Mystery of the Passerini Reaction for the Synthesis of the Antimicrobial Peptidomimetics against Nosocomial Pathogenic Bacteria.

The first example of applying salicylaldehyde derivatives, as well as coumarin with the formyl group at the C8 position in its structure, as carbonyl partners in a three-component Passerini reaction, is presented. As a result of research on the conditions of the Passerini reaction, the important role of the hydroxyl group in the salicylaldehyde used in the course of the multicomponent reaction was revealed. When an aldehyde with an unprotected hydroxyl group is used, only two-component α-hydroxy amide products are obtained.

The Influence of Ligands on the Pd-Catalyzed Diarylation of Vinyl Esters.

The impact of ligands on the palladium-catalyzed 1,2-diarylation reaction course is presented. The application of Pd-dmpzc as a catalyst provides an efficient, chemoselective and sustainable protocol for the synthesis of valuable 1,2-diphenylethyl acetates. The reaction is conducted in water under mild conditions.

Evaluation of Antibacterial Activity against Nosocomial Pathogens of an Enzymatically Derived α-Aminophosphonates Possessing Coumarin Scaffold.

The purpose of the present study was to evaluate the synergistic effect of two important pharmacophores, coumarin and α-amino dimethyl phosphonate moieties, on antimicrobial activity against selected strains of multidrug-resistant nosocomial pathogenic bacteria. The previously developed enzyme-catalysed Kabachnik-Fields protocol allowed us to obtain the studied compounds with high yields which were free from metal impurities. The structure-activity relationship revealed that inhibitory activity is strongly related to the presence of the trifluoromethyl group (CF-) in the coumarin scaffold.

Interdisciplinary approach to synthesis, stability and antimicrobial activity of silver nanoparticles.

Introduction: Chronic wounds are an increasing problem for health care all over the world. New treatment options for this illness are desired, especially antimicrobial agents. Silver nanoparticles (AgNPs) can be a potential substance that may be used in treatment of chronic wounds due to the growing antibiotic resistance.

Enzymatic Synthesis of a Novel Coumarin Aminophosphonates: Antibacterial Effects and Oxidative Stress Modulation on Selected Strains.

The objective of the present study was to evaluate the synergistic effect of two important pharmacophores, coumarin and α-amino dimethyl phosphonate moieties, on antimicrobial activity toward selected LPS-varied strains. Studied antimicrobial agents were prepared a Kabachnik-Fields reaction promoted by lipases. The products were provided with an excellent yield (up to 92%) under mild, solvent- and metal-free conditions.

Synthesis and Antimicrobial Activity of the Pathogenic Strains of -Quinols: Additive Effects of Copper-Catalyzed Addition of Aryl Boronic Acid to Benzoquinones.

A mild and efficient protocol for the synthesis of -quinols under aqueous conditions was developed. The pivotal role of additives in the copper-catalyzed addition of aryl boronic and heteroaryl boronic acids to benzoquinones was observed. It was found that polyvinylpyrrolidone (PVP) was the most efficient additive used for the studied reaction.

Simultaneous Enantiodivergent Synthesis of Diverse Lactones and Lactams via Sequential One-Pot Enzymatic Kinetic Resolution-Ring-Closing Metathesis Reactions.

One of the goals of diversity-oriented synthesis is to achieve the structural diversity of obtained compounds. As most biologically active compounds are chiral, it is important to develop enantioselective methods of their synthesis. The application of kinetic resolution in DOS is problematic because of low efficiency (max.

The Synthesis and Evaluation of Diethyl Benzylphosphonates as Potential Antimicrobial Agents.

The impact of substituent at phenyl ring of diethyl benzylphosphonate derivatives on cytotoxic activity was studied. The organophosphonates were obtained based on developed palladium-catalyzed α, β-homodiarylation of vinyl esters protocol. The new synthetic pathway toward 1,2-bis(4-((diethoxyphosphoryl)methyl)phenyl)ethyl acetate was proposed which significantly improves the overall yield of the final product (from 1% to 38%).

Promiscuous Lipase-Catalyzed Knoevenagel-Phospha-Michael Reaction for the Synthesis of Antimicrobial β-Phosphono Malonates.

An enzymatic route for phosphorous-carbon bond formation was developed by discovering new promiscuous activity of lipase. We reported a new metal-free biocatalytic method for the synthesis of pharmacologically relevant β-phosphonomalononitriles via a lipase-catalyzed one-pot Knoevenagel-phospha-Michael reaction. We carefully analyzed the best conditions for the given reaction: the type of enzyme, temperature, and type of solvent.

Intensification of Double Kinetic Resolution of Chiral Amines and Alcohols via Chemoselective Formation of a Carbonate-Enzyme Intermediate.

Chiral amines and alcohols are synthons of numerous pharmaceutically-relevant compounds. The previously developed enzymatic kinetic resolution approaches utilize a chiral racemic molecule and achiral acyl donor (or acyl acceptor). Thus, only one enantiodivergent step of the catalytic cycle is engaged, which does not fully exploit the enzyme’s abilities.

Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in . Strains.

An efficient method for the synthesis of functionalized peptidomimetics via multicomponent Ugi reaction has been developed. The application of trifluoroethanol (TFE) as a reaction medium provided desired products with good yields. Further, using the developed cyclisation reaction, the obtained peptidomimetics were transformed into the cyclic analogues (diketopiperazines, DKPs).

Relationship between Structure and Antibacterial Activity of α-Aminophosphonate Derivatives Obtained via Lipase-Catalyzed Kabachnik-Fields Reaction.

We reported a new method dealing with the synthesis of novel pharmacologically relevant α-aminophosphonate derivatives via a lipase-catalyzed Kabachnik−Fields reaction with yields of up to 93%. The advantages of this protocol are excellent yields, mild reaction conditions, low costs, and sustainability. The developed protocol is applicable to a range of H-phosphites and organic amines, providing a wide substrate scope.

Screening for amidoxime reductases in plant roots and Saccharomyces cerevisiae - Development of biocatalytic method for chemoselective amidine synthesis.

The novel biocatalytic method for the synthesis of pharmaceutically relevant N-unsubstituted amidines was presented. The application of whole cells from commonly available vegetables allowed for the chemoselective reduction of the amidoxime moiety in the presence of other substituents prone to reduction or dehalogenation e.g.

Computer-designed repurposing of chemical wastes into drugs.

As the chemical industry continues to produce considerable quantities of waste chemicals, it is essential to devise 'circular chemistry' schemes to productively back-convert at least a portion of these unwanted materials into useful products. Despite substantial progress in the degradation of some classes of harmful chemicals, work on 'closing the circle'-transforming waste substrates into valuable products-remains fragmented and focused on well known areas. Comprehensive analyses of which valuable products are synthesizable from diverse chemical wastes are difficult because even small sets of waste substrates can, within few steps, generate millions of putative products, each synthesizable by multiple routes forming densely connected networks.

Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives.

An enzymatic route for phosphorous-carbon- bond formation is developed by discovering new promiscuous activity of lipase. This biocatalytic transformation of phosphorous-carbon- bond addition leads to biologically and pharmacologically relevant α-acyloxy phosphonates with methyl group in α-position. A series of target compounds were synthesized with yields ranging from 54% to 83% by enzymatic reaction with (CcL) lipase via Markovnikov addition of -phosphites to vinyl esters.

The Evaluation of DHPMs as Biotoxic Agents on Pathogen Bacterial Membranes.

Herein, we present biological studies on 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) obtained via Biginelli reaction catalyzed by NH4Cl under solvent-free conditions. Until now, DHPMs have not been tested for biological activity against pathogenic strains. We tested 16 newly synthesized DHPMs as antimicrobial agents on model strains (K12 and R2-R4).

The Synthesis and Evaluation of Amidoximes as Cytotoxic Agents on Model Bacterial Strains.

The biological research on newly synthesized amidoximes, Boc-protected amidoximes and Boc-derived amidines, obtained by a reduction of the parent amidoximes is reported, herein. Due to the presence of a free amino group in both amidines and amidoximes, these compounds can undergo various chemical reactions such as -alkylation and -acylation. One such reaction is Boc-protection, often used in organic synthesis to protect the amino and imino groups.

The Synthesis and Evaluation of Aminocoumarin Peptidomimetics as Cytotoxic Agents on Model Bacterial Strains.

This work presents the successful synthesis of a library of novel peptidomimetics via Ugi multicomponent reaction. Most of these peptidomimetics contain differently substituted aminocoumarin; 7-amino-4-methylcoumarin and 7-amino-4-(trifluoromethyl) coumarin. Inspired by the biological properties of coumarin derivatives and peptidomimetics, we proposed the synthesis of coumarin incorporated peptidomimetics.

Selective Esterification of Phosphonic Acids.

Here, we report straightforward and selective synthetic procedures for mono- and diesterification of phosphonic acids. A series of alkoxy group donors were studied and triethyl orthoacetate was found to be the best reagent as well as a solvent for the performed transformations. An important temperature effect on the reaction course was discovered.

Pyridine Derivatives-A New Class of Compounds That Are Toxic to K12, R2-R4 Strains.

A preliminary study of 2-amino-4-aryl-3,5-dicarbonitrile-6-thiopyridines as new potential antimicrobial drugs was performed. Special emphasis was placed on the selection of the structure of target pyridine derivatives with the highest biological activity against different types of Gram-stained bacteria by lipopolysaccharide (LPS). Herein, model strains K12 (without LPS in its structure) and R2-R4 (with different lengths of LPS in its structure) were used.

Wheat germ lipase: isolation, purification and applications.

In recent years, wheat germ lipase (WGL) is attracting considerable interest. To date, several WGL applications have already been described: (i) fats and oils modification; (ii) esterification reactions in organic media, accepting a wide range of acids and alcohols as substrates; (iii) the asymmetric resolution of various chiral racemic intermediates; (iv) more recently, the promiscuous activity of WGL has been shown in carbon-carbon bond formation. To date, no crystallographic structure of this enzyme has been published, which means its activity, catalytic potential and substrate scope is being assessed empirically.

δ-Lactones-A New Class of Compounds That Are Toxic to K12 and R2-R4 Strains.

Lactones are among the well-known organic substances with a specific taste and smell. They are characterized by antibacterial, antiviral, anti-inflammatory, and anti-cancer properties. In recent years, among this group of compounds, new biologically active substances have been searched by modifying the main (leading) structure with new analogs with stronger or different responses that may have a toxic effect on the cells of pathogenic bacteria and constitute an alternative to commonly used antibiotics.

Evaluation of -Diacetates as Alternative Reagents for Enzymatic Regio- and Stereoselective Acylation of Alcohols.

diacetates have been used as sustainable acyl donors for enzymatic acylation of chiral and nonchiral alcohols. Especially, it was revealed that diacetates showed higher reactivity than vinyl acetate for hydrolases that are sensitive to acetaldehyde. Under optimized conditions for enzymatic acylation, several synthetically relevant saturated and unsaturated acetates of various primary alcohols were obtained in very high yields up to 98% without / isomerization of the double bond.

1,2-Diarylethanols-A New Class of Compounds That Are Toxic to K12, R2-R4 Strains.

An initial study of 1,2-diarylethanols derivatives as new potential antibacterial drugs candidates was conducted. Particular emphasis was placed on the selection of the structure of 1,2-diarylethanols with the highest biological activity of lipopolysaccharides (LPS) in the model strains of Escherichia coli K12 (without LPS in its structure) and R2-R4 (with different lengths of LPS in its structure). In the presented studies, based on the conducted minimum inhibitory concentration (MIC) and MBC tests, it was demonstrated that the antibacterial (toxic) effect of 1,2-diarylethanols depends on their structure and the length of LPS bacteria in the membrane of specific strains.

Evaluation of thionolactones as a new type of hydrogen sulfide (HS) donors for a blood pressure regulation.

Hydrogen sulfide (HS) is a gaseous molecule that exhibits various biological effects. For example, HS has been recognized as a blood pressure-lowering agent. Presented in this report is a new modifiable platform for HS supply, its preparation and HS release kinetics from a series of structurally diversified thionolactones.