Development of Methods for Synthesis of Stereo-Selective Lipid Peroxides

亚麻酸经自氧化得到9-和13-过氧氢衍生物。含3个以上双键的脂肪酸自氧化副产物为环状过氧化物。但在该体系中加入供氢体，增加了氢过氧化物生成的选择性。由亚麻酸形成四种不同的氢过氧化物，由花生四烯酸形成六种氢过氧化物。用高效液相色谱法对上述氢过氧化物进行了分离纯化。磷脂、甘油三酯和胆固醇酯的自氧化也产生它们的氢过氧化物，但它们的异构体不易分离。在人血浆中检测到约3 nM的胆固醇酯氢过氧化物。根据化合物的保留时间，确定它们是胆固醇亚油酸酯和胆固醇花生四烯酸酯的氢过氧化物。建立了以单丹酰尸胺为荧光衍生试剂的皮摩尔级脂肪酸氧化产物的检测方法。1%法可用于生物样品中脂质过氧化物的定量和定性分析，对了解脂质过氧化物是否通过非酶途径形成具有重要意义。在这个项目中开发的方法将有助于回答这个问题。

The Autoxidation of linolenic acid gave its 9- and 13-hydroperoxy derivatives. The autoxidation of fatty acids which have more than 3 double bonds gave cyclic peroxides as a by-product. But the addition of hydrogen donor in this system increased the selectivity for the formation of hydroperoxides. Four different hydroperoxides were formed from linolenic acid and six hydroperoxides from arachidonic acid. These hydroperoxides mentioned above were separated and purified by High Performance Liquid Chromatography. The autoxidation of phospholipids, triglycerides, and cholesteryl esters also gave their hydroperoxides, but the separation of their isomers were not easy.About 3 nM of cholesteryl ester hydroperoidde was detected in human blood plasma. According to the retention times of the compounds, they were ascribed to be hydroperoxides of cholesteryl linolate and cholesteryl arachidonate. On the other hand, phospholipid hydroperoidde was not detected.A methods for the detection of picomole level of fatty acid oxidation products was developed using monodansyl cadaverin as a fluorescent derivatizing reagent 1% method will be useful for the quantitation and qualification of lipid peroxides derived from biological samples.It is very important know whether lipid peroxides are formed by non-enzymatic pathway or not. The methods developed in this project will be useful to answer this question.