Showing papers on "Epoxide published in 1988"

1,N2-ethenodeoxyguanosine as a potential marker for DNA adduct formation by trans-4-hydroxy-2-nonenal.

Abstract: The reaction of trans -4-hydroxy-2-nonenal, a major α,β-unsaturated aldehyde released during lipid peroxidation, with deoxyguanosine under physiological conditions was investigated in order to assess its DNA damaging potential. This aldehyde was dissolved in tetrahydrofuran (THF) prior to addition to the reaction mixture. The results showed that structurally different adducts were formed in these reactions depending on the THF used. Using THF unprotected from light, reactions yielded adducts 1 to 6. Adduct 1 was characterized as 1, N 2 -ethenodeoxyguanosine (5,9-dihydro-9-oxo-3-β-d-deoxyribofuranosylimidazo[1,2- a ]purin e) by its UV, proton nuclear magnetic resonance, and mass spectrum and by comparison to the corresponding guanosine and guanine adducts reported in the literature. The UV spectrum of adduct 4 was indicative of a substituted 1, N 2 -etheno derivative. Adducts 2, 3, 5, and 6 were essentially identical in UV spectra and appeared to be N 2 -substituted deoxyguanosine diastereomers. At room temperature adducts 2, 3, 5, and 6 were converted quantitatively to a single product at pH 10.5. This product was shown to be identical to 1, N 2 -ethenodeoxyguanosine (adduct 1). Analogous conversions to 1, N 2 -ethenoguanine were also observed for the corresponding guanine adducts. Using THF that had been protected from the light, however, the reactions of trans -4-hydroxy-2-nonenal with deoxyguanosine gave three major adducts, 7, 8, and 9. These adducts possessed UV spectra similar to that of 1, N 2 -propanodeoxyguanosine and were not converted to 1, N 2 -ethenodeoxyguanosine upon base treatment. Evidence obtained suggests that adducts 1 to 6 were formed from the reaction of deoxyguanosine with the epoxide of trans -4-hydroxy-2-nonenal generated in the presence of hydroperoxide in the light unprotected THF, whereas adducts 7 to 9 were formed by direct Michael addition. Adducts 1 to 6 were formed presumably as a result of nucleophilic addition of the exo -amino of deoxyguanosine to the aldehydic group of the epoxide of trans -4-hydroxy-2-nonenal. Base treatment of these adducts facilitated subsequent cyclization and eliminations and finally gave 1, N 2 -ethenodeoxyguanosine. These results demonstrated that trans -4-hydroxy-2-nonenal readily forms adducts with deoxyguanosine either by direct Michael addition or via its epoxide formation. The facile conversion of some of these adducts to a single adduct suggests that 1, N 2 -ethenodeoxyguanosine may provide a simple and useful marker for assessing potential DNA damage by trans -4-hydroxy-2-nonenal and related alkenals associated with lipid peroxidation.

Isolation and characterization of natural allene oxides: unstable intermediates in the metabolism of lipid hydroperoxides

Abstract: Allene oxides are unstable epoxides that have been implicated as intermediates in the biotransformation of hydroperoxyicosatetraenoic acids and related hydroperoxides to ketols and cyclopentenones. Direct proof of the structure of the putative allene oxide intermediates has been hampered by their extreme instability under the conditions of their biosynthesis (t1/2 approximately 15-30 sec at 0 degree C and pH 7.4). We now report the isolation and structural elucidation of allene oxides prepared from the (13S)-hydroperoxides of linoleic and linolenic acids. The compounds were biosynthesized by using a very active enzyme preparation from flaxseed. After a 5-sec incubation at 0 degrees C, the allene oxide metabolites were extracted and purified as the methyl ester derivatives at -15 degrees C. The structures were established by UV, CD, NMR, and oxygen-18 labeling experiments. 12,13(S)-Oxido-9Z,11-octadecadienoic acid is derived from linoleic acid, and 12,13(S)-oxido-9Z,11,15Z-octadecatrienoic acid is from linolenic acid. Analysis of the breakdown products formed on exposure to water led to identification of hydrolysis and cyclization products previously characterized as enzymic derivatives of the (13S)-hydroperoxides in flaxseed. Our results give direct proof of the structure of the allene oxide intermediates and should facilitate further investigation of the metabolism of this class of epoxide to prostaglandins, clavulones, and other stable end products.

Mechanistic studies of alkene epoxidation catalyzed by nickel(II) cyclam complexes. Oxygen-18 labeling and substituent effects.

Abstract: The oxidations of cyclohexene and various aryl-substituted alkenes are catalyzed by the cyclam (1,4,8,11-tetraazacyclotetradecane) complex of Ni(NO/sub 3/)/sub 2/ with iodosylbenzene as terminal oxidant. Epoxides are the major products; however, small amounts of ring-opened products, over-oxidation to ketones or aldehydes, and allylic oxidation of cyclohexene are also observed. E olefins are more reactive than the corresponding Z olefins in contrast to the results of iron porphyrin catalysis, and kinetic studies of para-substituted styrenes indicate that the reaction is facilitated by electron-donating substituents. Labeling studies with PhI/sup 18/O confirm that the epoxide oxygen is derived from PhIO while allylic oxidation and over-oxidation products involve both PhIO and exogenous sources of oxygen. A pericyclic mechanism for the formation of PhCHO is proposed along with the intermediacy of a high-valent nickel-oxo complex as the active oxidant. These results are discussed in light related transition-metal/PhIO oxidation mechanisms.

Enantioselective ring cleavage of meso-epoxides with B-halodiisopinocampheylboranes

Abstract: : B-Halodiisopinocampheylboranes, IpcBX, in particular the bromide 1b, and the Iodide 1c, differentiate between the enantiotopic carbon-oxygen bonds of meso-epoxides to furnish 1,2-halohydrins of moderate to excellent enantiomeric purity. Thus (-)-(1R, 2R)-2-bromocyclohexanol, (-)-(1R, 2R)-2-iodocyclohexanol, (-)-(1R, 2R)-2-iodocyclohex-4-en-1-o1 and (-)-(1R, 2R)-2-bromocyclohex-4-en-1-o1 are obtained in 84%, 91%, 63% and 95% ee respectively from the corresponding meso-epoxides and haloborane reagents. Simple recrystallization from pentane then gives halohydrins of essentially 100% ee; cis-2-butene oxide and cis-3-hexene oxide furnish the corresponding (1R, 2R)-iodohydrins in 78 and 69% ee respectively. In all cases the S carbon of the meso-epoxide is selectively cleaved. This is the first example of enantioselective ring cleavage of meso-epoxides to obtain optically active 1,2-halohydrins. Keywords: Asymmetric synthesis.

Cis-trans isomerization of epoxides catalyzed by ruthenium(II) porphyrins

Abstract: Bis(tetrahydrofuran)(5,10,15,20-tetramesitylporphyrinato)ruthenium(II) (Ru/sup II/TMP(THF)/sub 2/) and the corresponding p-tolylporphyrin (Ru/sup II/TTP(THF)/sub 2/) have been found to catalyze the cis-trans isomerization of epoxides under mild conditions. For ..beta..-methylstyrene oxide an equilibrium ratio of 5.4:1 (trans/cis) was achieved with either isomer indicating a free energy difference of 1 kcal/mol. Inhibition of the isomerization by added olefins was observed and attributed to olefin coordination to ruthenium(II). cis-..beta..-Methylstyrene oxide readily formed and adduct with Ru/sup II/TMP(CO), while the trans isomer did not. The isomerization of trans-(1S,2S)-..beta..-methylstyrene oxide gave only cis-(1R,2S)-..beta..-methylstyrene oxide gave only the cis-(1R,2S)-..beta..-methylstyrene oxide. A mechanism for epoxide isomerization involving homolytic cleavage of the C/sub 1/-O bond to give carbon radical intermediate is proposed.

Reaction of hematin with allylic fatty acid hydroperoxides: identification of products and implications for pathways of hydroperoxide-dependent epoxidation of 7,8-dihydroxy-7,8-dihydrobenzol[a]pyrene

Abstract: Reaction of 10-hydroperoxyoctadec-8-enoic acid (10-OOH-18:1) (50 microM) with hematin (0.5 microM) in sodium phosphate buffer containing Tween 20 (200 microM) generates 10-oxooctadec-8-enoic acid, 10-oxodec-8-enoic acid (10-oxo-10:1), and 10-hydroxyoctadec-8-enoic acid in relative yields of 79, 4, and 17%, respectively. The product profile and relative distribution are unaffected by 1 mM butylated hydroxyanisole. Approximately 5% of the hydroperoxide isomerizes from the 10- to the 8-position. 10-Oxo-10:1 most likely arises via beta-scission of an intermediate alkoxyl radical to the aldehyde and the n-octyl radical. To test this, 10-hydroperoxyoctadeca-8,12-dienoic acid was reacted with hematin under identical conditions. 10-Oxooctadeca-8,12-dienoic acid, 10-oxodec-8-enoic acid, and 10-hydroxyoctadeca-8,12-dienoic acid are formed in relative yields of 50, 45, and 5%, respectively. The product ratios are constant with time and hydroperoxide to catalyst ratio and unaffected by inclusion of phenolic antioxidants. The higher yield of 10-oxo-10:1 from 10-OOH-18:2 compared to 10-OOH-18:1 is due to the higher rate of beta-scission of the intermediate alkoxyl radical from the former to the resonance-stabilized octenyl radical. Two products of reaction of the 2-octenyl radical with O2, octenal and octenol, were detected in 10% yield relative to 10-oxo-10:1. Inclusion of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) led to epoxidation by both 10-OOH-18:1 and 10-OOH-18:2. Studies with isotopically labeled hydroperoxide or O2 indicated approximately 65% of the epoxide oxygen was derived from O2 and 35% from hydroperoxide oxygen, consistent with the involvement of peroxyl free radicals as the oxidizing agents. The available evidence indicates that hematin reduces the fatty acid hydroperoxides homolytically to alkoxyl radicals that are oxidized to ketones, reduced to alcohols, or undergo beta-scission to aldehydes. Carbon radicals generated during these reactions couple to O2, generating peroxyl free radicals that epoxidize BP-7,8-diol. The smaller percentage of epoxidation that results from hydroperoxide oxygen may arise from oxidation of the hydroperoxide group to peroxyl radicals or from heterolytic cleavage of the hydroperoxide to alcohol and an iron-oxo complex.

Latent, curable, catalyzed mixtures of epoxy-containing and phenolic hydroxyl-containing compounds

Abstract: Storage stable compositions are disclosed which comprise an epoxide containing compound, a phenolic hydroxyl containing compound, and a catalyst compound for catalyzing the reaction between epoxide groups and aromatic hydroxyl groups which catalyst comprises the product resulting from contacting an onium salt, amine, or amine salt with an acid or a salt of an acid having a weak nucleophilic anion.

Polyethers, process for their preparation and lubricants containing these polyethers

Abstract: Monofunctional polyethers having hydroxyl groups contain as built-in terminal groups or monomers (a) 1 to 30% by weight of one or more C4 - to C24 -alkylmonophenols, (b) 1 to 30% by weight of one or more C8 - to C24 -monoalkanols, (c) 1 to 30% by weight of one or more C10 - to C20 -1,2-epoxyalkanes and (d) 45 to 80% by weight of propylene oxide or a lower alkylene oxide mixture consisting mainly of propylene oxide the sum of components (a) to (d) adding up to 100% by weight, and have average molecular weights of 600 to 2,500. These polyethers are prepared by anionic epoxide polymerization and used as lubricants and components of lubricants.

Stereospecific epoxidation by air of cholest-5-ene derivatives catalysed by a ruthenium porphyrin

Abstract: A ruthenium porphyrin catalyses the epoxidation of several cholest-5-ene derivatives by air in high yield and with nearly complete β-stereospecificity; C-3-unprotected cholesterol is unaffected, but cholesteryl acetate gives nearly pure (>99%) 5β,6β-epoxide.

Stereospecific synthesis of squalenoid epoxide vinyl ethers as inhibitors of 2,3-oxidosqualene cyclase

Abstract: The stereospecific synthesis of squalenoid epoxide vinyl ethers with an isopentyloxy group is described. The synthesis involves the preparation of the C22 squalenoid aldehyde bromohydrin (15) by a new method via a one-step cleavage of lipophilic epoxides using periodic acid in diethyl ether, and the preparation of (1-isopentyloxyethyl)diphenylphosphine oxide (24). The structure of this compound has been confirmed by X-ray analysis. The configuration of vinyl ethers, synthesized using a Wittig-Horner reaction, has been determined by 13C n.m.r. Biological results show that vinyl ethers (5) and (27) are competitive inhibitors of 2,3-oxidosqualene cyclase from rat liver.

Characterization of 7,12-dimethylbenz[a]anthracene-adenine nucleoside adducts.

Abstract: Chromatographic comparisons were made between radioactive adducts derived from the DNA of cells treated with [3H]7,12-dimethylbenz[a]anthracene and adducts derived from calf thymus DNA or nucleotides which had been treated in vitro with the synthetic syn 3,4-dihydrodiol 1,2-epoxide of this same carcinogen. This confirmed that three of the adducts formed in cells were derived from reaction of this particular dihydrodiol epoxide with deoxyadenosine while a fourth adduct was derived from its reaction with deoxyguanosine. After reaction of the dihydrodiol epoxide with polyadenylic acid, two ribonucleoside adducts were characterized by spectroscopic methods and were shown to have arisen from the cis opening of the epoxide ring at C1 by the amino group of adenine residues.

Synthesis of selenium-containing binaphthyls and their application to the asymmetric ring-opening of cyclohexene oxide

Abstract: Three novel selenium-containing binaphthyl compounds (1–3) have been synthesized in optically active form and applied to the asymmetric ring-opening reaction of cyclohexene oxide (4), resulting in enantiomeric excesses of between 16 and 50%.