Showing papers by "Tolstikov Genrikh A published in 2004"

Design of arylimine postmetallocene catalytic systems for olefin polymerization : I. Synthesis of substituted 2-cycloalkyl-and 2,6-dicycloalkylanilines

Abstract: A convenient synthetic approach to substituted 2-cycloalkyl- and 2,6-dicycloalkylanilines, involving catalytic hydrogenation on Raney nickel in methanol of readily available o-cycloalkenylanilines prepared by reaction of cyclic alkyl halides with anilines.

Synthesis and antiviral activity of amides and conjugates of betulonic acid with amino acids

Abstract: Betulonic acid amides with aliphatic and heterocyclic amines and with L-amino acids were synthesized by the acid chloride method. Betulonic acid amide and L-methionine derivatives of betulonic acid and its 3-oxime effectively inhibit the influenza A virus. Betulonic acid octadecylamide is active against the herpes simplex Type 1 virus. The conjugate of betulonic acid 3-oxime with L-methionine is also active toward HIV-1. The tested compounds mainly show no activity toward the ECHO6 virus, which is devoid of a coat.

Synthesis and Antiviral Activity of Lupane Triterpenoids and Their Derivatives

Abstract: It was reported that derivatives of lupane triterpenoids (lupeol, betulin, betulinic acid) exhibit antiviral activity, in particular, with respect to human immunodeficiency virus (HIV) [1], herpes simplex virus (HSV), and Epstein – Barr virus (EBV) [2 – 7]. Previously, we have also studied the anti-HIV properties of betulin 3,28-di-O-nicotinate [8] and the antiviral activity of some betulin oximes [9] and 28-oxo-allobetulone [10]. In continuation of our investigations of the structure – antiviral activity relationship in the series of lupane triterpenoids, we have synthesized a series of new derivatives and studied their activity in comparison to that of the known compounds. Lupeol 3-O-nicotinate (II) was obtained with 94% yield by acylating lupeol (I) with nicotinic acid chloroanhydride in a mixture of anhydrous pyridine and tributylamine. 2-Furfurylidene methylbetulonate (IV) was synthesized via interaction of methylbetulonate (III) with furfurol in an alcohol solution of alkali (after purification by column chromatography, the product yield was 80%). The proposed structures of compounds II and IV were confirmed by NMR data (see experimental part below). N-formylamine (V) was obtained with a 62% yield using the Leuckart reaction between methylbetulonate (III) and formamide in formic acid. The C NMR spectrum of this compound displays a shift of the signal from the C3 nuclei toward stronger field ( = 56.3 ppm) and reveals a signal due to C1 atom at = 164.1 ppm. In the H NMR spectra, the signals from ptotons of the formyl group is manifested by a singlet at = 8.15 ppm and the NH proton, by a broad signal at = 8.00 ppm.

New Bis(arylimino)pyridyl Complexes as Components of Catalysts for Ethylene Polymerization

Abstract: A new series of 2,6-bis(arylimino)pyridineiron(II) complexes with cycloaliphatic (cyclopentyl, cyclohexyl, cyclooctyl, and cyclododecyl) substituents in the ortho position of the aryl ring are synthesized and studied as components for ethylene polymerization catalysts. Methylaluminoxane is used as an activator for the complexes. The resulting catalytic systems are more active in polymerization at elevated temperatures (60–80°C) than previously described systems based on substituted 2,6-bis(arylimino)pyridines. The influence of the number of CH2 groups in a cycloaliphatic substituent on the efficiency of the catalytic system is studied. Polymers formed are characterized by an increased molecular weight, high density, and high crystallinity.

Synthesis and pharmacological activity of acylated betulonic acid oxides and 28-oxo-allobetulone

Abstract: In recent years, the chemical transformations and biological activity of triterpenoids of the lupane group have received much attention. It was found that betulin acylates possess antitumor properties [1], while lupeol esters with palmitic and linolic acids produce antiarrhythmic action [2]. The most promising inhibitors of HIV replication include 3-O-(3,3-dimethylsuccinate) of betulinic acid and 3-O(3,3-dimethylsuccinate)-28-O-(2,2-dimethylsuccinate) of betulin [3]. Recently, Kashiwada et al. [4] reported on the synthesis of derivatives of 3-alkylamino-3-deoxo-betulinic acid possessing anti-HIV-1 properties [4]. Another promising compound is betulin 3,28-di-O-nicotinate, which shows hepatoprotector, antiulcer, antiinflammatory, wound-healing, anti-HIV, and immunomodulant activity [5]. An analysis of published data suggests that the class of lupane triterpenoids and related compounds containing acyl groups is a promising source of new biologically active substances. Below we report on the first synthesis of acylated oximes based on betulonic acid (Ia), its methyl ester (IIa), and 28-oxo-allobetulone (IIIa). In the first step, boiling 3-oxo-triterpenoids (Ia, IIa, IIIa) with hydroxylamine hydrochloride in anhydrous pyridine led to a quantitative yield of the corresponding 3-oximes (Ib, IIb, IIIb). By acylating these compounds in anhydrous benzene with excess acetic, succinic, and phthalic anhydrides at room temperature in the presence of triethylamine, we obtained acylated oximes (Ic – Ie, IIc – IIe, IIIc – IIIe) with a yield of 64 – 78% after purification of the products by column chromatography (Table 1).

Selective oxidation of triterpene alcohols by sodium hypochlorite

Abstract: 3-Oxo-triterpenoids were prepared by oxidation of the methyl esters of glycyrrhetic acid, allobetulin, and 20-oxo-29-nor-betulin with sodium hypochlorite in acetic acid or methylene chloride under phase-transfer conditions.

Design of Schiff base-like postmetallocene catalytic systems for polymerization of olefins: II. Synthesis of 2,6-bis(aryliminoalkyl)pyridines with cycloalkyl substituents

Abstract: Reactions of substituted cycloalkylanilines with 2,6-diacetylpyridine in methanol in the presence of formic acid afforded a wide series of the corresponding bis(cycloalkylaryliminoalkyl)pyridines which can be used as ligands for the preparation of iron and cobalt complexes.

Kinetics of oxidation of an arabinogalactan from larch (Larix sibirica L.) in an aqueous medium in the presence of hydrogen peroxide

Abstract: The oxidation of an arabinogalactan in an aqueous medium under the action of hydrogen peroxide and dioxygen is accompanied by accumulation of carbonyl and carboxy groups in the oxidized polysaccharide macromolecules and derived oligomers. The addition of iron sulfate accelerates the radical oxidation of the biopolymer, while the addition of phenol inhibits the oxidation. The influence of the temperature and the initial H2O2 and arabinogalactan concentrations on the kinetics of the initial oxidation stage of the natural polysaccharide was studied.

Synthetic Transformations of Higher Terpenoids: XI. Synthesis of A-Nor-5bH-19b,28-epoxy-18a-olean-3-one Derivatives

Abstract: Starting with allobetulin triterpenoid A-nor-derivatives with a cis-junction of A/B rings were prepared for the first time.

[Synthesis and immunomodulating activity of new diglycopeptides of of glycyrrhizinic acid and it's 30-methyl ester].

Abstract: New amino acid derivatives of glycyrrhizic acid and its methyl ester were selectively synthesized using active N-succinimide esters. The compounds with residues of glycine ethyl ester and alanine methyl and butyl esters increased the level of agglutinins and hemolysins in blood serum of mice two- to threefold in comparison with the control upon parenteral administration at a dose of 2 mg/kg for 14 days.

Synthesis and Immunostimulating Activity of Cysteine-Containing Derivatives of Glycyrrhizic Acid

Abstract: New cysteine-containing derivatives of glycyrrhizic acid were synthesized by its coupling with Cys(Bzl) esters or the Cys(Bzl)-Val-OBu t dipeptide by the active ester method (DCC/HOSu) or by Woodward's reagent K. The derivatives with Cys(Bzl) and Cys(Bzl)-Val residues attached to the carbohydrate part of the molecule stimulated the primary immune response and the reaction of delayed-Type hypersensitivity in mice at a dose of 2 mg/kg.

Synthesis of 4,5-seco-derivatives of allobetulin

Abstract: 4,5-Seco-19β,28-epoxy-18α-olean-3,5-dione wasprepared by ozonation of 19β,28-epoxy-18α-olean-3(5)-ene. The structures of the synthesized compounds were confirmed using spectral data.

[The synthesis and antiviral activity of glycyrrhizic acid conjugates with alpha-D-glucosamine and some glycosylamines].

Abstract: Glycyrrhizic acid and its 30-methyl ester were conjugated with 2-amino-1,3,4,6-tetra-O-acetyl-2-deoxy-alpha-D-glucopyranose, 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl amine, 2,3,4-tri-O-acetyl-apha-L-arabinopyranosyl amine, 2-acetamido-2-deoxy-beta-D-glucopyranosyl amine, and beta-D-galactopyranosyl amine using N,N'-dicyclohexylcarbodiimide and its mixtures with N-hydroxybenzotriazole. Structures of the conjugates were confirmed by IR, UV, 1H, and 13C NMR spectroscopy. The glycoconjugate with the residues of 2-acetamido-2-deoxy-beta-D-glucopyranosyl amine in the carbohydrate part of its molecule exhibited antiviral activity (ID50 4 microg/ml) toward the herpes simplex type 1 virus (HSV-1) in the VERO cell culture. Two compounds demonstrated anti-HIV-1 activity (50-70% inhibition of p24) in a culture of MT-4 cells at concentrations of 0.5-20 microg/ml. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 3; see also http://www.maik.ru.

Synthesis of 1,2,3-thiadiazolo terpenoids on the basis of cyclopentanonopimaric and betulonic acids

Abstract: The Hurd-Mori reaction with derivatives of cyclopentanonopimaric and betulonic acids afforded mostly the corresponding 1,2,3-thiadiazoles and small amounts of thioketone oxides.

Diels–Alder Reactions with Cyclic Sulfones: VII. Synthesis of 1-Benzothiophene 1,1-Dioxide Derivatives

Abstract: 5-Arylmethylene-2,2-dimethyl-1,3-dioxane-4,6-diones reacted with 5-isopropenyl-2,3-dihydrothio-phene 1,1-dioxide to give the corresponding ortho-addition products, 5-aryl-2',2',7-trimethyl-3,3a,5,6-tetra-hydro-2H-spiro[1-benzothiophene-4,5'-[1,3]dioxane]-4',6'-dione 1,1-dioxides. Their aminolysis resulted in opening of the 1,3-dioxane ring and formation of 4-carbamoyl-7-methyl-2,3,3a,4,5,6-hexahydro-1-benzo-thiophene-4-carboxylic acid 1,1-dioxide whose structure was determined by X-ray analysis. Reactions of the spiro adducts with amines and hydrazine hydrate afforded the corresponding mono- or dicarboxylic acid monoamides (hydrazide).

Neurotropic activity of lambertianic acid adducts with N-substituted maleinimides

Abstract: Terpenoids of the labdane series have been extensively studied as potential drugs. In particular, forskolin and a derivative of this labdanoid were used for the treatment of glaucoma [1]. It was also reported that labdanoids showed fungistatic and antibacterial activity [2, 3], produced a cytostatic effect [4], inhibited biosynthesis of cholesterol [5], suppressed thrombocyte aggregation [6], and exhibited antilipoxygenase action [7]. Recently, we have established [8] that lambertianic acid (I) – a readily available labdanoid contained in siberian cedar (Pinus sibirica R. Mayr.) – is a potential neurotropic agent [9]. Synthetic nitrogen-containing derivatives of lambertianic acid exhibit pronounced nootropic properties [10 – 12].

Novel synthesis of (4R)-4-methylpentanolide from (L)-(−)-menthol

Abstract: A novel synthesis of the promising optically pure chiral (4R)-4-methylpentanolide that is based on several regiospecific oxidative transformations of (4R)-2,4-dimethyl-1-(1-methylethyl)-1-cyclohexene, the product of addition of (−)-menthone and methylmagnesium iodide followed by acid dehydration, was proposed.

Xanthones from Halenia corniculata. Synthesis and cholagogic action of certain derivatives

Abstract: Xanthones containing acetoxy, allyloxy, and aminohydroxyalkyloxy substituents at the C-1 position that are of interest as potential biologically active agents were prepared. The cholegogic action of 1-hydroxy-, 1-acetoxy-, and 1-allyloxy-substituted xanthones was investigated.

Effect of natural and artificial defoliation on concentration and composition of extractive substances in leaves of birch (Betula pendula Roth.): methods of analysis and results.

Abstract: Allelochemicals, or secondary metabolites (e.g., phenolic compounds), play an important role in the system of regulation of plant growth and development [1]. Secondary metabolites are also believed to contribute to active protection of plants against insects [2]. Defoliation of fodder plants increases their resistance to insects, thereby causing a decrease in the viability of phyllophages and an increase in their sensitivity to pathogens [2–6]. Therefore, studies of plant response to defoliationinducing insects are of particular interest. Although there is limited literature on this subject, both the upgrade to the methodological approaches to analyze plant response to defoliation and studies of possible role of various allelochemicals (other than phenolic compounds) in plant resistance are of considerable interest. The goal of this work was to develop an effective method of analysis and to use this method for assaying extractive substances in leaves of weeping birch ( Betula pendula Roth.), the main food of gipsy moth ( Lymantria dispar L.) in broad-leaved forests of Western Siberia. P r e p a r a t i o n o f m a t e r i a l . Ten-year-old birch leaves were collected in natural birch forests during periods of mass-scale reproduction of gipsy moth in these forests (Novosibirsk oblast, seasons 1999–2001). Leaves of experimental trees were collected 30 days and one year after natural (eating by gipsy moth) or artificial (artificial defoliation) damage had been inflicted on the trees (the volume of damage was 75%). Leaves of control trees were collected during the same period of time. Extractive substances were isolated from leave samples dried at room temperature. G e n e r a l s c h e m e o f i s o l a t i o n o f e x t r a c t i v e s u b s t a n c e s . A 40-g sample of airdried leaves cut into small pieces was subjected to triple extraction with 150 ml of diethyl ether at 20 ° C. The resulting extract was incubated in the dark for 2 days after each extraction. The extracts were pooled, washed with water, and dried with magnesium sulfate. The solvent was evaporated until dry. The dry residual was dissolved by heating in 10 ml of methanol and cooled. The wax fraction precipitate (extract-1) was separated and analyzed. Methanol solution was mixed with the solution containing 0.5 g KOH in 40 ml of methanol and boiled for 2 h. The resulting hydrolyzate was diluted with water (4 ml) and extracted four times with 100 ml of ether (extract-2). Water layer was neutralized and extracted once more with ether (extract-3). The plant material extracted with ether was placed in 50 ml of 70% aqueous methanol, incubated for 2 days at 20 ° C, evaporated to half-volume (residual volume, 25 ml), extracted with methyl-tert-butyl ether, dried, and evaporated (extract-4). Concentrated solution of HCl (1.5 ml) was added to the water layer, boiled for 30 min, cooled, and neutralized with soda solution. Cooled material was extracted with methylene chloride. The resulting organic layer was dried with magnesium sulfate and evaporated (extract-5).

[The anti-HIV activity of glycyrrhizic acid penta-O-nicotinate].

Abstract: The anti-HIV activity of niglizin (penta-O-nicotinate of glycyrrhizic acid) and of its combinations was studied in the culture of infected MT-4 cells and in respect to the recombinant reverse HIV-1 transcriptase. Niglizin was shown to suppress effectively the HIV replication and to be a noncompetitive inhibitor of reverse transcriptase. Research of a combined anti-HIV action of niglizin and of azidothimidine (AZT) demonstrated that the preparations, when used at ratios of 1:20, 1:50, 1:200 and 1:2000, suppressed the synergetic effect both in the cell culture and in the recombinant reverse HIV transcriptase. A study of the antiviral activity of niglizin and of its joint use with AZT in respect to the AZT-resistant HIV-1 mutant showed niglizin to be more effective (ID50 = 0.134 microM) versus the "wild" strain. (ID50 = 9.64 micriM); whereas, its combined use AZT:niglizin = 1:100 displayed synergism (FIC = 0.553). The efficiency of the combined AZT/niglizin anti-HIV effect both in respect to the "wild" strain and to the AZT-resistant mutant confirms that such combinations are promising for the treatment of HIV infection.

Synthesis of the lupinine ester of betulonic acid

Abstract: The lupinine ester and 3-oxime of betulonic acid were prepared for the first time.

Functionalization of the Allyl Fragment in (+)-δ-Cadinol

Abstract: Epoxidation, bromination, and iodination of the double bond in (+)-δ-cadinol under various conditions are accompanied by formation of 1,4- or 1,5-epoxy derivatives. By contrast, vicinal hydroxylation gives rise to “normal” products. Intramolecular cyclization of the resulting vicinal diols was studied.

New approach to the synthesis of (R)-3-methyl-γ-butyrolactone

Abstract: Optically active pure (R)-3-methyl-γ-butyrolactone was synthesized from (R)-4-menthenone.

(R)-4-Menthenone in the Synthesis of Optically Pure Sex Pheromone of the Peach Leafminer Moth (Lyonetia clerkella).

Abstract: The synthesis of (14S)-methyloctadec-1-ene, sex pheromone of the peach leafminer moth (Lyonetia clerkella), is described to demonstrate a new potential of the synthetic use of (R)-4-menthenone.

A new group of highly active analgesic of the morphinan family.

Abstract: Synthetic transformations of the alkaloid thebaine are widely used in opioid drug production [1]. In the past two decades, much attention has been given to thebaine derivatives containing added carbonyl groups and heterocycles [2–9]. Of particular interest are the thebaine derivatives with N-containing heterocycles annealed to the C ring, of which some are selective ligands for δ [5, 6] and χ [7–9] opioid receptors. To synthesize 7,8-pirrolidino-6,14-endoethenotetrahydrothebaine derivatives, N-substituted maleimides were allowed to react with thebaine in diene reactions, and the adducts were subjected to further transformations. We tested more than 20 compounds of this type; the results allow us to speak of a new group of highly active analgesics. Three compounds with the following common formula are the most promising in this group:

Synthesis of Phenyl-2,3-oxazine Derivatives of Chrysenequinonecarboxylic Acid

Abstract: A mixture of isomeric phenyloxazines (2, 3) in a 5:4 ratio was synthesized via a [4 + 2] addition reaction of a heterocyclic diene-precursor prepared from bromoacetophenone oxime and the methyl ester of chrysenequinonecarboxylic acid (1). The structures of the synthesized compounds were confirmed using spectral methods.

Synthesis of 30-amino derivatives of 3,28-di-O-acetylbetulin

Abstract: 30-Amino derivatives of the lupane group were prepared by reaction of 3,28-di-O-acetyl-30-bromolup- 20(29)-ene with L-valine methyl ester and aliphatic amines.

New Synthesis of 9-Methanesulfonyl-1,2,3,9a-tetrahydro- and 1,2,3,4-tetrahydrocarbazoles from N-Methanesulfonyl-2-(cyclohex-1-enyl)aniline.

Abstract: The reaction of N-methanesulfonyl-2-(cyclohex-1-en-1-yl)aniline with Br2 in the presence of NaHCO3 in MeCN results in N-methanesulfonyl-2-(6-bromocyclohex-1-en-1-yl)aniline, which was cyclised to 9-methanesulfonyl-1,2,3,4-tetrahydrocarbazole, and the effect of NH3 leads to 9-methanesulfonyl-1,2,3,9a-tetrahydrocarbazole. The reaction of the latter with molecular bromine in the presence of pyridine results in 1-(9-methanesulfonyl-1,2,3,4-tetrahydro-4-carbazolyl)pyridinium bromide in a good yield.