89663-86-5

Usage

Biochem/physiol Actions

Lipoxin A4 (LXA4) is synthesized from arachidonic acid and is an endogenous lipoxygenase-derived eicosanoid mediator. It is a potent human protein kinase C activator. It inhibits cytotoxicity of natural killer cells. LXA4 regulates the immune system and inflammation. In the brain, it modulates neuronal signaling and slow wave sleep. LXA4 binds to cannabinoid receptors. LXA4 plays a key role in the maintenance of endometrium and reproductive function. Depletion of LXA4 contributes to the pathophysiology of cystic fibrosis (CF).

InChI:InChI=1/C20H32O5/c1-2-3-8-12-17(21)13-9-6-4-5-7-10-14-18(22)19(23)15-11-16-20(24)25/h4-7,9-10,13-14,17-19,21-23H,2-3,8,11-12,15-16H2,1H3,(H,24,25)/b6-4-,7-5+,13-9+,14-10+/t17-,18+,19-/m0/s1

Upstream product

• 94235-41-3 4-[(2S,3S)-3-((1E,3E,5Z,7E)-(S)-9-Hydroxy-tetradeca-1,3,5,7-tetraenyl)-oxiranyl]-butyric acid ethyl ester 
• 94235-42-4 4-[(2S,3S)-3-((1E,3E,5Z,7E)-(R)-9-Hydroxy-tetradeca-1,3,5,7-tetraenyl)-oxiranyl]-butyric acid 
• 94235-41-3 4-[(2R,3R)-3-((1E,3E,5E,7E)-(S)-9-Hydroxy-tetradeca-1,3,5,7-tetraenyl)-oxiranyl]-butyric acid ethyl ester 
• 201672-53-9 [(S)-((E)-1-But-1-en-3-ynyl)-hexyloxy]-tert-butyl-dimethyl-silane 
• 193410-68-3 (S)-3(E)-decen-1-yn-5-ol 
• 102354-82-5 methyl 4-(5-formyl-2,2-dimethyl-1,3-dioxolan-4-yl)butanoate 
• 76745-15-8 4-((4S,5R)-5-Hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-yl)-butyric acid methyl ester 
• 78606-80-1 5(S), 6(R), 7-trihydroxyheptanoic acid methyl ester 
• 97643-35-1 lipoxin A methyl ester 
• 94235-50-4 (7E,9E,11Z,13E)-(5S,6R,15S)-15-Hydroperoxy-5,6-dihydroxy-icosa-7,9,11,13-tetraenoic acid 
• 94235-42-4 epi-lipoxin A₄ 
• 94235-57-1 (5S,6R,15S)-(7E,9E,11Z,13E)-5,6-O-carbonyl lipoxin A₄ ethyl ester 
• 506-32-1 all cis 5,8,11,14-eicosatetraenoic acid 
• 94235-45-7 Benzoic acid (2E,4E,6Z,9Z)-(R)-1-((S)-4-ethoxycarbonyl-1-hydroxy-butyl)-pentadeca-2,4,6,9-tetraenyl ester 

Downstream Products

• 97643-35-1 lipoxin A methyl ester 

Relevant academic research and scientific papers

5 S,15 S-Dihydroperoxyeicosatetraenoic Acid (5,15-diHpETE) as a Lipoxin Intermediate: Reactivity and Kinetics with Human Leukocyte 5-Lipoxygenase, Platelet 12-Lipoxygenase, and Reticulocyte 15-Lipoxygenase-1

The reaction of 5S,15S-dihydroperoxyeicosatetraenoic acid (5,15-diHpETE) with human 5-lipoxygenase (LOX), human platelet 12-LOX, and human reticulocyte 15-LOX-1 was investigated to determine the reactivity and relative rates of producing lipoxins (LXs). 5-LOX does not react with 5,15-diHpETE, although it can produce LXA4 when 15-HpETE is the substrate. In contrast, both 12-LOX and 15-LOX-1 react with 5,15-diHpETE, forming specifically LXB4. For 12-LOX and 5,15-diHpETE, the kinetic parameters are kcat = 0.17 s-1 and kcat/KM = 0.011 μM-1 s-1 [106- and 1600-fold lower than those for 12-LOX oxygenation of arachidonic acid (AA), respectively]. On the other hand, for 15-LOX-1 the equivalent parameters are kcat = 4.6 s-1 and kcat/KM = 0.21 μM-1 s-1 (3-fold higher and similar to those for 12-HpETE formation by 15-LOX-1 from AA, respectively). This contrasts with the complete lack of reaction of 15-LOX-2 with 5,15-diHpETE [Green, A. R., et al. (2016) Biochemistry 55, 2832-2840]. Our data indicate that 12-LOX is markedly inferior to 15-LOX-1 in catalyzing the production of LXB4 from 5,15-diHpETE. Platelet aggregation was inhibited by the addition of 5,15-diHpETE, with an IC50 of 1.3 μM; however, LXB4 did not significantly inhibit collagen-mediated platelet activation up to 10 μM. In summary, LXB4 is the primary product of 12-LOX and 15-LOX-1 catalysis, if 5,15-diHpETE is the substrate, with 15-LOX-1 being 20-fold more efficient than 12-LOX. LXA4 is the primary product with 5-LOX but only if 15-HpETE is the substrate. Approximately equal proportions of LXA4 and LXB4 are produced by 12-LOX but only if LTA4 is the substrate, as described previously [Sheppard, K. A., et al. (1992) Biochim. Biophys. Acta 1133, 223-234].

COMPOSITIONS AND METHODS RELATING TO SALTS OF SPECIALIZED PRO-RESOLVING MEDIATORS OF INFLAMMATION

The present invention relates to compounds of Formulas I-IV, which are salts of special lipid mediators of inflammation, compositions containing same, and methods of using same in the treatment of various diseases and disorders characterized by chronic or excessive inflammation, or both.

Stereoselective total synthesis of 5(S), 6(R), 15(S)-trihydroxy-7(E), 9(E), 11(Z), 13(E)-eicosatetraenoic acid (Lipoxin A)

A stereoselective synthesis of the title compound from D-xylose using zinc mediated deoxygenation of 4-hydroxy-2-butenoic acid moiety and base induced double elimination of 4,5-epoxy allyl chloride as key steps is described.

SYNTHESIS OF 5S-HYDROXY-14,15 LTA4 A BIOGENIC PRECURSOR TO THE LIPOXINS

A synthesis of 5S-hydroxy-14,15-LTA4 10 an intermediate in the biosynthesis of the lipoxins is described.

Enantiospecific and Stereospecific Synthesis of Lipoxin A. Stereochemical Assignment of the Natural Lipoxin A and Its Possible Biosynthesis

Both chemical and enzymatic steps were employed to convert leukotriene A4 and its unnatural epoxide isomers into four diastereomeric 5(S),6(S),15(S)-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acids, possible structures for lipoxin A.These compounds were correlated with trihydroxy tetraene eicosatetraenoic acids derived from tetraene epoxide 3, and the relative stereochemistries of the 5 and 6 positions were assigned.These assignments were confirmed by total synthesis of two diastereomers of lipoxin A.One of these isomers, 5(S),6(S),15(S)-trihydroxy-7-9,13-trans-11-cis-eicosatetraenoic acid (1b), corresponded to lipoxin A derived from natural sources.The structure and possible biosyntheses of lipoxin A are proposed.

SYNTHESIS OF LIPOXINS: TOTAL SYNTHESIS OF CONJUGATED TRIHYDROXY EICOSATETRAENOIC ACIDS

The first synthesis of a conjugated trihydroxy eicosatetraenoic acid, a possible structure for Lipoxin A is described.A biomimetic approach was utilized.