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The pure reticulocyte lipoxygenase converts 1 5LS-hydroxy-5,8,1 1,13(2,Z,Z,E)-icosatetraenoic acid (1 5~~-HETE) methyl ester to a complex mixture of products containing 5~, , 1 4~~, 1 5~~-trihydro(pero)xy-6E,8Z,lOE,12E-icosatetraenoate methyl ester (lipoxin B methyl ester), 5~, , l SL,-D~H(P)ETE methyl ester and four 8 , 1 5~~-DiH(P)ETE methyl ester isomers [DiH(P)ETE = dihydro(pero)xy-icosatetraenoic acid].After a short incubation period (15 min) 5os,15~,-DiH(P)ETE methyl ester was found to be the main product, whereas after a 3-h incubation lipoxin B methyl ester was the predominant product. The reaction shows a remarkable stereoselectivity since only small amounts of other trihydroxy tetraenes are formed. Anaerobiosis, heat inactivation of the enzyme, or incubation in the presence of lipoxygenase inhibitors (icosatetraynoic acid, nordihydroguaiaretic acid) completely abolished the reaction. The complete steric structure of the major tetraene product (lipoxin B methyl ester) was established by ultraviolet spectroscopy, HPLC on four different types of columns, gas chromatography/mass spectrometry, gas/liquid chromatography of the ozonolysis fragments of the menthoxycarbonyl derivatives, and by 400-MHz 'H-NMR.Atmospheric oxygen was incorporated at carbon-5 and carbon-14 into the major product. 5~~, 1 5~~-DiH(P)ETE methyl ester was shown to be an intermediate in the synthesis. Lipoxin B was also formed during the oxygenation of arachidonic acid, 1 SL,-HETE and 5~~, l SL,-D~HETE. The results presented here indicate that lipoxin B can be formed by pure lipoxygenases via a sequential oxygenation of arachidonic acid or its hydro(pero)xy derivatives.

The total syntheses of 12-HETE (1) in racemic form and of both enantiomers in optically pure form are reported. The synthesis of a metabolite of 12(S)-HETE, 12,20-diHETE (2), in optically pure form is also reported.As part of an ongoing research project into the lipoxygenase-derived metabolites of arachidonic acid, we became interested in 12-hydroxyeicosatetraenoic acid (12-HETE, 1). This natural product is generated from co2h ho,"12-HETE 2: R = CH2OH 12,20-diHETE arachidonic acid by a 12-lipoxygenase enzyme, which is found in platelets1 and skin, keratinocytes.2 The 12-HETE is of particular interest since it has been detected in high concentrations in psoriatic lesions3 and has been shown to possess both chemotactic and chemokinetic properties. The 12(S)-HETE is also the major lipoxygenase-derived arachidonic acid metabolite produced by the platelet and has been postulated as a mediator of the circulatory sys-

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