Ozonolysis Products Research Articles

ChemInform Abstract: Products of Ozonolysis of L‐1,4‐Cyclohexadienylalanine. Intramolecular Cyclization and Cyclization with Hydroxylamine. The Synthesis of Two Isomers of L‐Isoxazolylalanine.

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Synthesis of Hydroxy(or Hydroperoxy)-Substituted 1,2,4-Trioxacycloalkanes by the Ozonolysis of Unsaturated Hydroperoxy Acetals

Ozonolyses of unsaturated hydroperoxy acetals 4a−k gave in each case the mixtures of products containing the corresponding trioxanes 8a−f and 12e,f, trioxepanes 12g−i, trioxocane 12j, and trioxonane 12k. By choosing the proper conditions of the ozonolysis, the desired cyclic peroxide was selectively obtained in moderate to good yield. Alternatively, acid-catalyzed cyclization of the methanol-derived ozonolysis products 13h and 13j provided the corresponding trioxepane 12h and trioxocane 12j, respectively.

Analysis of Ozonolysis Products of Benzo[A]Pyrene With Capillary Gas Chromatography Mass Spectrometry and Liquid Chromatography Mass Spectrometry

Various chromatographic techniques coupled with mass spectrometry were used for the analysis of polar products after ozonolysis of benzo[a]pyrene (BaP), including CGC-HRMS, thermospray-LC-MS and APCI-LC-MS. The simulation of atmospheric degradation of benzo[a]pyrene by ozone was carried out on glass fiber filters and BaP-coated soot. The drawback of GC/MS is the low sensitivity for these analytes, the advantages are the higher separation performance and the possibility of electron impact (El) spectra. In comparison, APCI-LC-MS is by far more sensitive with detection limits in the absolute picogram range, despite the lack of structural information. No qualitative difference between the ozonolysis products of BaP deposited on glass fiber filters or soot surfaces was observed. Reaction products consist mainly of quinones and carboxylic acids. A number of compounds cannot be identified yet and require further investigation. With the APCI-LC-MS, the formation of BaP degradation products was confirmed on real samples of air particulate matter.

Ozone Does Not React with Human Erythrocyte Membrane Lipids

Ozone was applied to sealed red cell ghost membranes at the rate of 95 nmol/min for periods up to 20 min. Acetylcholine esterase, on the outer face of the membrane, was inhibited up to 20%. Glyceraldehyde-3-phosphate dehydrogenase, on the inner surface of the membrane, was inhibited up to 87%. These differences reflected the inherent susceptibilities of the two enzymes and the presence or absence of the membrane barrier. Analysis of the total lipids of the ozone-treated ghosts showed no significant change in the distribution of lipid classes and no significant change in the fatty acid composition. There was no significant change in the fatty acid composition of the phosphatidylcholine fraction. There was a slight increase in 18:0 and 20:2 + 20:3 in the phosphatidylethanolamine fraction. There was no change in the molecular species distribution of the phosphatidylcholine or the phosphatidylethanolamine fraction. There was no evidence for the formation of the phospholipid ozonolysis product, 1-acyl-2-(9-oxo-nonanyl) derivatives of glyceryl-phosphoryl choline. There was no decline in the amount of cholesterol in the lipids derived from ozone-treated red cell membranes. Treatment of red cell ghost membranes and, by implication, the plasma membrane of cells by ozone therefore oxidizes peripheral proteins before it oxidizes lipids.

Products of ozonolysis of L-1,4-cyclohexadienylalanine. Intramolecular cyclization and cyclization with hydroxylamine. The synthesis of two isomers of L-isoxazolylalanine

Abstract Protected L-phenylalanine was reduced to L-1,4-cyclohexadienylalanine followed by ozonolysis of the unsaturated ring. Intramolecular cyclization of the ozonolysis product occured upon treatment with acid. The cyclization of the product of ozonolysis with hydroxylamine was studied as well. The formation of both 5- and 3-isoxazolylalanine is demonstrated. Mechanism of formation of these products and structure of intermediates are discussed.

Hanishenols A-B, novel linear or methyl-branched glycerol enol ethers of the axinellid sponge Acanthella carteri (= Acanthella aurantiaca) from the Hanish Islands, southern Red Sea

The axinellid sponge Acanthella carteri Dendy, 1889 (= Acanthella aurantiaca Keller, 1889) from the Hanish Islands, Yemen, on EtOH extraction followed by FC and HPLC purification gave the first example of branched glycerol enol ether, hanishenol B ( 3) alongside a major unbranched analogue, hanishenol A ( 1). Their structures were elucidated from NMR and MS spectra and through the ozonolysis product of 1, while the absolute configuration was assigned from exciton coupling with the dibenzoate derivative 2.

Elaidic and trans-vaccenic acids in plasma phospholipids as indicators of dietary intake of 18:1 trans-fatty acids.

Octadecenoic (18:1) trans-fatty acid fractions from margarine, butter and plasma phospholipids (PL) were isolated by silver ion TLC, and nine positional isomers (n-11-n-3) were identified by GC-MS based on their ozonolysis products. The GC analysis of the isolated fractions gave similar peak profiles and separated seven trans-isomers (n-11-n-6 and n-3). Without a preceding isolation step, the reproducibility of the GC method for plasma PL elaidic (18:1 n 9 trans) and trans-vaccenic acids (n-7) was 3.4 and 2.7% (R.S.D.), respectively. These trans-isomers were rapidly incorporated and cleared in plasma PL and they closely reflected both increased and decreased intake of 18:1 trans-fatty acids during moderate fat substitutions. Significant associations between high-density lipoprotein cholesterol (HDL-C) and PL elaidic and trans-vaccenic acids appeared in habitual margarine users only.

Reaction of Ozone with Enzymes of Erythrocyte Membranes

Ozone is a widespread component of polluted air. It is the cause of many adverse effects on the lung such as decreased athletic performance and exacerbation of asthma. Ozone inactivated acetylcholine esterase (AChE) both in intact washed human erythrocytes and in ghosts prepared from the erythrocytes. This is consistent (a) with the location of AChE on the outer face of the membrane and (b) with the change in structure of AChE when amino acids were oxidized. The glyceraldehyde-3-phosphate dehydrogenase (G3PDH) of intact washed erythrocytes was unaffected by ozone. However, ozone severely inactivated G3PDH of ghosts, much more severely than AChE in ghosts. This result raised questions about the relative permeability of intact erythrocytes and ghosts and also about the inherent susceptibility of the two enzymes. Inhibition of the ozone-treated erythrocyte AChE with the competitive inhibitor trimethyl-(p-aminophenyl) ammonium chloride was measured. The inhibited enzyme had a higherKMand slightly lowerVmaxthan the control. Ozone did not affect theKMof the uninhibited enzyme but decreased theKMof the inhibited enzyme. Ozone decreased theVmaxof both the inhibited and the uninhibited enzyme. TheKIwas unchanged by the treatment with ozone. This suggested that the active site of the enzyme was not affected by ozone, but other features of the protein were changed by ozone. The effects of products of lipid ozonolysis [hydrogen peroxide, nonanal, and 1-palmitoyl-2-(9-oxononanyl)-sn-3-glycerophosphorylcholine (PN1PC)] were tested on the ghost preparations. The ozonolysis products were tested at concentrations equivalent to calculated amounts that could have been produced by ozone. Hydrogen peroxide had no effect on the G3PDH and AChE. Nonanal slightly increased the permeability of the ghost membrane, as judged by the increase in rate of G3PDH in the absence of Triton X-100, but did not inhibit enzyme activity. PN1PC increased the permeability of the ghosts, as judged by the increase in rate of G3PDH in the absence of Triton X-100. There was also an increase in the activity of G3PDH in the presence of Triton X-100. AChE was not inhibited by ozone in the presence or absence of Triton X-100.

Decomposition of Terpenes by Ozone during Sampling on Tenax

The ozonolytic decomposition of terpenes and terpenoids during sampling on Tenax is investigated in an artificial air system at ambient concentration levels. The detrimental effect of 8-150 ppbv ozone depends on the chemical structure of the compounds: saturated terpenoids such as 1,8-cineole, camphor, and bornyl acetate are unaffected by ozone. The terpenes and terpenoids which containing one C-C double bond are slightly decomposed in the order camphene < β-pinene ≈ myrtenal < α-pinene < sabinene ≈ citronellal. The compounds containing two or more double bonds are significantly decomposed in the order d-limonene ≈ citral < linalool < β-ocimene < terpinolene << α-terpinene ≈ β-caryophyllene. For α-pinene, sabinene and d-limonene, their ozonolysis products are found on the tubes: pinonaldehyde, 5-(1-methylethyl)bicyclo[3.1.0]hexan-2-one, and 3-(1-methylethenyl)-6-oxoheptanal. The analytical recoveries are significantly enhanced for many compounds when the sampling duration is reduced from 10 min to 30 s, explained by the time available for ozonolysis. A miniature ozone scrubber with multiple layers of MnO(2)-coated copper nets was developed and thoroughly tested. The optimal number of plies is found to be 8, which ensures quantitative recoveries for all test compounds except α-terpinene, β-caryophyllene, citral, and citronellal. The results that are reported here call into question previous data on terpenes and terpenoids and/or their oxidation products where measurements have been carried out without the prior removal of ozone.

Pheromones of insects and their analogs. LII. Sythesis of dodec-9-en-1-yl and tetradec-11-en-1-yl acetates from the products of the partial ozonolysis of cycloocta-1z,5z-diene and cyclodeca-1e,5z-diene

A new approach to the synthesis of octane-1, 8- and decane-1,10-diols based on the partial ozonolysis of cyclic oligomers has been developed.

Transformation of 1-alkyl-substituted indene ozonides and the corresponding solvent-derived ozonolysis products to tricyclic peroxides: Isolation and characterization of novel hexoxecane derivative

Acidolysis of 1-alkyl-substituted indene ozonides 3a,c,d or the corresponding solvent-derived ozonolysis products 5a-d gave the hexoxecane derivatives 4a-d. The structure of the compound 4a was unambiguously established by the X-ray crystallographic analysis, which demonstrated that the hexoxecane 4a is derived from dimerization of molecules of 3a or 5a of the same configuration.

Products of Ozonolysis of Aromatic Compounds in Aqueous Solution Containing Nitrite Ion

Abstract Aqueous solutions of 4-chlorophenol, 2,4-dichlorophenol, methoxybenzene, 1-naphthol, and naphthalene at a concentration of 0.5-1 × 10−4 M reacted with two equivalents of ozone at pH 7.25-10.65 to form various oxidation products. When the reactions were conducted in the presence of nitrite ion (0.5-1.0 × 10−4 M), a nitration reaction occurred with three of the five aromatic compounds (4-chlorophenol, 2,4-dichlorophenol, and 1-naphthol). Aromatic compounds that undergo nitration under the conditions of the experiments have a higher reaction rate than that for the reaction of ozone and nitrite ion.

Structures of ozonolysis products of methyl oleate obtained in a carboxylic acid medium

AbstractHigh‐performance liquid chromatography‐mass spectrometry (LC‐MS) and nuclear magnetic resonance spectrometry (NMR) were applied to the analysis of organic peroxide mixtures, which were labile and tended to decompose during analysis. The ozonolysis reaction of methyl oleate gives a peroxide mixture, and, finally, mono‐ and dibasic acids are obtained by subsequent oxidation. In this study, methyl oleate was ozonized in a nonanoic acid medium, one of the final reaction products. The reaction products were directly analyzed by LC‐MS equipped with a frit‐fast atom bombardment interface. The molecular ion peak of each peroxide was clearly observed, and its molecular weight was readily determined. On the other hand, each peroxide was fractionated by high‐performance liquid chromatography and submitted to structural analysis by NMR. Both results indicated that the reaction products include four peroxidic species: 1,2,4‐trioxolaneI, peroxide oligomerII, 1‐acyloxyalkyl‐1‐hydroperoxideIII, and 1‐acyloxyalkyl‐1′‐hydroxyalkyl peroxideIV, as well as an aldehydeV. Ozonolysis of methyl oleate in the absence of solvent produces mainlyI, while that in the presence of a carboxylic acid solvent characteristically produces mainlyIII andIV derived from the solvent.Bis(1‐acyloxyalkyl‐1‐alkyl) peroxide, which was reported previously as a ozonolysis product of methyl oleate, was concluded to beIV in this study.

Sex attractants of geometrid and noctuid moths: Chemical characterization and field test of monoepoxides of 6,9-dienes and related compounds

(Z,Z)-6,9-Dienes with straight C18-C23 chains were synthesized from linoleic acid, and a C17 chain was synthesized by hydrogenation of the corresponding 6,9-diyne prepared from propargyl alcohol. Oxidation of the homoconjugated dienes withm-chloroperoxybenzoic acid yielded a 1:1 mixture of two monoepoxides that could be separated by repeated medium-pressure liquid chromatography with a Lobar column. The chemical structure of each positional isomer was confirmed by analyses of the ozonolysis products, and the isomers showed characteristic(13)C signals in their NMR spectra and fragment ions in their EI mass spectra. In addition to the (Z,Z,Z)-3,6,9-trienes with straight C18-C23 chains and their monoepoxides, field tests using single source lures incorporating one of the above seven dienes and 14 monoepoxymonoenes were carried out in a forest in Tokyo from 1992 to 1994. Consequently, attraction of six geometrid species and five noctuid species was observed for the first time.

Airway epithelial cell responses to ozone injury.

The airway epithelial cells is an important target in ozone injury. Once activated, the airway epithelium responds in three phases. The initial, or immediate phase, involves activation of constitutive cells, often through direct covalent interactions including the formation of secondary ozonolysis products--hydroxyhydroperoxides, aldehydes, and hydrogen peroxide. Recently, we found hydroxyhydroperoxides to be potent agonists of bioactive eicosanoid formation by human airway epithelial cells in culture. Other probable immediate events include activation and inactivation of enzymes present on the epithelial surface (e.g., neutral endopeptidase). During the next 2 to 24 hr, or early phase, epithelial cells respond by synthesis and release of chemotactic factors, including chemokines--macrophage inflammatory protein-2, RANTES, and interleukin-8. Infiltrating leukocytes during this period also release elastase, an important agonist of epithelial cell mucus secretion and additional chemokine formation. The third (late) phase of ozone injury is characterized by eosinophil or monocyte infiltration. Cytokine expression leads to alteration of structural protein synthesis, with increases in fibronectin evident by in situ hybridization. Synthesis of epithelial antiproteases, e.g., secretory leukocyte protease inhibitor, may also increase locally 24 to 48 hr after elastase concentrations become excessive. Thus, the epithelium is not merely a passive barrier to ozone injury but has a dynamic role in directing the migration, activating, and then counteracting inflammatory cells. Through these complex interactions, epithelial cells can be viewed as the initiators (alpha) and the receptors (omega) of ozone-induced airway disease.

Airway Epithelial Cell Responses to Ozone Injury

The airway epithelial cells is an important target in ozone injury. Once activated, the airway epithelium responds in three phases. The initial, or immediate phase, involves activation of constitutive cells, often through direct covalent interactions including the formation of secondary ozonolysis products--hydroxyhydroperoxides, aldehydes, and hydrogen peroxide. Recently, we found hydroxyhydroperoxides to be potent agonists of bioactive eicosanoid formation by human airway epithelial cells in culture. Other probable immediate events include activation and inactivation of enzymes present on the epithelial surface (e.g., neutral endopeptidase). During the next 2 to 24 hr, or early phase, epithelial cells respond by synthesis and release of chemotactic factors, including chemokines--macrophage inflammatory protein-2, RANTES, and interleukin-8. Infiltrating leukocytes during this period also release elastase, an important agonist of epithelial cell mucus secretion and additional chemokine formation. The third (late) phase of ozone injury is characterized by eosinophil or monocyte infiltration. Cytokine expression leads to alteration of structural protein synthesis, with increases in fibronectin evident by in situ hybridization. Synthesis of epithelial antiproteases, e.g., secretory leukocyte protease inhibitor, may also increase locally 24 to 48 hr after elastase concentrations become excessive. Thus, the epithelium is not merely a passive barrier to ozone injury but has a dynamic role in directing the migration, activating, and then counteracting inflammatory cells. Through these complex interactions, epithelial cells can be viewed as the initiators (alpha) and the receptors (omega) of ozone-induced airway disease.

Ozonolysis of (cyclohexa-1,4-dienyl)-L-alanine. An approach to the synthesis of new unnatural amino acids. X-Ray molecular structure of 2-hydroxy-7-methyl-3-phenylpyrazolo[1,5-a]pyrimidine

The aromatic ring in L-phenylalanine was transformed into isoxazolyl, N-phenylpyrazolyl, and the bicyclic pyrazolo[1,5-a]pyrimidinyl groups, by a combination of Birch reduction and ozonolysis, followed by condensation with the relevant binucleophiles. The ozonolysis was carried out on the N-acylated esters of cyclohexa-1,4-dienylalanine. The resulting N-acylated esters of heterocyclic alanine derivatives were obtained without isolation of the ozonolysis products. 4-Phenylpyrazolidine-3,5-dione was used as a ‘hydrazine donor’ in the construction of a pyrazolyl group, as direct condensation with hydrazine was successful.

Transformation of solvent-derived ozonolysis products to bicyclic peroxides: Isolation and characterisation of novel pentoxonane derivatives

α-Hydroperoxyisochroman derivatives 5 react with formaldehyde under acidic conditions to produce mixtures of bicyclic 1,2,4,6-tetroxepane 9 and 1,2,4,6,8-pentoxonane 10 derivatives. The structure of the compound 10a was unambiguously established by the X-ray analysis. With acetaldehyde, only the corresponding 1,2,4,6-tetroxepanes 9 were obtained.

Bile salts of the toad, Bufo marinus: characterization of a new unsaturated higher bile acid, 3 alpha,7 alpha,12 alpha,26-tetrahydroxy-5 beta-cholest-23-en-27-oic acid.

The bile salts present in gallbladder bile of the toad, Bufo marinus, were found to consist of a mixture of bile alcohol sulfates and unconjugated bile acids. The major bile alcohol was 5 beta-bufol; 5 alpha- and 5 beta-cholestane-3 alpha,7 alpha,12 alpha, 26-tetrols occurred as the minor bile alcohols. Bile acids of Bufo marinus were cholic acid, allocholic acid, 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha- and 5 beta-cholestan-26-oic acids, 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha- and 5 beta-cholest-23-en-26-oic acids, 3 alpha,7 alpha,12 alpha, 26-tetrahydroxy-5 beta-cholestan-27-oic acid, and a C27 bile acid which has not been previously described. By chromatographic behavior, mass spectral data, and identification of the products of catalytic hydrogenation and ozonolysis, the structure of the new higher bile acid was elucidated as 3 alpha,7 alpha,12 alpha,26-tetrahydroxy-5 beta-cholest-23-en-27-oic acid. The bile salt pattern of Bufo marinus closely resembles that of Bufo vulgaris formosus, except for the absence of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-22-ene-24-carboxylic acid, the major bile acid of the latter toad.

Specific Immunization Using Keyhole Limpet Hemocyanin-Ganglioside Conjugates1

In a search for adjuvants of non-bacterial origin for immunization with ganglioside, we investigated whether chemical coupling to immune stimulatory protein could increase the immunogenicity of sialoglycosphingolipid. A novel method for the linkage of glycosphingolipids, including gangliosides, to protein was established. The procedure includes lysis of the sphingoid double bond by ozone, reduction of the ozonolysis product to the aldehyde, and coupling to amino groups, either directly by reductamination, or by conjugation via a long aliphatic chain dicarboxylic acid linker. Using this method, gangliosides Gfpt1 (IV2-Fuc-, II3NeuAc-Gg4Cer), Glac2 [II3(NeuAc)2-LacCer], and Gtet1 (II3NeuAc-Gg4Cer) were coupled to keyhole limpet hemocyanin (KLH), and the immunogenicity of the conjugates was tested. Immunization of mice with the KLH-ganglioside conjugates led in each case to the formation of IgG- and IgM antibodies that recognized the underivatized gangliosides, respectively. In contrast to this, mixtures of KLH and ganglioside proved ineffective for immunization. KLH-tumor-associated ganglioside conjugates may, therefore, be considered as possible vaccines in immune therapy of cancer.