Diene hydroperoxides

Autoxida.tlon. The autoxidation (7) of unsaturated fatty acids in phosphoHpids is similar to that of free acids. Primary products are diene hydroperoxides formed in a free-radical process. 

In bronchitics, there have been reports of elevated serum-conjugated dienes, hydroperoxides and aldehydes, and a claim of clinical eflicacy as well as normalization of these parameters after vitamin E therapy (Kleiner et al., 1990). However, these patients were given combined therapy including steroids and thus the effect of vitamin E alone cannot be assessed. N-Acetylcysteine administered to chronic bronchitics increased plasma cysteine from a below-normal baseline but it has not been shown that this intervention had any effect on the disease process, the dosing being of short duration, nor were there short-term effects of the release of ROS from blood neutrophils (reviewed by MacNee et al., 1991). A... 

Molecular species (hydroperoxide combination) Molar ratio (weight conjugated diene hydroperoxide phosphate)... 

In 1990, Triantaphylidds and coworkers reported on the preparative enzymatic synthesis of hnoleic acid (135) hydroperoxide 24a using soybean lipoxygenase-1. In this dioxygenation asymmetry is induced by the catalyst, the enzyme. The reaction was later used by Dussault and also by Baba and coworkers as key step in the preparation of more complex peroxides. The enzyme is a non-heme iron dioxygenase which catalyzes the incorporation of dioxygen into polyunsaturated fatty acids to yield E,Z conjugated diene hydroperoxides 24a-d. With this enzymatic method, the hydroperoxide 24a could... 

Figure C4.2.1 Lipoxygenase (LOX)-catalyzed transformation of linoleic or linolenic acid (R = CH3(CH2)4-, linoleic acid R = CH3CH2CH=CHCH2-, linolenic acid) showing oxidation by molecular oxygen and formation of conjugated diene hydroperoxides. These events give the basis for measurement of activity by either oxygen uptake or UV absorption at 234 nm. Also shown is the usual preference for (S)-stereospecificity of oxidation.

E,E)-diene hydroperoxides and do not require CP-HPLC analysis. All four peaks are integrated to obtain the percent regiocomposition. 

Polar cyclization of diene hydroperoxide 304 has been successfully effected by Hg(NC>3 )2 to produce a 2 1 mixture of 1,2-dioxolane 305 and 1,2-dioxane 306. In contrast, a radical cyclization with (Bu CX)(. ())2 and O2 or /V-iodosuccinirnidc, respectively, is more selective giving only one 1,2-dioxane425. 

Vitamin E is effective as an antioxidant in arachidonate autoxidation, trapping the kinetic peroxyl radical product before cyclization can occur. Adding vitamin E in arachidonate autoxidation results in reducing radical cyclization products and forming the kinetic product distribution, six simple trans, cis diene hydroperoxides. 

These peroxyl radicals then attack another molecule of linoleic acid to abstract an allylic hydrogen and produce the conjugated diene hydroperoxide, LOOH, Equation 7. 

Lipoxygenases. Lipoxygenases catalyze the peroxidation of polyunsaturated fatty acids with a cis.cis 1-4-pentadiene moiety to form conjugated diene hydroperoxides (Figure lc). Free fatty acids are formed following wounding from the deacylation of membrane... 

Lipoxygenase (leukocytes) Fe(III)(His)4 (PQQ )(02), Ca(II) 1,4-diene1,3-diene hydroperoxide Antiinflammatory, antihypersensitivity agents (acetohy-droxamates)... 

Lipoxygenase enzymes are known to oxidize arachidonic acid at six possible positions. The chemical requirement for this oxidation (Eq. 4.1) appears simply to be a skipped cis diene which can produce (via the enzyme) a stabilized allylic radical, which then traps molecular oxygen to form a conjugated cis-trans diene hydroperoxide. Chart 4.1 shows the six possible mono-oxidation products as members of the HETE family. All of these compounds have been shown to be natural products. Only in the cases of 8 and 9 HETEs is the absolute stereochemistry not definitively known. Nevertheless, it is speculated that 8-HETE has the alcohol in the (5)-configuration and 9-HETE is of the (R) absolute... 

Conjugated diene hydroperoxides produced from polyunsaturated lipids can be determined quantitatively by their strong absorption at 234 nm. This sensitive method can only apply to undegraded hydroperoxides. 

Stereochemical studies based on HPLC and C-NMR (Chapter 6) showed the formation of a mixture of four cis,trans and trans,trans conjugated diene hydroperoxides ... 

The conjugated diene hydroperoxides produced from polyunsaturated lipids can be determined quantitatively by their strong absorption maximum at 234 nm (molecular extinction of 25,000-29000 for a solution of 1 mole hydroperoxides/1 methanol). A weighed sample is simply diluted in methanol (for esters) or in isooctane (for triacylglycerols) and the absorbance at 234 nm measured spectrophotometrically. Aqueous emulsions can also be measured directly by dissolving in methanol even if the solutions becomes slightly cloudy, provided a suitable blank is used with the same diluted unoxidized sample. The conjugated diene value of lipids can be determined by their UV absorbance at 234 nm and expressed in /imol hydroperoxides/g sample. 

Lipoxygenase (EC 1.13.11.12) catalyses the stereospecific dioxygenation of polyunsaturated fatty acids containing a l,4-cis,cis-pentadiene system to a pentadienyl radical intermediate which reacts with molecular oxygen to yield ris,trans-conjugated diene hydroperoxides (Wiseman et al. 1988). 

Rapeseed phenolics isolated by Vuorela et al. (2004) were tested for radical scavenging and for liposome and low-density lipoprotein (LDL) model systems. The inhibition of hexanal and conjugated diene hydroperoxides formation was reported (>90% and >80%, respectively). All isolates also exhibited inhibition of LDL particles oxidation by >90%. The antioxidant activity of methanol and acetone extracts of canola hulls in a P-carotene-linoleate model system was comparable to that displayed by butylated hydroxyanisole (Naczk et al., 2005). These extracts showed more than 95% scavenging effects (at 40 p/assay on DPPH radical). Vuorela et al. (2005a,b) indicated that rapeseed phenolics were excellent antioxidants towards oxidation of phosphatidylcholine membrane (liposomes) and rapeseed oil (crude) phenolics were effective radical scavengers (DPPH test). The authors suggested that these phenolic isolates from rapeseed are safe and bioactive for possible food applications including functional foods intended for health benefit. 

As a model substrate, 2,5-dimethyl-2,4-hexadiene 51 has been intensively investigated by several research groups. Depending on the solvent polarity, hve peroxidic products have been isolated in varying relative yields the endoperoxide 52 (from [4 + 2]-cycloaddition), the aUylic hydroperoxide 53 (from ene reaction), the 1,2-dioxetane 54 (from [2 + 2]-cycloaddition), the diene hydroperoxide 55 (either from a vinylogous ene reaction or a radical-induced rearrangement of 53), and the methoxy-substituted hydroperoxide 56 (a methanol trapping product) were observed. A maximum of 23% of the [4 -I- 2]-cycloaddition product 52 was detected in tetrachloromethane, whereas the dioxetane 54 dominated in polar acetonitrile. 

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