HETEs 15-HETE, synthesis from arachidonic

Resolution of alcohols (c/., l-(naphthyl)ethyl isocyanate, 8, 356-357). A practical synthesis of the methyl ester of (S)-5-HETE (1) from arachidonic acid involves chromatographic separation of the diastereomeric urethanes prepared" 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 trichlorosilane to give the corresponding pure enantiomeric esters, which can be hydrolyzed by base. 

Figure 7. Eicosanoid synthesis from arachidonic acid. COX, cyclooxygenase. HETE, hydroxyeicosatetraenoic acid. HPETE, hydroperoxyeicosatetraenoic acid. LOX, lipoxygenase. LT, leukotriene. LX, lipoxin. PG, prostaglandin. TX, thromboxane.

Figure 26-i I Synthesis of prostaglandins from arachidonic precursor. PG. Prostaglandin TX, thromboxane HPETE. HETE, HHT, l2-l-hydroxy-5,8, lO-heptadecatrienoic acid. 

HETE was the first product shown to arise from a lipoxygenase reaction of arachidonic acid in mammalian systems. Chronologically it was also the first lipoxygenase product to be synthesized. As outlined in Scheme 4.8, Corey et al. ° carried out a stereospecific total synthesis from acetonide alcohol 21 which... 

Monocyte-macrophages are the only principal cells of the immune system that can synthesize all the eicosanoids. T and B lymphocytes are interesting exceptions to the general rule that all nucleated cells produce eicosanoids. However, in a B lymphoma cell line, there is non-receptor-mediated uptake of LTB4 and 5-HETE. Interaction between lymphocytes and monocyte-macrophages may cause the lymphocytes to release arachidonic acid from their cell membranes. The arachidonic acid is then used by the monocyte-macrophages for eicosanoid synthesis. In addition to these cells, there is evidence for eicosanoid-mediated cell-cell interaction by platelets, erythrocytes, PMNs, and endothelial cells. 

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