Preparative Singlet Oxygenation of Linoleate Provides Doubly Allylic Dihydroperoxides: Putative Intermediates in the Generation of Biologically Active Aldehydes in Vivo

Department of Chemistry, Case Western Reserve University, Cleveland, Ohio, United States
The Journal of Organic Chemistry (Impact Factor: 4.72). 08/2006; 71(15):5607-15. DOI: 10.1021/jo0605795
Source: PubMed


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 as key intermediates in the free radical-promoted oxidative fragmentation of linoleate that generates aldehydes, such as the cytotoxic gamma-hydroxyalkenal 4-hydroxy-2-nonenal (HNE), in vivo. We now report an efficient preparation of regioisomerically pure 9,12- and 10,13-diHPODE, devised to enable studies of their fragmentation reactions. Free radical-induced oxygenation of linoleate initially generates conjugated monohydroperoxy octadecadienoates (HPODEs) that are then converted into diHPODEs. In contrast, we found that singlet oxygenation of conjugated HPODEs does not produce diHPODEs. Unconjugated HPODEs are unique products of singlet oxygenation of linoleate that are coproduced with conjugated HPODEs. Preparative separation of the mixture of regioisomeric mono and diHPODEs generated by singlet 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 accomplished under 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. Each of these was subsequently converted into a different, regioisomerically pure, diHPODE through further singlet oxygenation.

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Available from: Wujuan Zhang, Aug 19, 2015
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    • "However, Pryor et al. [36] have proposed a mechanism by which hydroperoxides of a diene system (e.g., linoleic acid) may produce such bicyclic endoperoxides. Zhang et al. [37] reported the production of doubly allylic dihydroperoxide from linoleic acid using singlet oxygen. This suggests that LOP may contain γ-ketoaldehydes with reactivity and behavior similar to those of isoLG's. "
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