| Abstract
| - Photoinduced oxygenation generates biologically active, oxidatively truncated lipids in the retina.Previously, doubly allylic dihydroperoxides, 9,12-dihydroperoxyoctadeca-10,13-dienoic acid (9,12-diHPODE) and 10,13-dihydroperoxyoctadeca-8,11-dienoic acid (10,13-diHPODE), were postulated askey intermediates in the free radical-promoted oxidative fragmentation of linoleate that generates aldehydes,such as the cytotoxic γ-hydroxyalkenal 4-hydroxy-2-nonenal (HNE), in vivo. We now report an efficientpreparation of regioisomerically pure 9,12- and 10,13-diHPODE, devised to enable studies of theirfragmentation reactions. Free radical-induced oxygenation of linoleate initially generates conjugatedmonohydroperoxy octadecadienoates (HPODEs) that are then converted into diHPODEs. In contrast, wefound that singlet oxygenation of conjugated HPODEs does not produce diHPODEs. UnconjugatedHPODEs are unique products of singlet oxygenation of linoleate that are coproduced with conjugatedHPODEs. Preparative separation of the mixture of regioisomeric mono and diHPODEs generated bysinglet oxygenation of linloeate is impractical. However, a simple tactic circumvented the problem. Thus,selective conversion of the undesired conjugated HPODEs into Diels−Alder adducts could be accomplishedunder mild conditions by reaction with N-phenyltriazolinedione. These adducts were readily removed,and the two remaining unconjugated HPODEs could then be easily isolated regioisomerically pure. Eachof these was subsequently converted into a different, regioisomerically pure, diHPODE through furthersinglet oxygenation.
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