70578-51-7Relevant articles and documents
COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic acids in activated human leukocytes
Tejera, Noemi,Boeglin, William E.,Suzuki, Takashi,Schneider, Claus
, p. 87 - 94 (2012/03/26)
Biosynthesis of 5,15-dihydroxyeicosatetraenoic acid (5,15-diHETE) in leukocytes involves consecutive oxygenation of arachidonic acid by 5-lipoxygenase (LOX) and 15-LOX in either order. Here, we analyzed the contribution of cyclooxygenase (COX)-2 to the biosynthesis of 5,15-di-HETE and 5,11-diHETE in isolated human leukocytes activated with lipopolysaccharide and calcium ionophore A23187. Transformation of arachidonic acid was initiated by 5-LOX providing 5 S -HETE as a substrate for COX-2 forming 5 S,15 S -diHETE, 5 S,15 R -diHETE, and 5 S,11 R -di-HETE as shown by LC/MS and chiral phase HPLC analyses. The levels of 5,15-diHETE were 0.45 ± 0.2 ng/106 cells (mean ± SEM, n = 6), reaching about half the level of LTB 4 (1.3 ± 0.5 ng/106 cells, n = 6). The COX-2 specific inhibitor NS-398 reduced the levels of 5,15-diHETE to below 0.02 ng/106 cells in four of six samples. Similar reduction was achieved by MK-886, an inhibitor of 5-LOX activating protein but the above differences were not statistically significant. Aspirin treatment of the activated cells allowed formation of 5,15-diHETE (0.1 ± 0.05 ng/106 cells, n = 6) but, as expected, abolished formation of 5,11-diHETE. The mixture of activated cells also produced 5 S,12 S -diHETE with the unusual 6 E,8 Z,10 E double bond configuration, implicating biosynthesis by 5-LOX and 12-LOX activity rather than by hydrolysis of the leukotriene A 4 -epoxide. Exogenous octadeuterated 5 S -HETE and 15 S -HETE were converted to 5,15-diHETE, implicating that multiple oxygenation pathways of arachidonic acid occur in activated leukocytes. The contribution of COX-2 to the biosynthesis of dihydroxylated derivatives of arachidonic acid provides evidence for functional coupling with 5-LOX in activated human leukocytes. Copyright
Application of the low-valent titanium reductive elimination of 1,6-dibenzoate-2,4-dienes to the total synthesis of 6(E)-5(S)-12(R)-leukotriene B4
Solladie, Guy,Stone, Guy B.,Hamdouchi, Chafiq
, p. 1807 - 1810 (2007/10/02)
A stereoselective synthesis of 6(E)-5(S)-12(R)-leukotriene B4 is described in this paper, using a novel reaction, the low-valent titanium induced reductive elimination of a 1,6-dibenzoate-2,4-diene, for the selective synthesis of the trans-trie
Total synthesis of leukotriene (+)-LTB4 from D-mannitol
Le Merrer,Gravier,Languin-Micas,Depezay
, p. 4161 - 4164 (2007/10/02)
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