Competitive Epoxidation Research Articles

17Beta-estradiol epoxidation as the molecular basis for breast cancer initiation and prevention.

Epidemiological and animal studies have indicated that 17beta-estradiol (E2) is involved in breast cancer; however, the mechanism is unclear. We found that E2 could be activated by epoxidation, resulting in its ability to inhibit nuclear DNA-dependent RNA synthesis, and to bind DNA, forming DNA adducts both in vitro and in vivo. Because epoxidation is required for the activation of many chemical carcinogens, including benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene and aflatoxins, we proposed previously that E2 epoxidation is the underlying mechanism for the initiation of breast cancer. The first part of this review is to present the experimental evidence obtained from this laboratory in support of this hypothesis. Based on these newly discovered insights on E2 epoxidation and its initiation role in breast cancer carcinogenesis, a method to screen chemopreventive agents against breast cancer has been developed. This constitutes the second part of the review. Two examples will be used to illustrate the utility of this screening technique. The effect of fat on breast cancer has been a longstanding but unresolved issue. Epidemiological studies provide conflicting results regarding the association of dietary fat and breast cancer. Because vegetable oils contain various amount of mono- and polyunsaturated fatty acids, they are potential antioxidants. Data are presented to show that commercial vegetable oils, independent of their mono- or polyunsaturated fatty acid content, are all able to prevent the formation of E2 epoxide, as measured by the loss of the ability of E2 to inhibit nuclear RNA synthesis in vitro. Tamoxifen (TAM), an anti-estrogen used for breast cancer treatment, has recently been found to have a strong breast cancer preventive effect. The mechanism for this is unknown. Using the same screening technique, we found that when incubated together with E2 for epoxidation, TAM was able to prevent the formation of E2 epoxide, as evidenced by both the loss of the ability of E2 to inhibit nuclear RNA synthesis and the reduced binding of [3H]-labelled E2 to nuclear DNA in a dose-dependent manner. These experimental results suggest that the breast cancer preventive effect of TAM is to prevent the formation of E2 epoxide through a competitive epoxidation mechanism with E2.

Anionic ligand effect on the nature of epoxidizing intermediates in iron porphyrin complex-catalyzed epoxidation reactions.

We have studied an anionic ligand effect in iron porphyrin complex-catalyzed competitive epoxidations of cis- and trans-stilbenes by various terminal oxidants and found that the ratios of cis- to trans-stilbene oxide products formed in competitive epoxidations were markedly dependent on the ligating nature of the anionic ligands. The ratios of cis- to trans-stilbene oxides obtained in the reactions of Fe(TPP)X (TPP = meso-tetraphenylporphinato dianion and X(-) = anionic ligand) and iodosylbenzene (PhIO) were 14 and 0.9 when the X(-) of Fe(TPP)X was Cl(-) and CF(3)SO(3)(-), respectively. An anionic ligand effect was also observed in the reactions of an electron-deficient iron(III) porphyrin complex containing a number of different anionic ligands, Fe(TPFPP)X [TPFPP = meso-tetrakis(pentafluorophenyl)porphinato dianion and X(-) = anionic ligand], and various terminal oxidants such as PhIO, m-chloroperoxybenzoic acid (m-CPBA), tetrabutylammonium oxone (TBAO), and H(2)O(2). While high ratios of cis- to trans-stilbene oxides were obtained in the reactions of iron porphyrin catalysts containing ligating anionic ligands such as Cl(-) and OAc(-), the ratios of cis- to trans-stilbene oxide were low in the reactions of iron porphyrin complexes containing nonligating or weakly ligating anionic ligands such as SbF(6)(-), CF(3)SO(3)(-), and ClO(4)(-). When the anionic ligand was NO(3)(-), the product ratios were found to depend on terminal oxidants and olefin concentrations. We suggest that the dependence of the product ratios on the anionic ligands of iron(III) porphyrin catalysts is due to the involvement of different reactive species in olefin epoxidation reactions. That is, high-valent iron(IV) oxo porphyrin cation radicals are generated as a reactive species in the reactions of iron porphyrin catalysts containing nonligating or weakly ligating anionic ligands such as SbF(6)(-), CF(3)SO(3)(-), and ClO(4)(-), whereas oxidant-iron(III) porphyrin complexes are the reactive intermediates in the reactions of iron porphyrin catalysts containing ligating anionic ligands such as Cl(-) and OAc(-).

Evidence for parallel destructive, and competitive epoxidation and dismutation pathways in metalloporphyrin-catalysed alkene oxidation by hydrogen peroxide

A kinetic and product yield analysis of the F 20TPPFeCl-catalysed H 2O 2 epoxidation of cyclooctene has shown that decomposition is not via either the oxoperferryl intermediate (F 20TPP + )Fe IVO or the oxoferryl intermediate F 20TPPFe IVO, but appears to involve direct oxidation of the porphyrin in parallel with the catalytic epoxidation cycle. This is in contrast to the reaction of F 20TPPFeCl in the absence of alkene where decomposition is via F 20TPPFe IVO.

The mechanism of tamoxifen in breast cancer prevention

Tamoxifen (TAM) is known to have a dual mechanism of action: (1) to compete with 17β-estradiol (E2) at the receptor site and to block the promotional role of E2 in breast cancer; and (2) to bind DNA after metabolic activation and to initiate carcinogenesis. Recent large clinical trials indicate that TAM is also an effective chemopreventive agent against breast cancer. The mechanism is unknown. Because E2 requires activation by epoxidation to bind DNA forming DNA adducts [1], and the same is true for TAM [2], the question is whether this preventive effect of TAM against breast cancer is contributory to the possibility that TAM, as an effective competitor for epoxidation, prevents the formation of E2 epoxide and consequently breast cancer. Evidence will be presented to show that, indeed, when incubated together with E2 for epoxidation, TAM was able to dramatically reduce the formation of E2 epoxide as measured by both the loss of the ability of E2 to inhibit nuclear RNA synthesis, and the reduced binding of [3H]labeled E2 to nuclear DNA. Identical results were obtained when TAM and estrone (E1) were used. These results suggest that the breast cancer preventive effect of TAM is through a competitive epoxidation mechanism with E1/E2.

Evidence for the Participation of Two Distinct Reactive Intermediates in Iron(III) Porphyrin Complex-Catalyzed Epoxidation Reactions

We have studied the competitive epoxidations of olefins with cis- and trans-stilbenes and with cyclooctene and trans-stilbene in iron porphyrin complex-catalyzed epoxidation reactions by H2O2, tert-butyl hydroperoxide (t-BuOOH), and m-chloroperoxybenzoic acid (m-CPBA) in protic solvent (i.e., a solvent mixture of CH3OH and CH2Cl2) and aprotic solvent (i.e., a solvent mixture of CH3CN and CH2Cl2) at room temperature under catalytic reaction conditions. The competitive epoxidations were also carried out with in situ generated high-valent iron(IV) oxo porphyrin cation radical complexes in aprotic solvent under stoichiometric reaction conditions. By determining the ratios of epoxide products formed in the competitive epoxidations, we were able to conclude unambiguously that the reactive species generated in protic solvent are high-valent iron(IV) oxo porphyrin cation radical complexes 3 and the intermediates formed in aprotic solvent are oxidant−iron porphyrin intermediates 2. A protic solvent such as methano...

Reactions of iron porphyrin complexes with hydroperoxides: Reactive intermediate, competitive epoxidation, and O-O bond cleavage

Reactions of iron porphyrin complexes with hydroperoxides: Reactive intermediate, competitive epoxidation, and O-O bond cleavage

Regio- and enantio-selective catalytic epoxidation of conjugated dienes

The regio- and enantio-selective catalytic epoxidation of conjugated aliphatic dienes have been studied using a variety of achiral and chiral manganese salen complexes and sodium hypochlorite or iodosylbenzene as the terminal oxidant. The catalysts show a preference for the less substituted alkene in most of the dienes studied, and in some cases a regioselectivity of 100% is found. The regioselectivity is dependent on the terminal oxidant applied. The enantiomeric excess (ee) obtained varies for the different conjugated dienes and the ee is generally highest for internal alkenes, where an ee of up to 71% is observed, whereas 48% is the highest observed ee for the less substituted alkenes. The ee is also dependent on the terminal oxidant applied. The regio- and enantio-selectivity have also been studied for different 1-(para-substituted phenyl)buta-1,3-dienes, but no regio- and enantio-selectivity dependence on the different substituents are observed. A competitive epoxidation experiment with styrene and 1-phenylbuta-1,3-diene shows that the latter is the most reactive and the difference in reactivity is discussed on the basis of the frontier orbitals of the two systems. The electronic structure of the oxo–manganese salen intermediate is investigated using INDO/1 calculations and it is found that the triplet state is the most stable state of the intermediate. Based on the electronic structure of the oxo–manganese salen intermediate a mechanism for the oxygen transfer step to the conjugated diene is proposed.

ChemInform Abstract: Competitive Epoxidation and Quinone Formation in the Dimethyldioxirane Oxidation of Diazoquinones as Ambident Nucleophiles.

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Competitive epoxidation and quinone formation in the dimethyldioxirane oxidation of diazoquinones as ambident nucleophiles

In addition to the expected dimethyldioxirane (DMD) oxidation of diazoquinones 1 to their quinones 2, the corresponding epoxy quinones 3 are formed directly and not as secondary overoxidation products of the quinones 2 since the latter are persistent towards DMD under these conditions; this novel oxidation is rationalized in terms of the ambident nucleophilic nature of the diazoquinones and corroborated by MO (AM1) calculations.

The selectivities and the mechanism on highly efficient epoxidation of olefins with 2,6-disubstituted pyridine N-oxides catalyzed by ruthenium porphyrin

Several remarkable selectivities in competitive epoxidations using a ruthenium porphyrin/ 2,6-disubstittuted pyridine N-oxide system were observed. The proposl that the active intermediate of this system differed from the trans-dioxo complex of ruthenium porphyrin was indicated.

Remarkable solvent effect on the shape-selective oxidation of olefins catalyzed by iron(III) porphyrins

The competitive epoxidation of norbornylene and alpha-methylstyrene by m-CPBA(m-CPBA = m-chloroperbenzoic acid) in the presence of a catalytic amount of iron pporphyrins in CH{sub 2}Cl{sub 2} and toluene is reported herein. The epoxidation reaction was found to form norbornylene over alpha-methylstyrene in a 63% yield, and changing the axial ligand from chloride to hydroxide did not cause any appreciable changes in the catalytic activity or selectivity of the reaction. The very different shape selectivities noted in toluene and CH{sub 2}Cl{sub 2} can be attributed to the alternation of the reactive species of the iron porphyrins. Two types of active species are proposed for the epoxidation reaction when the peracid-iron(III) porphyrin system was used. 12 refs., 1 fig., 1 tab.

Synthesis, characterization and catalytic behaviour of thorium peroxo complexes

Stable peroxo complexes of thorium are formed which are unreactive as stoichiometric reagents but active as catalysts in the presence of tert-butylhydroperoxide, resulting in the formation of cyclohexenone and cyclohexenol in substantial yields together with cyclohexene oxide. Competitive epoxidation of cyclo-olefins suggests that coordination of olefins to the metal centre does not take place.

Oxymetallation. Part III. Competitive epoxidation during the hydridodemercuration of β-mercurated dialkyl peroxides with sodium borohydride

Download options Please wait... Article information DOI https://doi.org/10.1039/P19720002433 Article type Paper Download Citation J. Chem. Soc., Perkin Trans. 1, 1972, 2433-2438 BibTex EndNote MEDLINE ProCite ReferenceManager RefWorks RIS Permissions Request permissions Oxymetallation. Part III. Competitive epoxidation during the hydridodemercuration of β-mercurated dialkyl peroxides with sodium borohydride A. J. Bloodworth and G. S. Bylina, J. Chem. Soc., Perkin Trans. 1, 1972, 2433 DOI: 10.1039/P19720002433 To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page. If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given. If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page. Read more about how to correctly acknowledge RSC content. Search articles by author A. J. Bloodworth G. S. Bylina