The resolution of racemic hydroperoxides: a chromatography-based separation of perketals derived from arachidonic, linoleic, and oleic acid hydroperoxides.
The resolution of racemic hydroperoxides: a chromatography-based separation of perketals derived from arachidonic, linoleic, and oleic acid hydroperoxides.
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外消旋氢过氧化物的拆分：基于色谱法分离源自花生四烯酸、亚油酸和油酸氢过氧化物的过缩酮。
DOI：
10.1021/tx00015a008
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发表时间：
1990
影响因子：
4.1
通讯作者：
Morelli,J
中科院分区：
文献类型：
--
作者：
Porter,NA;Dussault,P;Breyer,RA;Kaplan,J;Morelli,J
尽管光学纯的不饱和氢过氧化物在生物学、化学和医学上具有重要意义，但目前还没有合成这些不稳定化合物的一般方法。我们开发了一种手性乙烯醚，它与外消旋氢过氧化物反应，产率高，生成非对映体的过酮。这些perketals可以通过液相色谱分离并去除手性基团，以提供高度富集的过氧化氢对映体（> 99%对映体过量）。我们手上最成功的手性试剂是来自írans-2-phenylcyclohexanol的2-丙烯醚。使用该乙烯醚，氢过氧化物很容易生成过酮，对正相和反相色谱都很稳定，并且氢过氧化物在温和酸条件下不外消旋，收率高。一些手性氢过氧化物已被此方法分解：-苯乙基氢过氧化物，2-辛烷基氢过氧化物，以及一些由油酸、亚油酸和花生四烯酸衍生的氢过氧化物。脂肪酸氢过氧化物是由脂氧合酶催化的多不饱和脂肪酸转化而形成的(1)。这些氢过氧化物在形成各种具有重要生物学意义的化合物中起着重要的中间产物作用。例如，脂肪酸氢过氧化物是白三烯(2)和脂毒素(3)的前体，最近在亚麻、玉米和珊瑚中报道了一种新的生物化学途径，涉及脂肪酸氢过氧化物转化为过氧化氢烯(4)。在脂氧合酶反应中产生一个新的立体中心，从天然来源分离的脂肪酸氢过氧化物如果通过酶的方式形成，本质上是一个对映体（1,5）。例如，当大豆脂氧合酶作用于亚油酸时，形成13 (S)-过氧化氢，而当花生四烯酸是底物时，该酶产生15 (S)-过氧化氢，15 (5)-HPETE, 1。另一方面，珊瑚中的脂氧合酶将花生烯酸转化为8 （/?）-HPETE(4)。脂肪酸底物的非酶外氧化也产生脂肪酸氢过氧化物(5)，并且在该过程中形成外消旋混合物(6)。
In spite of the importance of optically pure unsaturated hydroperoxides in biology, chemistry, and medicine, no general methodfor synthesizing these labile compounds has been reported. We have developed a chiral vinyl ether that reacts with racemic hydroperoxides to give diastereomeric perketals in high yield. These perketals can be separated by liquid chromatography and thechiral group removed to provide highly enriched hydroperoxide enantiomers (> 99% enantiomeric excess). The chiral reagent that has been most successful in our hands is the 2-propenyl ether derived from írans-2-phenylcyclohexanol. By use of this vinyl ether, perketals are readily formed from hydroperoxides, they are stable to normal-and reverse-phase chro-matography, and the hydroperoxide is regenerated from the perketal without racemization in high yield with mild acid. Several chiral hydroperoxides have been resolved by this procedure:-phenethyl hydroperoxide, 2-octyl hydroperoxide, and a number of hydroperoxides derived from oleic, linoleic, and arachidonic acids.Fatty acid hydroperoxides are formed by a lipoxygenase enzyme catalyzed conversion of polyunsaturated fatty acids (1). These hydroperoxides serve as important interme-diates in the formation of diverse compounds of biological importance. For example, fatty acid hydroperoxides are precursors to the leukotrienes (2) and the lipoxins (3), and recently a new biochemical pathway involving the con-version of fatty acid hydroperoxides to aliene oxides has been reported in flax, corn, and coral (4). A new stereocenter is generated in the lipoxygenase reaction, and fatty acid hydroperoxides isolated from natural sources are essentially one enantiomer if formed enzymatically (1, 5). For example, the 13 (S)-hydroperoxide is formed when soybean lipoxygenase acts on linoleic acid, while this enzyme gives the 15 (S)-hydroperoxide, 15 (5)-HPETE, 1 when arachidonic acid is the substrate. On the other hand, lipoxygenase enzyme in coral converts ara-chidonic acid into 8 (/?)-HPETE (4). Nonenzymatic aut-oxidation of fatty acid substrates also gives fatty acid hydroperoxides (5), and racemic mixtures are formed in this process (6).