6(S)-Lipoxin A4

The lipoxins are trihydroxy fatty acids containing a 7,9,11,13-conjugated tetraene. Lipoxin A4 (LXA4) was first described as a metabolite of 15-HpETE and/or 15-HETE when added in vitro to isolated human leukocytes. The material obtained in this manner consists of at least four distinct isomers: 5(S), 6(S); 5(S), 6(R); and the 11-trans and 11-cis isomers of each of these. 6(S)-LXA4 is one of the original four metabolites first identified by Serhan, Nicolaou, and Samuelsson. It was considered to be an artifact by these authors because it lacked the potency of the 5(S),6(R) isomer with respect to contraction of isolated guinea pig lung parenchymal strips. It has not been possible to isolate “natural” LXA4 from humans or other mammals in amounts sufficient for determination of absolute stereochemistry. Most authors refer to LXA4 as the 5(S),6(R), 11-cis isomer, but it is not clear that biological systems are aware of or agree with these conventions. Historically, conjugated tetraenes flanked by hydroxyl groups of mixed stereochemistry have been marketed as 'Lipoxin A4' by some biomolecular supply companies. The availability of single pure LXA4 enantiomers should help to reduce the confusion this has caused.