Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106-7078, United States.
Bioorg Med Chem. 2011 Jan 1;19(1):580-7. doi: 10.1016/j.bmc.2010.10.058. Epub 2010 Oct 31.
The diverse biological activities of γ-hydroxyalkenal phospholipids and their involvement in disease are the subject of intense study. Phospholipid aldehydes, such as the 4-hydroxy-7-oxohept-5-enoic acid ester of 2-lyso-phosphatidylcholine (HOHA-PC), the 5-hydroxy-8-oxo-6-octenoic acid ester of 2-lyso-PC (HOOA-PC), and the 9-hydroxy-12-oxododec-10-enoic acid ester of 2-lyso-PC (HODA-PC), are generated by oxidative cleavage of polyunsaturated fatty acyl phospholipids. To facilitate investigations of their chemistry and biology, we now report efficient total synthesis of HOOA, HODA, and HOHA phospholipids. Because the target γ-hydroxyalkenals readily decompose through oxidation of the aldehyde group to a carboxylic acid or through cyclization to furans, these synthesis generate the sensitive functional array of the target phospholipids under mild conditions from acetal derivatives that are suitable for long-term storage.
γ-羟烯醛磷脂的多种生物活性及其在疾病中的作用是目前研究的热点。氧化断裂多不饱和脂肪酸磷脂可生成磷脂醛，如 2-溶血磷脂酰胆碱的 4-羟基-7-氧庚-5-烯酸酯（HOHA-PC）、2-溶血磷脂酰胆碱的 5-羟基-8-氧代-6-辛烯酸酯（HOOA-PC）和 2-溶血磷脂酰胆碱的 9-羟基-12-氧代-10-十二烯酸酯（HODA-PC）。为了便于研究其化学和生物学特性，我们现在报道了 HOOA、HODA 和 HOHA 磷脂的高效全合成方法。由于目标 γ-羟烯醛很容易通过醛基氧化为羧酸或通过环化生成呋喃而分解，因此这些合成方法从适合长期储存的缩醛衍生物中，在温和条件下生成了目标磷脂的敏感功能阵列。
