Preparative singlet oxygenation of linoleate provides doubly allylic dihydroperoxides: putative intermediates in the generation of biologically active aldehydes in vivo.
Preparative singlet oxygenation of linoleate provides doubly allylic dihydroperoxides: putative intermediates in the generation of biologically active aldehydes in vivo.
复制标题
亚油酸酯的制备型单线态氧化提供双烯丙基二氢过氧化物：体内产生生物活性醛的推定中间体。
DOI：
10.1021/jo0605795
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Salomon,RobertG
中科院分区：
文献类型：
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作者：
Zhang,Wujuan;Sun,Mingjiang;Salomon,RobertG
光诱导氧合在视网膜中产生具有生物活性的氧化截短的脂质。此前，双烯丙基二氢过氧化物，9,12-二氢过氧十八-10,13-二烯酸（9,12-diHPODE）和10,13-二氢过氧十八-8,11-二烯酸（10,13-二HPODE）被认为是自由基促进的亚油酸酯氧化裂解中的关键中间体。醛类，例如体内具有细胞毒性的 γ-羟基烯醛 4-羟基-2-壬烯醛 (HNE)。我们现在报道了一种区域异构纯 9,12- 和 10,13-diHPODE 的有效制备方法，旨在研究其断裂反应。自由基诱导的亚油酸酯氧化最初生成共轭单氢过氧化十八碳二烯酸酯 (HPODE)，然后转化为二HPODE。相反，我们发现共轭 HPODE 的单线态氧化不会产生二HPODE。非共轭 HPODE 是亚油酸酯单线态氧化的独特产物，与共轭 HPODE 联产。亚油酸单线态氧化产生的区域异构单和二HPODE 混合物的制备分离是不切实际的。然而，一个简单的策略就解决了这个问题。因此，通过与N-苯基三唑啉二酮反应，可以在温和条件下将不需要的共轭HPODE选择性转化为Diels-Alder加合物。这些加合物很容易被去除，然后可以很容易地以区域异构纯的形式分离出剩余的两个未缀合的 HPODE。这些物质随后通过进一步的单线态氧化转化为不同的、区域异构纯的二HPODE。
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 γ-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 withN-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.