to give the corresponding P-chiral phosphonyl- and phosphorylacetic acids and recovered esters in moderate to high enantiomeric purity (up to 95% ee). The Jones PLE active site model was applied to explain the enantioselectivity of this reaction.

The Comparison of MTT and CVS Assays for the Assessment of Anticancer Agent Interactions.

Multiple in vitro tests are widely applied to assess the anticancer activity of new compounds, including their combinations and interactions with other drugs. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay is one of the most commonly used assays to assess the efficacy and interactions of anticancer agents. However, it can be significantly influenced by compounds that modify cell metabolism and reaction conditions. Therefore, several assays are sometimes used to screen for potential anticancer drugs. However, the majority of drug interactions are evaluated only with this single method. The aim of our studies was to verify whether the choice of an assay has an impact on determining the type of interaction and to identify the source of discrepancies. We compared the accuracy of MTT and CVS (crystal violet staining) assays in the interaction of two compounds characterized by similar anticancer activity: isothiocyanates (ITCs) and Selol. Confocal microscopy studies were carried out to assess the influence of these compounds on the reactive oxygen species (ROS) level, mitochondrial membrane potential, dead-to-live cell ratio and MTT-tetrazolium salt reduction rate. The MTT assay was less reliable than CVS. The MTT test of Selol and 2-oxoheptyl ITC, which affected the ROS level and MTT reduction rate, gave false negative (2-oxoheptyl ITC) or false positive (Selol) results. As a consequence, the MTT assay identified an antagonistic interaction between Selol and ITC, while the metabolism-independent CVS test identified an additive or synergistic interaction. In this paper, we show for the first time that the test assay may change the interpretation of the compound interaction. Therefore, the test method should be chosen with caution, considering the mechanism of action of the compound.

Highly Efficient Asymmetric Simmons–Smith Cyclopropanation Promoted by Chiral Heteroorganic Aziridinyl Ligands

Enantiomerically pure heteroorganic catalysts, bearing a hydroxy moiety, a stereogenic sulfinyl group, and a chiral aziridine moiety, have proved highly efficient in the asymmetric Simmons–Smith cyclopropanation of allylic alcohols, which generates the desired products in high yields (up to 95 %) and with ee values up to 94 %. The effect of the stereogenic centers at the sulfinyl sulfur atom and in the aziridine moiety on the stereochemical course of the title reaction is discussed.

Biocatalysis in Organosulfur Chemistry

Abstract Enzymes, which are very efficient catalysts developed by nature to control chemical transformations in vivo, are also capable of adopting non-natural substrates, among them heteroorganic derivatives, and are also capable of working in non-aqueous media. Being intrinsically chiral, enzymes recognize any type of chirality of the substrates. This feature has been utilized for the stereoselective transformations of a variety of organosulfur compounds, resulting in the preparation of chiral non-racemic sulfur products.

Enzymatic resolution of racemic phosphinoylacetates having a stereogenic phosphorus atom

Abstract A series of racemic methyl alkylphenylphosphinoylacetates was hydrolyzed in the presence of pig liver esterase (PLE) to give the corresponding P-chiral phosphinoylacetic acids and unreacted esters in a high enantiomeric purity (72–100% ee).