Showing papers by "Valery M. Dembitsky published in 2017"

Pharmacological and Predicted Activities of Natural Azo Compounds.

Abstract: This paper describes research on natural azo compounds isolated from fungi, plant, bacteria, and invertebrates. More than 120 biologically active diazene containing alkaloids demonstrate confirmed pharmacological activity, including antitumor, antimicrobial, and antibacterial effects. The structures, origin, and biological activities of azo compounds are reviewed. Utilizing the computer program PASS, some structure–activity relationship new activities are also predicted, pointing toward possible new applications of these compounds. This article emphasizes the role of natural azo compounds as an important source of drug prototypes and leads for drug discovery.

Pharmacological Activities of Epithio Steroids

Abstract: The present review describes biological activities of semi- and synthetic epithio steroids. About fifty biologically active compounds have shown confirmed antitumor, immunosuppressant, or aromatase inhibition and other activities. More than a quarter of all studied steroids belong to the group of anabolic steroids, and they showed many new and additional activities. Epithio steroids possess mainly cytotoxic activities, although the predicted biological activity showed a broad spectrum of activities. As we found, the position of the epithio group in the core of steroids can significantly change the activity of steroids. The structures, as well as reported and predicted activities of a selection of epithio steroids, are reported. With the computer program PASS based on structure–activity relationships (SAR), some additional activities are also predicted, which point toward new possible applications of these lipids. This review emphasizes the role of epithio steroids as an important source of leads for drug discovery, and they are of great interest to chemists, physicians, biologists, pharmacologists and the pharmaceutical industry.

Boranes in Organic Chemistry 1. α-Carbonylalkyl- and β-Oxyalkylboranes in Organic Synthesis

Abstract: This review is devoted to the synthesis of a-carbonylalkyl- and β-hydroxy-alkyl boranes and their use in organic synthesis. a-Carbonyl-alkylboranes include several heteroatomic compounds, in particular, [1.2.3]-diazaborinines, uracyl boronic acids, and [1.2.3.4]-diaza-diboretes. The latter type has been obtained by the ketene aminoborations. The reactions of halogenboranes with diazoesters and sulfur ylides resulting in formation of a-carbonyl alkylborates containing diazofunction or ylide structural fragment are described. Amino and halogen boration of acetylenic acid esters was also used for the synthesis of a-carbonyl alkyl boranes. Reactions involving Cr-carbene complexes and acetylenic borone esters were presented for the synthesis of naphthoquinone boronic acids. The formation of amidoboranes by boration of dichloroacetanilides was remined. Boration of 4,8-dimethoxy-2-quinolone with trimethylborates leading to 2-quinolone-3-boronic acid was described. The common synthetic method to a-carbonyl alkyl boranes based on the hydroboration of acrylic acid derivatives was discussed. The results of enhydrazones hydroboration, leading to stable cyclic complexes have been mentioned. The interaction of a-bromoketones with trialkyl or dialkylboranes represents as a general synthetic method to a-carbonyl alkyl boranes. Synthetic approaches to â-hydroxy alkyl boranes are performed. The wide spread hydroboration of vinyl and allyl esters received a well-described attention. The hydroboration of cyclanone enol acetates, 3-keto- and 17-keto-steroids and cyclic allyl alcohol acetates was discussed. The results of aliphatic and alicyclic vinyl esters (including dihydrofuran derivatives) boralylation leading to β-hydroxy alkyl boranes have been envisaged. The synthesis of optically active β-hydroxy alkyl boranes using chiral borane hydrides was discussed. The heterocyclic boran dihydrides are obtained by the hydroboration of dihydropyranes, chromenes and flavenes. Borosilylation of allyl allenylic esters was also been envisaged. The synthetic scheme to optically active boranes and further optically active alcohols were presented. The problems of selectivity regularities in hydroboration reaction by intermolecular complex formations have been discussed.

Halogenated (Cl, Br and I) marine steroids and their biological activities: A brief review

Abstract: The present review describes the biological activities of natural halogenated (Cl, Br and I) marine steroids. More than twenty biologically active steroids have shown confirmed anti-tumour, antibacterial, antiviral and other activities. The structures and reported and predicted activities of natural halogenated steroids are available. With the computer programme PASS and based on structure–activity relationships (SAR), some additional activities are also predicted, which point towards new possible applications of these lipids. This review emphasizes the role of natural halogenated steroids as an important source and potential leads for drug discovery and they are of great interest to chemists, physicians, biologists, pharmacologists and the pharmaceutical industry.

The Use Haloperoxidases in Organic Synthesis: Selected Reactions of Oxidation, Epoxydation and Sulfoxidation

Abstract: Haloperoxidases are ubiquitous metalloenzymes that catalyse a variety of enantioselective oxygen-transfer reactions with hydrogen peroxide or alkylperoxides. Haloperoxidases are enzymes which catalyze the reaction of oxidation, epoxidation and sulfoxidation by hydrogen peroxide. These enzymes usually contain the FeHeme moiety or vanadium as an essential constituent at their active site, however, a few haloperoxidases which lack a metal cofactor are known. This review will examine the reactivity of the different haloperoxidases, particularly the mechanism of oxidation by hydrogen peroxide, and the mechanism of oxidation and sulfoxidation, including the newly reported regioselectivity and enantioselectivity of the haloperoxidases. The structure of chloroperoxidase, the vanadium active site and the role of critical amino acid side chains for catalysis and functional biomimetic systems, with specific relevance to the mechanism of the haloperoxidase enzymes. Advances have recently been made in using them to prepare, under controlled conditions, chiral organic molecules that are valuable for the synthesis of a wide range of useful compounds. The application of biocatalytic methods in asymmetric organic synthesis is of great interest as an alternative to chemical procedures employing chiral auxiliaries. Asymmetric oxidation of prochiral sulfides to yield optically active sulfoxides has been performed by many different techniques yielding varying enantiomeric excess values. Oxygenated metabolites are compounds that are commonly found in nature and they are produced by many different organisms. The oxygen atom is incorporated into organic compounds by enzyme-catalyzed reactions with oxygen ions as the oxygen source. For over 40 years haloperoxidases were thought to be responsible for the incorporation of mainly halogen atoms into organic molecules. However, haloperoxidases lack substrate specificity and regioselectivity, and the connection of haloperoxidases with the in vivo formation of oxygenated as well as halometabolites has been demonstrated. Recently, molecular genetic investigations showed that, at least in bacteria, fungi, and other organisms a different class of halogenases is involved in halo- and oxygenated metabolite formation. These halogenases were found to require FADH2, which can be produced from FAD and NADH by unspecific flavin reductases. The FADH 2 -dependent halogenases and haloperoxidases show substrate specificity and regioselectivity, and their genes have been detected in many halometabolite-producing organisms, suggesting that this type of halogenating enzymes constitutes the major source for halo- and oxygenated metabolite formation in bacteria and also in other organisms. Distribution of haloperoxidases in nature also is demonstrated in this brief review.

Boranes in Organic Chemistry 2. ОІ-Aminoalkyl- and ОІ-sulfanylalkylboranes in organic synthesis

Abstract: Problems on using of ОІ-aminoalkyl- and ОІ-sulfanylalkylboranes in organic synthesis are considered in this review. The synthesis of boron containing a-aminoacids by Curtius rearrangement draws attention. The use of ОІ-aminoalkylboranes available by enamine hydroboration are described. Examples of enamine desamination with the formation of alkenes, aminoalcohols and their transformations into allylic alcohol are presented. These conversions have been carried out on steroids and nitrogen containing heterocyclic compounds. The dihydroboration of N-vinyl-carbamate and N-vinyl-urea have been described. Examples using nitrogen and oxygen containing boron derivatives for introduction of boron functions were presented. The route to borylhydrazones by hydroboration of enehydrazones was envisaged. The possibility of trialkylamine hydroboration was shown on indole alkaloids and 11-azatricyclo-[6.2.11,802,7]2,4,6,9-undecatetraene examples. The synthesis of ОІ-sulfanyl-alkylboranes by various routes was described. The synthesis of boronic thioaminoacids was carried out by free radical thiilation of dialkyl-vinylboronates. Ethoxyacetylene has been shown smoothly added 1-ethylthioboracyclopentane. Derivatives of 1,4-thiaborinane were readily obtained by divinylboronate hydroboration. Dialkylvinylboronates react with mercaptoethanol with the formation of 1,5,2-oxathioborepane derivatives. Stereochemistry of thiavinyl esters hydroboration leading to stereoisomeric ОІ-sulfanylalkylboranes are discussed. Examples of radical thiilation of various structural types vinylboronates were presented. In particular, 1,3,2-dioxaborinanes and 1,3,2-dioxaborolanes, containing by boron atom vinyl-, propenyl-, isopropenylor isopropylidene substituents have been used. Thiilation has been achieved by use of alkylmercaptanes, as well as mercaptamine derivatives. Alkylmercaptanes were able to replace the bromine substituent in tris-(2-bromoctyl)-borane. Dialkylvinylborates have been added hydrosulfite with the formation of 2-boronoethane sulfuric acids. A lot of examples of radical thiilation of vinylboronic acid dialkyl esters with mercaptoacids are presented. Under the azaisobutyric acid dinitryle conditions thioglycolic, ОІ-mercaptopropionic, 2-mercaptoamberic acids and their esters as well as cysteine were added. Vinyl-, propenyl- and isopropenyldioxaborolanes were also participated in the thiilation with the formation of acetic, propionic or amberic acid thioethanoboronates. The high reactivity of B,B,B-trivinyl-N,N,N-triphenylborazine in the reaction with thiophenol, leading to B-tris-(phenylmercaptoethyl)-N-phenylborazine was shown. The problems of asymmetric hydroboration leading to chiral ОІ-sulfanylalkylboranes were discussed briefly. In particular, an example, including dihydro-thiophene hydroboration, leading to (+)-R-thiofan-3-yl-diisopinocamphenylborane, and the interaction with acetaldehyde with the formation of (+)-R-3-thiophanyl-diethoxyborane was implemented. The reaction with 3,4-dihydrothiapyrane proceeds analogously. A synthetic route to sulfono-norbornen-boronic acid esters by Diels-Alder reaction of cyclopentadiene with arylsulfanyl-vinylboronic acid esters has been discussed.

Synthetic steroids containing a tertiary butyl group and their biological activities

Abstract: The present review article describes biological activities of synthetic steroids containing a tertiary butyl group. More than 25 biological active steroids have shown confirmed antitumor, antiviral, or apoptosis, and other activities. The structures, reported and predicted activities of a selection of describes steroids are reported. With the computer program PASS based on structure–activity relationships (SAR) some additional activities are also predicted, which point toward new possible applications of these lipids. This article emphasizes the role of steroids containing a tertiary butyl group as an important source of leads for drug discovery.

Natural hydroperoxides as potential therapeutic agents

Abstract: Peroxy-containing metabolitesare an interesting group amongbiological active natural compounds. These metabolites contain a peroxide group (-O-O-) in which each oxygen atom is bonded to the other oxygen an to another atom. β-Oxygen in hydroperoxide group is considered as moreactive.Present review describes research on more than 100 natural hydroperoxidesand rare acyclic peroxides isolated from plants, algae, and fungi. Intensive searches for new classes of biologicallyactive metabolites produced by terrestrial and marine origin have resulted in the discovery of dozens of compounds possessing high antimalarial,antibacterial, cytotoxic, and other pharmacological activitiesas an important source of leads for drug discovery. Received date: 11-08-2015; Accepted date: 19-09-2015; Published date: 21-09-2015