Arachidonic acid methyl ester

Conversion of bromohydrins to alkenes. The 14,15-epoxide (1) of arachidonic acid methyl ester has been converted into the 11,12-epoxide (5) in two steps. The first is conversion of 1 into a mixture of isomeric bromohydrins (2 and 3) with KBr. The mixture is then epoxidized under the conditions of Sharplcss (5, 75 76) to give, after chromatographic purification, 4, the epoxide of 2. Conversion of 4 into 5 presented a problem, but was eventually achieved by treatment of the w c-bromo Inflate with P[N(CHj)2]j as a Br acceptor. 

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. 

Moghaddam et al. (13) reported that linoleic acid and arachidonic acid can be metabolized to their dihydroxy-THFA (tetrahydrofuran-diols) in vitro by microsomal cytochrome P450 epoxidations, followed by microsomal epoxide hydrolase. In their metabolic pathways, saturated dihydroxy-THFA are produced because 9,10(12,13)-dihydroxy-12,13(9,10)-epoxy-octadecanoate converted from linoleic acid methyl ester are cyclized (13). These saturated dihydroxy-THFA exhibit cytotoxic activity and mitogenic activity for breast cancer and... 

Figure 6 A typical gas-liquid chromatogram of total bovine milk FAME prepared by NaOCHsfmethanol (10 min at SO C) followed by HCI/methanol (10 min at 80°C), and separated on a 100 m fused silica capillary column (SP-2560) Supelco Inc., Bellefonte, PA). I, iso a, anteiso numbers 1-20 are arbitrary consecutive numbering of all peaks in the region between 18 0 and 18 2o6 using this column. (22 6/>3) is not present in these milk samples but the position at which it should emerge in the chromatogram is indicated. Insert the methyl eicosanoate (20 0) to methyl arachidonate (20 4/>6) region of the GLC of total bovine fatty acid methyl esters prepared by using conventional catalysts. Reproduced with permission from Kramer JKG, Fellner V, Dugan MER, Sauer FD, Mossoba MM, and Yurawecz MP (1997) Lipids 32 1219-1228.

These GC conditions are suitable for analyzing many prostaglandins, thromboxanes, leuko-trienes, and other metabolites of arachidonic acid, such as the hydroxyeicosatetraenoic (HETE) acids. However, the 5-, 12-, and 15-HETE isomers are difficult to separate using GC methods. Sometimes the methyl ester-TMS derivatives provide a better GC separation, or for ketoprostaglandins, the MO-methyl ester-TMS derivatives often give a better separation... 

Methyl and other alkyl esters were prepared in THF, also in high yields.[130] b) Arachidonic acid was converted via its tetrazolide with the aid of oxalyldi(l,2,3,4-tetrazole), prepared in situ, into the methyl ester.[1113... 

Resolution of alcohols (cf., l-(naphthyl)cthyl isocyanate, 8, 356 357). A practical synthesis of the methyl ester of (S)-5-HF,TF. (1) from arachidonic acid involves chromatographic separation of the diastereomeric urethanes preparecT from the Isocyanate derived from dehydroabietylamine (hydrogen chloride and phosgene).1 Urethanes from other chiral amines are less useful. The urethanes are cleaved with triethylamine and trichlorosilanc to give the corresponding pure enantiomeric esters, which can be hydrolyzed by base. 

The substrate arachidonic aeid, whieh often leads to formation of inflammatory prostaglandins, is stored in tissues as one of a number of phospholipids these compounds, as the name indicates, comprise complex phosphate-containing esters. The antiinflammatory corticosteroids inhibit the action of the enzyme, phospholipase A2, that frees arachidonic acid. The many undesired effects of those steroids has led to the search for non-steroidal inhibitors of that enzyme. A highly substituted indole derivative has shown good activity as a phospholipase A2 inhibitor. Alkylation of the anion from treatment of indole (32) with benzyl chloride affords the corresponding A-benzylated derivative (33). The methyl ether at the 4 position is then cleaved by means of boron tribromide to yield 34. Alkylation of the enolate from reaction of the phenol with sodium hydride with tert-butylbromoacetate affords the corresponding... 

The benzofuran epoxides 70 are found to be the most reactive epoxides functioning as alkylative agents. Polyunsaturated free fatty acids, namely linoleic, arachidonic, and eicosatrienic acids, and also their methyl esters have been epoxidized using lb <2006HCA2243>. When the reaction is performed in water, it has been found that due to supramolecular organization of fatty acids into a micelle, the C=C bonds closest to the aqueous-micelle interface are most prone to epoxidation. 

Beltramo et al. 1997). Arachidonamide and arachidonic acid esters (methyl, ethyl, propyl) do not show significant affinity for CBi (Sheskin et al. 1997), while cyclization of the head group into an oxazoline ring diminishes affinity (Lin et al. 1998). 

Three 4-thiazolidinone libraries were prepared and assayed for inhibition of the enzyme cyclooxygenase-1 (COX-1), a key enzyme in the conversion of arachidonic acid to prostaglandins [421, 422], From the carboxylic acid, ester and carboxamides libraries only the methyl ester library showed significant activity. A series of three rounds of testing and deconvolution led to a compound (library 37 IC50 3.7 fiM) with equivalent in vitro activity to the commercially available COX-1 inhibitors ibuprofen and phenylbutazone. 

Anandamide and its head-group-modihed analogs (70-72, Fig. 9) were prepared by reaction of the appropriate amino alcohols or aminophenols with arachidonic acid chloride. Alternatively, direct transformation of the methyl ester of arachidonic acid to the corresponding amides was achieved by cyanide-catalyzed amidation (84). 

The synthesis of a novel cyclopropyl analog of arachidonic acid [7] via a convergent synthesis that employed methyl (lR,25)-2-formylcyclopropane-carboxylate in conjunction with the ylide from (3Z,6Z)-pentadeca-3,6-dienyl(triphenyl)-phosphonium iodide was reported (62). A new approach to cyclopropene fatty acids has been developed for the synthesis of methyl sterculate [8] and methyl 2-hydroxy-sterculate this involves the 1,2-deiodination of 1,2-diiodocyclopropanes with butyllithium at low temperature (63). The synthesis of deuterated cyclopropene fatty esters structurally related to palmitic and myristic acids has been reported (64). 

Of relevance to this class of derivatives is t-butyl-methoxyphenylbromosilane (TBMPSBr 42), which was originally developed as a versatile and selective protecting group for alcohols that was stable to hydrolysis [440]. Ainong the few known analytical applications is its use in the GC-MS analysis of the arachidonic acid metabolite 12,20-dihydroxyeicosatetraenoic acid (12,20-diHETE) as the methyl ester 12-TMS, 20-TBMPS ether [441]. A more recent application was aimed at... 

Arachidonic acid is obtained from pig liver lipid by distillation of the methyl esters after chromatographic removal of cholesterol, followed by urea fractionation and silver ion chromatography. 

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