Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives.

The new chiral ligands I-III based on derivatives of imidazolidin-4-one were synthesised and characterised. The catalytic activity and enantioselectivity of their corresponding copper(II) complexes were studied in asymmetric Henry reactions. It was found that the enantioselectivity of these catalysts is overall very high and depends on the relative configuration of the ligand used; cis-configuration of ligand affords the nitroaldols with major enantiomer S- (up to 97% ee), whereas the application of ligands with trans-configuration led to nitroaldols with major R-enantiomer (up to 96% ee). The "proline-type" ligand IV was also tested in asymmetric aldol reactions. Under the optimised reaction conditions, aldol products with enantioselectivities of up to 91% ee were obtained.

Immobilization of Trifluoromethyl-Substituted Pyridine-Oxazoline Ligand and Its Application in Asymmetric Continuous Flow Synthesis of Benzosultams.

This study presents an improved synthetic route to ligand (S)-4-(tert-butyl)-2-(5-(trifluoromethyl)pyridin-2-yl)-4,5-dihydrooxazole and its application as a highly active and enantioselective catalyst in the addition of arylboronic acids to cyclic N-sulfonylketimines. Immobilization of such a ligand was achieved using a commercially available starting material and a PS-PEG TentaGel S NH2 support, resulting in a stable heterogeneous catalyst. Although the anchored catalyst exhibited a slight reduction in enantioselectivity and a 4-fold decrease in reaction rate, it displayed remarkable stability, enabling 10 consecutive reaction cycles. Furthermore, the successful transition to a continuous flow system demonstrated even higher turnover numbers compared to batch arrangements. These findings provide valuable insights into the development of efficient flow reactors for continuous synthesis of benzosultams, further advancing the field of asymmetric catalysis.

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban.

The human drugs - the antibiotic linezolid (1) and the anticoagulant rivaroxaban (2) - belong among modern pharmaceutics, which contain an oxazolidine-2-one moiety bearing a stereogenic center. The chirality of these drugs is a fundamental attribute for their biological activity. Herein, one of the efficient asymmetric syntheses of these drugs was studied in detail. Highly enantioselective catalysts were tested in the key step of the synthetic procedure, i.e., the asymmetric Henry reaction, under different reaction conditions, using several starting aldehydes. The corresponding nitroaldols as chiral intermediates in the syntheses of these drugs were obtained in high yields and enantiomeric excesses of up to 91% ee.

Synthesis and characterization of new inhibitors of cholinesterases based on N-phenylcarbamates: In vitro study of inhibitory effect, type of inhibition, lipophilicity and molecular docking.

Based on current treatment of Alzheimer's disease, where the carbamate inhibitor Rivastigmine is used, two series of carbamate derivatives were prepared: (i) N-phenylcarbamates with additional carbamate group (1-12) and (ii) N-phenylcarbamates with monosaccharide moiety (13-24). All compounds were tested for the inhibitory effect on both of the cholinesterases, electric eel acetylcholinesterase (eeAChE) and butyrylcholinesterase from equine serum (eqBChE) and the inhibitory activity (expressed as IC50 values) was compared with that of the established drugs Galanthamine and Rivastigmine. The compounds with two carbamate groups 1-12 revealed higher inhibitory efficiency on both cholinesterases in compared with monosaccharide derived carbamates 13-24 and with Rivastigmine. The significant decrease of inhibitory efficiency on eqBChE (also for eeAChE but in less manner) was observed after deacetalization of monosaccharide. Moreover, the type of inhibitory mechanism of five chosen compounds was studied. It was found, that compounds with two carbamate groups act presumably via a mixed inhibitory mechanism and the compounds with monosaccharide moiety act as non-competitive inhibitors. The lipophilicity of tested compounds was determined using partition coefficient. Specific positions of the inhibitors in the binding sites of cholinesterases were determined using molecular modeling and the results indicate the importance of phenylcarbamate orientation in the catalytic gorges of both enzymes.

Recent Advances in C-C and C-N Bond Forming Reactions Catalysed by Polystyrene-Supported Copper Complexes.

This present mini-review covers recently published results on Cu(I) and Cu(II) complexes immobilized on polystyrene carriers, which are used as heterogeneous, eco-friendly reusable catalysts applied for carbon-carbon and carbon-nitrogen forming reactions. Recent advances and trends in this area are demonstrated in the examples of oxidative homocoupling of terminal alkynes, the synthesis of propargylamines, nitroaldolization reactions, azide alkyne cycloaddition, N-arylation of nitrogen containing compounds, aza-Michael additions, asymmetric Friedel-Crafts reactions, asymmetric Mukaiyama aldol reactions, and asymmetric 1,3-dipolar cycloaddition of azomethine ylides. The type of polystyrene matrix used for the immobilization of complexes is discussed in this paper, and particularly, the efficiency of the catalysts from the point of view of the overall reaction yield, and possible enantioselectivity and potential reusing, is reviewed.

Synthesis, characterization and in vitro evaluation of substituted N-(2-phenylcyclopropyl)carbamates as acetyl- and butyrylcholinesterase inhibitors.

A serie of O-substituted N-2-phenylcyclopropylcarbamates was prepared and characterized. These carbamates were tested as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). It was found, that these compounds exhibit moderate inhibition activity with values of IC50 in the range of 54.8-94.4 µM (for AChE) and up to 5.8 µM (for BChE). The AChE/BChE selectivity for each carbamate was calculated. These values varied from 0.50 to 9.46, two carbamate derivatives inhibited only AChE selectively. The most promising derivative was prepared in all optically pure forms (four isomers). It was found that individual stereoisomers differed only slightly in the inhibition ability. The cytotoxicity of all carbamates was evaluated using the standard in vitro test with Jurkat cells. With regard to their inhibition activity and cytotoxicity as well as easy preparation, O-substituted N-2-phenylcyclopropylcarbamates can be considered as promising compounds for potential medicinal applications.

Highly enantioselective nitroaldol reactions catalyzed by copper(II) complexes derived from substituted 2-(pyridin-2-yl)imidazolidin-4-one ligands.

Ten optically pure substituted 2-(pyridin-2-yl)imidazolidin-4-ones, 1a-d, 2a-4a, and 2b-4b, were prepared and characterized. The absolute configurations of individual ligands were determined by X-ray analysis or NOESY experiments. The Cu(II) complexes of the respective ligands were studied as enantioselective catalysts of the nitroaldol (Henry) reaction of aldehydes with nitromethane, giving the corresponding substituted 2-nitroalkanols. In the case of an anti arrangement of the imidazolidin-4-one ring, the obtained result was 91-96% ee, whereas in the case of syn arrangement, a significant drop to 25-27% ee was observed.

(3RS)-S-[1-(3-Chloro-phen-yl)-2-oxopyr-roli-din-3-yl]thio-uronium bromide.

In the title molecular salt, C(11)H(13)ClN(3)OS(+)·Br(-), the C-N bond lengths in the -S-C(NH(2))(2) fragment indicate partial double-bond character of these bonds. The constituent ions are connected by N-H⋯Br bridges into Z-shaped chains. The supra-molecular architecture of the structure can be described by being composed of these chains inter-locked by additional C-H⋯Br short contacts. An intra-molecular N-H⋯O=C bridge, as well as weak C-H⋯O hydrogen bonds, are also present in the structure.

(3RS)-S-[1-(3-Chloro-phen-yl)-2-oxopyr-rolidin-3-yl]-N,N'-dimethyl-thio-uronium bromide.

The title mol-ecule, C(13)H(17)ClN(3)OS(+)·Br(-), consists of benzene and pyrrolidine rings and an S-C(NHCH(3))(2) group. The central C-N bond lengths in the S-C(NHCH(3))(2) fragment indicate partial double-bond character. Mol-ecules are inter-connected into chains by N-H⋯Br hydrogen bonds and the chains are linked into pairs by weak C-H⋯Br hydrogen bonds.

New targeting system for antimycotic drugs: beta-glucosidase sensitive amphotericin B-star poly(ethylene glycol) conjugate.

A new targeting potentially intravenous conjugate Amphotericin B (AMB)-star poly(ethylene glycol) (sPEG) (M=25,160) has been synthesized and characterized. It contains a beta-d-glucopyranoside molecular switch which is sensitive to beta-glucosidases (E.C.3.2.1.21). The beta-glucosidase-catalyzed release of AMB from the polymeric carrier was proved in vitro by means of spectrophotometry and HPLC.