Arachidonic configuration

Arabinose, configuration of. 982 Kiliani-Fischer synthesis on. 995 Arachidic acid, structure of, 1062 Arachidonic acid, eicosanoids from, 1069-1070... 

Capdevila, J.A., Yadagiri, P., Manna, S. and Falck, J.R. (1986). Absolute configuration of the hydroxyeicosatetraenoic acids (HETEs) formed during catalytic oxygenation of arachidonic acid by microsomal cytochrome P-450. Biochem. Biophys. Res. Commun. 141, 1007-1011. 

Nomenclature Fatty acids are named according to the number of carbon atoms in the chain and the number and position of any double bonds. Some of the more common fatty acids are palmitate (06 0), stearate (08 0), oleate (08 1), linoleate (08 2), linolenate (08 3) and arachidonate (C20 4). The double bonds in a fatty acid are usually in the cis configuration. 

This strategy to prepare rran.r,as-configurated functionalized dienes like 34 has elegantly been exploited for syntheses of HETEs (hydroxyeicosatetraenoic acids) and leukotrienes 27). These metabolites of arachidonic acid have received much attention due to thek biological activity. Syntheses of HETEs, for instance, follow the principle outlined in Eq. 12 with the acid catalysed ring opening of homofuran derivatives 36 to 37 as the stereoselective key step. 

Dehydroabietyl isocyanate, [39], was used by Falck et al. to determine the absolute configuration of hydroxyeicosatetraenoic acid methyl esters in a study of the enzymatic epoxidahon of arachidonic acid (175). In another study of similar metabolites, the stereochemical identity of 12-hydroxy-5,8,10,14-eicosatetraenoic acid derived from the lesional scale of patients with psoriasis was studied via separation of the enantiomers after derivatization with [39] (176). In these studies (175,176), LC separation of the derivatives was used. CDA [39] can be prepared from commercially available resolved dehydroabietylamine. It would be worthwhile to examine the applicability of this CDA to the resolution of other compounds. 

The fatty acid residues have usually even number of carbon atoms in the chains, ranging from 14 to 24 carbons and the double bond, if present, assumes the cis configuration. The phospholipids of animal origin comprise mainly palmitic oleic, linoleic and arachidonic fatty acids, while the ones of plant origin ones have mainly palmitic, oleic and linoleic tatty acids. 

Almost all naturally (Kcurring, unsaturated, long-chain fatty acids exist as the cis isomers, which are less stable than the trans isomers. The cis configuration introduces a bend (of about 30°) in the molecule, whereas the trans isomer resembles the extended form of the saturated chain (Figure 18-16). Arachidonic acid with four cis double bonds is a U-shaped molecule. Some cis isomers are biologically active as essential fatty acids. The trans isomers cannot substitute for them but are metabolized like the saturated fatty acids. 

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... 

A. Classification The principal eicosanoid subgroups are the prostaglandins, prostacyclin, thromboxanes, and leukotrienes. Prostacyclin and thromboxane are often considered members of the prostaglandin group since they are also cyclized derivatives. The leukotrienes retain the straight chain configuration of arachidonic acid. There are several series for most of the princi-... 

C) 15 position of arachidonic acid, predominantly in the 5 configuration (see fig. 2). This pathway implicated the involvement of the human 15-LO in the generation of bioactive molecules [56], and was of interest not only because... 

Previously, the strain DS5 bioconversion products from oleic and linoleic acids were identified as 10-ketostearic (23) and 10-hydroxy-12(Z)-octadecenoic acid(24), respectively. It is interesting to find that all unsaturated fatty acids tested are hydrated at the 9,10 positions with the oxygen functionality at C-10 despite their varying degree of unsaturations. DS5 hydratase was not active on saturated fatty acids and other non-9(Z)-unsaturated fatty acids such as elaidic [9(.B)-octadecenoic], arachidonic [5( ),8( ),1 l( ),14( )-eicosatetraenoic], and erucic [13( )-docosenoic] acids (25). From all of the data gathered, it is concluded fliat DS5 hydratase is indeed a C-10 positional-specific enzyme. The fact that elaidic acid was not hydrated indicates that die unsaturation must be in flie cis configuration for DS5 hydratase activity. 

Fig. 10. Summary of the enzymatic metabolism of arachidonic acid by cytochrome AaSO. The epoxides presumably all have the as configuration although this has only been shown for the w6 oxide. The epoxides are hydrolysed by epoxide hydrolase into the vicinal diols. Arachidonic acid and the vicinal diols may be further metabolised by wl- and w2-hydroxylation.

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