R. L. Antipin

Synthesis, SAR and molecular docking study of novel non-β-lactam inhibitors of TEM type β-lactamase

The novel classes of acylated phenoxyanilide and thiourea compounds were investigated for their ability to inhibit TEM type β-lactamase enzyme. Two compounds 4g and 5c reveal the inhibition potency in micromolar range and show their action by non-covalent binding in the vicinity of the TEM-171 active site. The structure activity relationship around carbon chain length and different substituents in ortho- and para-positions of acylated phenoxyanilide as well as molecular modelling study has been performed.

Novel Chromogenic Substrate for Bacterial β-Lactamases Based on Cephalosporin Modified with an Epoxy Group

Beta-lactamases are the key enzymes involved in resistance to beta-lactam antibiotics in pathogenic bacteria causing infectious diseases. The search for new inhibitors and the study of the resistance mechanisms require the production of chromogenic substrates for beta-lactamases. A novel cephalosporin derivative with an epoxy functional group named CMPD1 is synthesized. It is shown to be a substrate for TEM type beta-lactamases, which is hydrolyzed to form a colored product. The hydrolysis product has an optical absorption maximum at 450 nm. The difference in the absorption maxima of the substrate and the product is 95 nm, and, therefore, CMPD1 exceeds the previously described substrates, according to this parameter. It has been found that the CMPD1 compound is hydrolyzed only by the TEM type beta-lactamases that lack mutations in the active site. This can be used to study the mechanisms of the catalytic effect of beta-lactamases.

7-Azabicyclo[2.2.1]heptadienes in electrophilic chalcogenation reactions

Reactions of electrophilic chalcogenation (sulfenylation and selenenylation) of 7-azabicyclo[2.2.1]heptadiene derivatives with electron-withdrawing substituents at the nitrogen atom and the double bond were found to proceed trans-stereospecifically with the formation of 1,2-addition products, resulting from the exo-attack by the electrophile. In the case of 2-tosyl-7-azanorbornadiene, the reaction is regiospecific: the electrophilic species exclusively adds to the carbon atom at position 6. A comparative analysis of the behavior of dimethyl bicyclo-[2.2.1]heptadiene-2,3-dicarboxylate and its 7-aza analogs in the AdE reactions was carried out.

New sulfanyl- and selanyl-substituted Schiff bases derived from 2-chalcogenoalkylamines and aromatic aldehydes. Synthesis and complex formation reactions

A number of β-phenyl(or benzyl)selanyl- and β-phenylsulfanyl-substituted imines possessing an additional donor nitrogen, oxygen, or sulfur atom were synthesized by reaction of 2-phenylsulfanylethanamine, 2-phenylsulfanylcyclohexanamine, 2-phenylselanylcyclohexanamine, and 2-benzylselanylaniline with salicylaldehyde, 2-pyridinecarbaldehyde, or 2-tert-butylsulfanylbenzaldehyde. The resulting Schiff bases were tested as ligands in the complex formation with nickel(II) and copper(II), and mononuclear (L-H)MCl or LMCl2 coordination compounds were isolated (L = sulfur- or selenium-containing imine). The redox properties of the selenium-containing ligands and complexes were studied by cyclic voltammetry. The complexes were found to undergo reduction of the metal ion in two one-electron steps. The reduction is reversible for copper complexes and irreversible for nickel complexes.

Synthesis and coordinating properties of 5-phenyl- and 5-pyridylmethylidene-substituted 2-selenohydantoines and 2-selenoimidazol-4-ones

Abstract2-Selenoimidazolidin-4-ones and 2-selenoimidazol-4-ones containing phenylor pyridylmethylidene substituent at position 5 were synthesized. The structure of 3-benzyl-2-selenohydantoine was confirmed by X-ray crystallography. A series of 2-(methylseleno)imidazol-4-ones was obtained by alkylation of 3,5-disubstituted selenohydantoines with methyl iodide. The synthesized selenohydantoines and 3-benzyl-5-pyridylmethylidene-2-(methylseleno)imidazol-4-ones were examined in the complexation reactions with CoCl2, NiCl2, CuCl2, and CuI(CH3CN)4ClO4; electrochemical investigations showed that reduced forms of the copper-containing complexes were stable

Reaction of [3.3.1]propellanes with diaryl diselenides

While searching for methods of synthesis of new selenium-containing adamantane derivatives, we used as initial compounds two representatives of [3.3.1]propellanes, 1,3-dehydroadamantane (Ia) and 5,7-dimethyl-1,3-dehydroadamantane (Ib), which are known to be highly reactive in radical processes. Reactions of diaryl diselenides with propellanes were studied previously only with [1.1.1]propellane as an example [3].

Reactions of areneselenenamides with alkenes in the presence of phosphorus(V) and sulfur(IV) oxyhalides. New synthesis of β-haloalkyl selenides

A new procedure was proposed for activation of areneselenenamides with phosphorus(V) and sulfur(IV) oxyhalides. According to the 1H, 13C, and 31P NMR data, areneselenenamide reacts with phosphorus oxyhalide to form intermediate adduct in which the phosphorus atom is coordinated at the selenium. Areneselenenamides activated by phosphorus(V) oxyhalides react with alkenes (norbornene and norbornadiene) with high trans-stereoselectivity. Their reactions with terminal olefins are regioselective, and they lead to preferential formation of the corresponding Markovnikov adducts.

Electrophilic addition to norbornene derivatives containing CF3 and NO2 groups

Electrophilic sulfenylation, selenenation, and halogenation of bicyclo[2.2.1]heptenes containing CF3 or NO2 group in position endo-5 were studied. The sulfenylation and selenenation were accomplished by arylsulfene- and arylselenenamides activated by POHal3 (Hal = Br, Cl), and iodination was performed by KICl2. The reactions are regiospecific and involve an exo-attack of the electrophilic fragment (arylthio or arylseleno group or iodine) on the C=C bond atom located closer to the CF3 or NO2 group.

Halosulfenylation of Conjugated Dienes with Arylsulfenamides in the Presence of Phosphorus Oxyhalides

Electrophilic sulfenylation of cyclic and open-chain conjugated dienes effected by a system arylsulfenamide-phosphorus oxyhalide was investigated. The initially formed adducts of 1,2-halosulfenylation in the course of the reaction and also at storage and chromatograqphic purification on silica gel undergo quantitative isomerization into a mixture of stereoisomeric products of 1,4-addition. The effect of halogen nature and the character of substituents in the benzene ring of arenesulfenamide on the addition rate of sulfenamides activated by phosphorus oxyhalides to open-chain and cyclic conjugated dienes and isomerization rate of the arising 1,2-adducts was examined.