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New potentially biologically active sulfonamide derivatives of pentacyclic lupane-type triterpenoids, the sulfonamide group of which was bonded to C-17 of the triterpene skeleton through an amidoethane spacer, were synthesized via conjugation of 2-aminoethanesulfonamides to betulinic and betulonic acids in the presence of Mukaiyama reagent (2-bromo-1-methylpyridinium iodide).

Vinylation by acetylene of lupane-type pentacyclic triterpene C-28- and C-3β-alcohols and C-20-oximes in superbase solutions synthesized the corresponding C-28- and C-3β-O-vinyl ethers and C-20-O-vinyloximes. The reaction of 3β,28-dimethoxy-29-norlupan-20-one with acetylene in superbase KOH–DMSO produced a derivative with an N-vinylpyrrole ring in the C-19 side chain.

Methyl (Z)-3-[(2R,3R,4S,5S)-5-(2-methoxy-2-oxoethyl)-3,4-(isopropylidenedioxy)tetrahydrofuran-2-yl]-prop-2-enoate was synthesized, and its intramolecular carbocyclization was studied. This reaction proceeds smoothly and quickly under the action of t-BuOK in THF, leading to three cycles with the methoxy and methoxycarbonylmethyl side substituents trans to each other. A stepwise route for the formation of methyl (1R,2R,6S,7R,8R,9R)-9-(2-methoxy-2-oxoethyl)-4,4-dimethyl-3,5,10-trioxatricyclo[5,2,1,02,6]decane-8-carboxylate and methyl (1R,2R,6S,7R,8S,9S)-9-(2-methoxy-2-oxoethyl)-4,4-dimethyl-3.5,10-trioxatricyclo-[5,2,1,02,6]decane-8-carboxylate with the trans orientation of the side substituents is proposed. The observed stereochemical result of the reaction is interpreted in terms of epimerization in the C1 and C4 centers of methyl (Z)-3-[(2R,3R,4S,5S)-5-(2-methoxy-2-oxoethyl)-3,4-(isopropylidenedioxy)-tetrahydrofuran-2-yl]prop-2-enoate, which ultimately leads to the cyclized β,β’-cis diastereomer of methyl (Z)-3-[(2R,3R,4S,5S)-5-(2-methoxy-2-oxoethyl)-3,4-(isopropylidenedioxy)-tetrahydrofuran-2-yl]prop-2-enoate and the corresponding α,α’-cis diastereomer, a precursor of methyl (1R,2R,6S,7R,8S,9S)-9-(2-methoxy-2-oxoethyl)-4,4-dimethyl-3,5,10-trioxatricyclo[5,2,1,02,6]decane-8-carboxylate.

A betulin derivative with an (imidazolium)butane-1-sulfonate fragment was synthesized and promoted proliferation in vitro of HEK293 and human T-lymphocyte cells, suggesting that this compound had immunostimulant properties.

New potentially biologically active conjugates of betulin and its 3β-O-acetate with 2-aminoethanesulfonic acid (taurine) linked through succinic or maleic acid were synthesized.

Conjugates of betulin and betulinic and betulonic acids with 2-aminoethane- and N-methyl-2-aminoethanesulfonic acids were synthesized for the first time and were interesting as potential biologically active compounds. Experiments in vitro in MDCK cell culture using the MTT assay found that betulin and betulinic-acid derivatives with aminoethanesulfonic acid bound to triterpene C-3 or C-28 through an ester linker were less toxic than the native compounds.

Platinum(II) and platinum(IV) chloro complexes with (RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1Н-1,2,4-triazol-1-ylmethyl)pentan-3-ol (L), namely, cis-[PtCl2L2], trans-[PtCl2L2], and trans-[PtCl4L2], were synthesized. The structures of their coordination cores and the coordination mode of the reagent to the metal ions via the N(4) atom of the triazole ring were determined by electronic, IR, and NMR 1H and 13C spectroscopy. The ratio between treo and erythro diastereomers and the conformation of reagent L in the complexes were established from the complete assignment of signals in their NMR spectra.

Methods for preparing sulfobetaines of betulinic acid that contained N,N-(dimethylammonium)butane-1-sulfonate, a new type of Zwitter-ion in a series of lupane-type pentacyclic triterpenoids, were developed in order to prepare new betulinic acid derivatives and to study the structure–biological-activity relationship.

A new zwitterionic derivative of the lupan pentacyclic triterpenoid series, viz., the sulfobetaine with a 4-(dimethylammonio)butane-1-sulfonate moiety, was synthesized by quaternization of betulin 28-(2-dimethylaminoacetate) with 1,4-butane sultone. The sulfobetaine was found to possess a dose-dependent proliferative effect toward human embrionic kidney cells HEK293 and human T-lymphocytes. Betulin chosen as a comparison compound demonstrated an effect against cells of both the tumor (HepG2, Jurkat) and the normal origin (human HEK293 and T-lymphocytes) which differ from that of the sulfobetaine, inhibiting their proliferation. The new sulfobetaine can prove to be a promising basis for the development of reparative and immunostimulating agents.

Electronic, IR, and NMR spectroscopy methods were used to study the interaction in the β-glycyrrhizic acid (GA)–2,8-dimethyl-5-[2´-(6″-methylpyridin-3″-yl)ethyl]-2,3,4,5-tetra-hydro-1H-pyrido[4,3-b]indole (Dim) system in an alcoholic medium. The complete assignment of signals in the 1H and 13C NMR spectra of Dim and GA in CD3OD was made for the individual components and for thier mixtures at different ratios. These data suggest the formation of a host–guest complex in this system. It is hypothesized that associates of GA molecules interact with Dim through Δ12,13–carbonyl group conjugated bonds in the triterpene moiety of GA that interact with the aromatic systems of the indole and pyridine moieties of Dim, as well as via an acid-base mechanism involving mainly the carboxy groups of glucuronic acid residues in the carbohydrate part of GA and the nitrogen atom of the tetrahydropyridine ring of Dim.

A series of potentially biologically active betulin derivatives containing various C-28 2-uracilacetoxy substituents were synthesized.

Palladium(II) chloro complexes with (RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-tria-zol-1-ylmethyl)pentan-3-ol (L), such as trans-[PdCl2L2], cis-[PdCl2L2], and trans-[Pd2(μ-Cl)2Cl2L2], were synthesized. The structures of their coordination cores and the coordination modes of the reagent to the metal ion via the N(4) atom of the triazole ring were established by electronic, IR, and 1H and 13C NMR spectroscopy. The ratio of RS- and RR(SS)-diastereomers in the complexes was determined from the complete assignment of signals in their 1H and 13C NMR spectra.

Baeyer-Villiger oxidation of racemic [2 +2 ]-cycloadduct derived from dichloroketene and dimethylfulvene gave 3,3-dichloro-6-(1-methylidene)-3,3a,6,6a-tetrahydro-2H-cyclopenta[b]furan-2-one, and opening of the lactone ring in the latter with (+)-α-methylbenzylamine produced diastereoisomeric amides which can be readily separated by chromatography on silica gel. The subsequent lactonization and reductive dechlorination afforded enantiomeric (−)- and (+)-6-(propan-2-ylidene)-3,3a,6,6a-tetrahydro-2H-cyclopenta[b]-furan-1-ones.

28-Triphenylmethoxylup-20(29)-ene-2,3-dione dioxime and 18α(H)-oleanane-3β,19β,28-triol upon reaction with acetylene in superbasic medium KOH-DMSO undergo intramolecular cyclization with the formation of products containing 1,2,5-oxadiazole and tetrahydrofuran fragment, respectively.

Proceeding from the [2+2]-adduct of dichloroketene and dimethylfulvene a synthesis was developed of methyl (5Z)-7-(2,2-dimethyl-4-oxo-1-oxaspiro[2.4]hept-6-en-5-yl)hept-5-enoate, the key block in the new synthetic approach to 15-deoxy-Δ12,14-prostaglandin J2.

Proceeding from the [2+2]-adduct of dichloroketene and dimethylfulvene a synthesis was developed of 6-(1-methylethylidene)-3,3a,6,6a-tetrahydro-2H-cyclopenta[b]furan-2-one, and further transformations of the latter were carried out aiming at the oxidative cleavage of the isopropylidene double bond and preparation of the corresponding cyclopentenone blocks.

Lupane-type triterpenoid derivatives containing a 2,3-annelated 1H-pyrrole or an N-vinylpyrrole moiety were synthesized by reaction of 28-OTr-lup-20(29)-en-3-one oxime and acetylene in KOH/DMSO superbase medium at atmospheric pressure.

1-[5-Acetyl-3-(methylthiomethyl)tetrahydro-3-thiopyranyl]-1-ethanone was obtained by the interaction of sodium sulfide and sodium methanethiolate with formaldehyde and acetone. The intramolecular crotonate condensation of the product leads to 4-methyl-1-methylthiomethyl-7-thiabicyclo[3.3.1]non-3-en-2-one. The participation of 3-methylthiomethyl-3-buten-2-one in the formation of a thiamono-cyclane is clarified. A probable scheme for the conversions is proposed.

Mono-and bis(methylthiomethyl) substituted derivatives of cyclopentanone and cyclohexanone were obtained on the basis of natural methylmercaptan via the alkylthiomethylation of ketones, and these derivatives were converted into the corresponding γ-hydroxysulfides and ketosulfones via reduction with sodium borohydride and oxidation with hydrogen peroxide, respectively.

The regioselectivity in the hydroboration-oxidation of ricinoleic acid derivatives only slightly depends on the configuration of the optically active center: the fraction of the resulting 1,3-diol is larger by 6–10% than that of the 1,4-isomer. The new asymmetric center has preferentially S configuration, as follows from the formation of the corresponding stereoisomeric 1,3-dioxane from the 1,3-diol and of 2,5-dialkyltetrahydrofuran from the 1,4-diol.

(2S,3S,4S)-2,3-O-Isopropylidene-4-(methoxycarbonylmethyl)cyclopentan-1-one was synthesized starting from D-ribose through methyl (Z)-3-(5-acetyl-2,2-acetoxyacetyl-2,2-dimethyl-1,3-dioxolan-4-yl)prop-2-enoate which was subjected to cyclization in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene, followed by decarboxylation.

Hydroxylamine hydrochloride efficiently reduces peroxide products of olefins ozonolysis into carbonyl compounds. Depending on the substrate character, solvent, and the treatment conditions the arising aldehydes transformed along the route aldehyde→aldoxime→nitrile→ester into individual compounds or their mixtures, or give the corresponding acetals.

The extraction of gold(III), palladium(II), and platinum(IV) with 1-[[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole from hydrochloric acid solutions into toluene has been studied. The extraction follows the anion-exchange mechanism. The concentration constants and thermodynamic parameters of the extraction reaction have been calculated. The reagent is proposed for use in the extraction of the sum of precious metals.

1H NMR study showed the possibility for intramolecular hydrogen bonding in 5(4)-hydroxy derivatives of 2,3-O-isopropylidene-β-D-ribofuranose in CDCl3. The obtained data were used to interpret differences in the 1H NMR spectra of structurally related 5-halo-2,3-O-isopropylidene-D-ribofuranosides and four newly synthesized diastereoisomeric 5-bromo-5-deoxy-4-hydroxy-2,3-O-isopropylidene-D-ribofuranosides.

Methyl-4-methylene-2,3-O-isopropylidene-β-D-ribofuranoside prepared from D-ribose reacted in a system NBS-THF-H2O to give a mixture of stereoisomeric products of regioselective bromohydroxylation of a double bond. The reaction involved a hydrolysis of the glycoside bond, but the acetonide protective group was retained. The mechanism of the selective hydrolysis originating from the ring-chain tautomerism of bromohydrins obtained was proved by the 1H NMR spectra of the steroisomeric methyl-5-deoxy-5-bromo-4-hydroxy-2,3-O-isopropylidene-β-D-ribofuranosides. By crotonic cyclization of the formed masked 1,4-dicarbonyl compounds at heating in benzene in the presence of neutral Al2O3 a new chiral cyclopentenone block, 2-bromo-4,5-isopropylideneoxycyclopent-2-en-1-one, was obtained in a low yield.

It was found that the heating of 3,7-dimethyl-5-thianonan-2,8-dione at 50°C in ethanol in the presence of potassium hydroxide yields 1,4,5-trimethyl-7-thiabicyclo[2.2.2]octan-2-one as a mixture of 5-exo-and 5-endo-isomers in the ratio of 5:1. The oxidation of thiabicyclooctanone with hydrogen peroxide and its reduction with sodium borohydride result in 1,4,5-trimethyl-7-thiabicyclo[2.2.2]octane-2-one-7,7-dioxide and 1,4,5-trimethyl-7-thiabicyclo[2.2.2]octane-2-ol, respectively.

Methyl (1S,2S,3R,4R)-2,3-isopropylidenedioxy-5-iodomethyl-2-tetrahydrofurylacetate prepared in two stages from D-ribose acetonide underwent a series of uncommon transformations under the treatment with bases providing the following different products depending on the base applied: methyl 3-(5-acetyl-2,2-dimethyl-1,3-dioxol-4-yl)propionate (DBU), methyl 2,3-isopropylidenedioxy-7-oxabicyclo[2.2.1]heptane-6-carboxylate (t-BuOK), methyl {(5R)-2,2-dimethyl-5-[(2R)-oxiranyl]-1,3-dioxolan-4-ylidene}propionate and methyl-(E)-3-{(4S,5R)-2,2-dimethyl-5-[(1R)-(2-oxiranyl)]-1,3-dioxolan-4-yl}-2-propenoate (t-BuOK and LDA).

Halocyclization of mesylates or tosylates of 2-(cycloalk-2-en-1-yl)anilines gives N-methanesulfonyl-or N-toluenesulfonyl-1-halo-1,2,3,4,4a,9a-hexahydrocarbazoles, heating of which in DMF at 160°C or in piperidine at 110°C leads to 4,4a,9,9a-tetrahydro-3H-carbazoles. Heating N-methanesulfonyl-1-iodo-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole in DMF at 180—200°C gives 1,3a,4,9b-tetrahydrocyclopenta[b]indole, while in the presence of an ortho-methyl substituent the dehydroiodination reaction proceeds in piperidine at 110°C in high yield. The effect of the nature of the ortho substituent of N-methyl-1-iodo-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole on the conformational equilibrium of the cyclopentane ring has been established by 1H NMR spectroscopy.

Рассмотрены вопросы надежности и функциональной безопасности газотурбинных установок наземного применения. Проведенаформализация ранее разработанных моделей рисков газотурбинных установок наземного применения и их процессов. Предложенметод управления неопределенностью сложных технических систем и их процессов в условиях ограниченных ресурсов, основанныйна методе оценки рисков и методе выбора контрмер, что позволяет сформировать область критичных рисков для исследуемой сложной технической системы. Усовершенствован метод выбора контрмер из альтернативных вариантов, основанный на методе анализа иерархий и методе приемлемого риска ALARP, поскольку применение контрмер осуществляется за счет реально имеющихся (ограниченных) ресурсов. Проведена классификация контрмер по времени применения и по объекту воздействия. Выделенные типы послужили критерием сравнения при выборе контрмер из альтернативных вариантов. Создана сводная таблица соотношения контрмер различных типов. Метод выбора контрмер из альтернативных вариантов позволяет сделать вывод в условиях ограниченных ресурсов и дать экономически обоснованную оценку при принятии решения об уровне приемлемого риска. Полученные методы апробированы для оценки рисков процесса испытаний газотурбинных установок наземного применения., The article deals with the questions of reliability and functional safety of the gas turbine units for terrestrial usage. Previously developedrisk models of the gas turbine units for terrestrial usage and processes are formalized. Authors propose the method of managing uncertainty ofcomplex technical systems and their processes in resource-limited settings. It is based on the method of risk assessment and the method for choice of alternative countermeasures. It allows to form the risk critical area for the complex technical systems. The method for choice ofalternative countermeasures improved. It is based on the Analytic Hierarchy Process and the method of acceptable risk ALARP, since theapplication of countermeasures realize at the expense actually available (limited) resources. Countermeasures were classified by time ofapplication and impact object. Dedicated types served as a compare criterion of the method for choice of alternative countermeasures. Asummary table was created for ratio of different types of countermeasures. The method for choice of alternative countermeasures allows to make a conclusion in resource-limited settings and provides economically reasonable estimate of the decision about the level of acceptable risk. The derived methods are tested for the GTU tests process risk assessment.

The addition of dichlorocarbene generated under phase transfer catalysis conditions to the double bond of betulonic acid occurs stereoselectively and is accompanied by transformation of the carboxy group leading to the dichloromethyl ester and chloride of 3-oxo-20,29-(dichloromethano)lupan-28-oic acid. Together these products, the chloride of the starting betulonic acid is formed depending on the reaction conditions. The reaction of dichlorocarbene with methyl betulonate leads to the corresponding cyclopropane adduct in a quantitative yield.

The possibility of functionalizing the alkyl part of ricinolic acid using the Barton reaction was investigated.

2-Amino derivatives of levoglucosenone were prepared by reaction of the 2-methanesulfonyl (or p-toluenesulfonyl) derivatives with ammonia, methylamine, or octylamine under various conditions. The analogous reaction did not occur for saturated derivative 15. The 2-amino-3,4-dihydro derivative was prepared by catalytic hydrogenation of unsaturated amine 9.

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.

The reactions of 5-allenyl-2,3,5-trichloro-4,4-dimethoxycyclopent-2-en-l-one and related compounds with I2 were studied. The stereochemistry of the resulting 1,2-adducts with I2 at the terminal double bond of the allenic fragment depends in a complex way on the character of functionalization in the cyclopentene fragment of the starting molecule.

Regiospecific C55 -halogenation with retention of configuration occurred upon Beckman fragmentation of levoglucosenone oxime using SOCl2 or PBr3. On the other hand, the oxime of its dihydro derivative gave under these conditions the C6 - substitution product. A stereoselective synthetic scheme for (+)-γ-pelargonolactone, an attractant for the rice and corn weevils Sitophiltus zeamais, was developed from the fragmentation product of levoglucosenone oxime.

Oxidation of betulin by pyridinium dichromate, pyridinium chlorochromate, and K2Cr2O7 -H2SO4 in the presence of tetrabutylammonium bromide was studied. Products of regioselective C-3, C-28-, and exhaustive oxidation, 28-hydroxylup-20(29)-3-one, 3β-hydroxy- and 3-oxolup-20(29)-en-28-al were obtained.

1) Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, 450054 Ufa, pr. Oktyabrya,71, fax (3472) 35 60 66, e-mail: chemorg@anrb.ru; 2) N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, SiberianDivision, Russian Academy of Sciences, 630090 Novosibirsk, pr. Lavrent1 eva, 9, fax (3832) 34 47 52, e-mail:gtolstik@nioch.nsc.ru. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 129-134, March-April, 2002. Originalarticle submitted March 28, 2002.154 0009-3130/02/3802-0154$27.00 2002 Plenum Publishing Corporation

Treatment of the ozonization products from N-acetyl- or 2-methyl-N-trifluoroacetyl-6-(cyclopent-1-enyl)anilines with NaBH4 gives 6-methyl-2-tetrahydropyranylaniline. When treated with Me2S, the ozonization products yield the corresponding oxoaldehyde dimethyl acetals. The oxidation of N-acetyl-2-(cyclopent-1-enyl)- or -(cyclohex-1-enyl)anilines with H2O2 in HCOOH affords ω-(2-acetamidophenyl)-5-oxopentanoic or -6-oxohexanoic acid, respectively. The reaction of N-acetyl-2-(cyclopent-1-enyl)aniline with H2O2 in the presence of Na2WO4 and H3PO4 gives 3,1-benzooxazine in high yield.

Analog of chlorvulone II containing an extra chlorine atom at C11 was synthesized starting with 1,4-dioxa-6,7-dichlorospiro[4.4]non-6-ene.

4-Hydroxymethyl-2-methyl-2-(1-methylthiomethyl)vinyl-1,3-dioxolane, 2-methyl-2-(1-methylthiomethyl)vinyl-1,3-dioxolane, and 3-methylthiomethyl-3-buten-2-one were synthesized from bis(methylthiomethyl)propan-2-one, including ketolization, and thiol elimination steps followed by acid hydrolysis. The synthesized compounds are of interest as biocides and intermediate products in organic synthesis.

The opening of the cyclobutanone ring in compound (I) proceeds readily under the action of chiral amine (II) to afford inseparable diastereomeric amides (III) and (IV), which are converted into separable lactams (V) and (VI).

Allenyl-2,3,5-trichloro-4,4-dimethoxy-2-cyclopentenone and 5-allenyl-2,3,5-trichloro-4,4-dimethoxy-1-(2-propynyl)-2-cyclopentenol react with iodine in methylene chloride at room temperature to give the corresponding 5-[(E)-2,3-diiodo-1-propenyl] derivatives.

By reaction of 6,7-dichloro-1,4-dioxaspiro[4.4]non-6-en-8-one with NaI and LiBr in boiling acetylacetone or methyl butyl ketone the corresponding 3-iodo and 3-bromo derivatives of cyclopentenone were prepared.

The hydroalumination of a series of alkenes and some fused aromatic hydrocarbons by the LiAlH4 · 3AlBr3 system in low-polar solvents was studied. Alkenes with mono-, di-, tri-, and tetraalkyl substituted, mono- and diaryl substituted double bonds and anthracene react at room temperature to give the corresponding dibromoaluminoalkanes in high yields. Benzylidenefluorene, tetraphenylethylene, naphthalene, and phenanthrene do not undergo hydroalumination under these conditions. Camphene, bicyclo[3.2.1]oct-2-ene, and norbornene afford the corresponding organoaluminum compounds with high stereoselectivity. Oxidation and halo- and acyldemetallation of the resulting alkyl- and arylalanes were carried out.

Alkenylphenyl-substituted quinazolinones were prepared by reactions of 2-methyl-4H-3,1-benzoxazin-4-one with o- and p-alkenylanilines.

Heating of bicyclic alkenylcyclopropanes 2a-q in DMF with LiI results in good yields of cyclopentenes or conjugated dienes depending on a subsrate structure.