Epoxides, identification

A careful analysis of this problem led to the identification of an exceedingly simple solution (see Scheme 10). The Masamune-Sharpless solution to the threo 2,3-diol problem actually takes advantage of the ready availability of the erythro 2,3-diol diastereoisomer. As we have seen in Scheme 9, erythro 2,3-diols such as 20 can be conveniently assembled from trans allylic alcohols via sequential SAE and Payne rearrangement/epoxide opening reac-... 

Britton, G., UV/visible spectroscopy, in Carotenoids Spectroscopy, IB, Britton, G., Liaaen-Jensen, S., and Pfander, H., Eds., Birkhanser, Basel, 1995, 13. Melendez-Martinez, A.J. et ah. Identification of isolntein (Intein epoxide) as cis-antheraxanthin in orange juice, J. Agric. Food Chem., 53, 9369, 2005. 

Currently there are four major lines of approach towards gas-phase epoxidation of propylene (1) mechanistic studies of Au/Ti02 catalysts through kinetics, spectroscopic identification of adsorbed species and... 

The identification of surface adsorbed species has been carried out with FT-IR [69] and Raman spectroscopy [70] during reaction and with GC-MS after epoxidation reaction [72]. The aggregation of gold NPs is not appreciable during reaction at temperatures below 473 K [69,72]. Catalyst deactivation, which happens within a few hours causing a decrease in C3FI6 conversion by about 50%, can be accounted for by the accumulation of successively oxidized compounds after isomerization and cracking of... 

Labeque, R. and Marnett, L.J. (1988). 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-dihydrobenzo [a]pyrene. Biochemistry 27, 7060-7070. 

Research in PAH carcinogenesis has made major advances in the past decade. Most notable has been identification of diol epoxide metabolites as the active forms of benzo[a]pyrene, 7,12-dimethylbenz[tf]anthracene, and other carcinogenic PAH. This finding has stimulated enormous research activity and opened the way to determination of the detailed molecular mechanism of action of this important class of carcinogenic molecules. 

Recent advances in PAH carcinogenesis research over the past decade have led to identification of diol epoxide metabolites as the principal active forms of the PAH investigated to date Q,2). Benzo-(a)pyrene (BP) has been most intensively investigated, and it has been demonstrated that a diol epoxide metabolite anti-BPDE is the active intermediate which binds covalently to DNA in human and other mammalian tissues 0,4). Anti-BPDE was also demonstrated to be a powerful mutagen in both bacterial and mammalian cells (15) These findings stimulated an outpouring of research directed towards elucidation of the molecular mechanism of PAH carcinogenesis. 

Studies on the comparative abilities (13) of B[a]P metabolites to bind to DNA in microsomal systems showed that the 7,8-dihydrodiol was the most efficient. This led to the proposal (69) that dihydrodiol epoxides were the ultimate carcinogenic metabolites. Chemical synthesis of all possible isomers (70.71) has allowed complete structural identification of the adducts (72-74). 

Various approaches to epoxide also show promise for the preparation of chiral aziridines. Identification of the Cu(I) complex as the most effective catalyst for this process has raised the possibility that aziridination might share fundamental mechanistic features with olefin cyclopropanation.115 Similar to cyclo-propanation, in which the generally accepted mechanism involves a discrete Cu-carbenoid intermediate, copper-catalyzed aziridation might proceed via a discrete Cu-nitrenoid intermediate as well. 

If the tetra- and tripodal Ti structures and the titanium oxo species derived from these structures in the presence of ROOH (R = H, alkyl) are involved as active sites and reaction intermediates, the next step beyond their identification is to seek correlations between the structure and concentrations of these titanium oxo species and catalytic activity and selectivity. Clerici and Ingallina (204) were the first to propose the Ti(02H) group as the active site of alkene epoxidation by... 

This is not the first time that the kinetics of bulk polymerizations has been analysed critically. Szwarc (1978) has made the same objection to the identification of the rate constant for the chemically initiated bulk polymerization of tetrahydrofuran as a second-order rate constant, k, and he related the correct, unimolecular, rate constant to the reported by an equation identical to (3.2). Strangely, this fundamental revaluation of kinetic data was dismissed in three lines in a major review (Penczek et al. 1980). Evidently, it is likely to be relevant to all rate constants for cationic bulk polymerizations, e.g., those of trioxan, lactams, epoxides, etc. Because of its general importance I will refer to this insight as Szwarc s correction and to (3.2) as Szwarc s equation . 

Fig. 2.3. Characteristic chromatogram of paprika paste. Detection at 450 nm. Peak identification 1 = Capsorubin 2 = 5,6-Diepikarpoxanthin 3 = Capsanthin-5,6-epoxide 4 = Capsanthin-3,6-epox-ide 5 = Violaxanthin 6 = Luteoxanthin 2 7 = Luteoxanthin 1 8 = Capsanthin 9 = Antheraxanthin 10 = Mutatoxanthin 11 = Cucurbitaxanthin A 12 = (9/9 Z)-Capsanthins 13 = (13/13 Z)-Capsanthins 14 = Zeaxanthin 15 = Nigroxanthin 16 = (9Z)-Zeaxanthin 17 = (13Z)-Zeaxanthin 18 = Cryptocapsin 19 = a-Cryptoxanthin 20 = /TCryptoxanthin 21 = (Z)-Cryptoxanthin 22 = /1-Carotene 23 = (Z)-jS-Carotene. Reprinted with permission from J. Deli et al. [27].

Fig. 2.16. HPLC profile of carotenoids in an extract of vegetable soup. An expansion of the profile from 30 to 39 is shown in the inset (A). Monitored wavelengths were 436, 440, 464, and 409 nm for peaks 9,10,11,12, and 14, respectively, in the inset (A). Peak identification 1 + 1" = all-trans-lutein and cw-lutein 2 = 5,6-dihydroxy-5,6-dihydrolycopene (lycopene-5,6-diol) 3 = j3-apo-8 -carotenal (internal standard) 4 = lycopene 1,2-epoxide 5 = lycopene 5,6-epoxide 6 = 1,2-dimethoxyproly-copene (tentative identification) 7 = 5,6-dimethoxy-5,6-dihydrolycopene 8 = lycopene 9 = pheo-phytin b 10 = neurosporene 11 = (-carotene 12 = pheophytin a 13 = (-carotene 14 = pheophytin a isomer and (-carotene 15 = a-carotene 16 and 16" = all-trans-/fcarotene, cis-/J-carotene 17 and 17" = all-trans- or cA-phytofluene 18 and 18" = all-trans- or cw-phytoene. Reprinted with permisson from L. H. Tonucci et al. [40].

A critical input in unraveling the catalytic mechanism of epoxide hydrolases has come from the identification of essential residues by a variety of techniques such as analysis of amino acid sequence relationships with other hydrolases, functional studies of site-directed mutated enzymes, and X-ray protein crystallography (e.g., [48][53][68 - 74]). As schematized in Fig. 10.6, the reaction mechanism of microsomal EH and cytosolic EH involves a catalytic triad consisting of a nucleophile, a general base, and a charge relay acid, in close analogy to many other hydrolases (see Chapt. 3). 

A. Harsch, J. M. Sayer, D. M. Jerina, P. Vouros, HPLC-MS/MS Identification of the Positionally Isomeric Benzo[c]phenanthrene Diol Epoxide Adducts in Duplex DNA , Chem. Res. Toxicol. 2000, 13, 1342 - 1348. 

Following oral or intraperitoneal administration of heptachlor or heptachlor epoxide to male mice that were then bred with untreated females, the preimplantation losses and resorptions were within control limits (Arnold et al. 1977 Epstein et al. 1972). However, lack of corpora lutea counts may have resulted in inaccurate identification of preimplantation losses. On the other hand, when both sexes of mice or rats were fed diets containing heptachlor in multigeneration studies, resorptions were increased relative to controls, and fertility was markedly decreased (Green 1970), in some instances to zero (Akay and Alp 1981). These results seem to suggest that heptachlor affects the female reproductive system and/or the fetuses and may also affect the male reproductive system. 

Intermediate-Duration Exposure. Because the human studies do not report quantitative information on dose or duration, it is not possible to know with certainty whether the combined inhalation and dermal exposures were of intermediate duration. There are intermediate-duration oral exposure data from animal studies that indicate that the liver and the hematologic systems are affected by heptachlor exposure (Enan et al. 1982 Halacka et al. 1974 Pelican 1971). The liver is probably the more sensitive of the two. No intermediate-duration oral or inhalation MRLs for heptachlor or heptachlor epoxide have been determined because of limitations in the studies, including lack of statistical comparisons, insufficient number of dose levels, no identification of NOAELs, and the description of effects that may be considered adaptive and not adverse. 

Analytical methods exist for measuring heptachlor, heptachlor epoxide, and/or their metabolites in various tissues (including adipose tissue), blood, human milk, urine, and feces. The common method used is gas chromatography (GC) coupled with electron capture detection (ECD) followed by identification using GC/mass spectrometry (MS). Since evidence indicates that heptachlor is metabolized to heptachlor epoxide in mammals, exposure to heptachlor is usually measured by determining levels of heptachlor epoxide in biological media. A summary of the detection methods used for various biological media is presented in Table 6-1. 

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