Adiyaman M, Lawson J A, Khanapure S P, FitzGerald G A, Rokach J
Department of Chemistry, Florida Institute of Technology, Melbourne, Florida, 32901-6975, USA.
Anal Biochem. 1998 Aug 15;262(1):45-56. doi: 10.1006/abio.1998.2767.
Isoprostanes are a new class of natural products formed in humans as a result of free-radical-catalyzed lipid peroxidation of polyunsaturated fatty acids. These endogenous compounds are isomeric with biologically active prostaglandins and have great promise as markers of oxidant stress in vivo. iPF2alpha-III (previously 8-iso-PGF2alpha), an isoprostane from Class III (previously known as Class IV), has been used as an index of free-radical-induced oxidative stress. This isoprostane is also produced by the cyclooxygenase enzymes COX1 and COX2. We are proposing a new reliable index of oxidative stress based on iPF2alpha-VI (previously IPF2alpha-I), a new Class VI isoprostane we recently discovered. The advantages of iPF2alpha-VI are that it is several fold more abundant in urine than iPF2alpha-III, hence allowing more accurate determinations. Equally, the proximity of the C-5 OH function to the carboxylic acid allows the formation of the lactone 35 which is easier to purify from other iPs which cannot form such lactones. We have performed the first total synthesis of d4-iPF2alpha-VI by using two synthons, (3,3,4,4-d4)-hexylphosphonium bromide 23 prepared from 5-hexynol and syn-anti-syn lactone 25 synthesized from d-glucose. We have developed two variants of a sensitive GC/MS assay using the synthetic d4-iPF2alpha-VI as an internal standard to determine the levels of endogenous iPF2alpha-VI in biological fluids. Quantification of iPF2alpha-VI formed in vivo may be a more reliable index to assess oxidant stress in humans.
异前列腺素是一类新的天然产物，在人体内由多不饱和脂肪酸的自由基催化脂质过氧化反应形成。这些内源性化合物与具有生物活性的前列腺素同分异构，有望成为体内氧化应激的标志物。iPF2α-III（以前称为8-异-PGF2α），一种来自III类（以前称为IV类）的异前列腺素，已被用作自由基诱导氧化应激的指标。这种异前列腺素也由环氧化酶COX1和COX2产生。我们基于iPF2α-VI（以前称为IPF2α-I）提出了一种新的可靠的氧化应激指标，iPF2α-VI是我们最近发现的一种新的VI类异前列腺素。iPF2α-VI的优点是它在尿液中的含量比iPF2α-III高几倍，因此可以进行更准确的测定。同样，C-5羟基与羧酸的接近使得内酯35得以形成，这比从其他不能形成此类内酯的异前列腺素中更容易纯化。我们通过使用两种合成子进行了d4-iPF2α-VI的首次全合成，由5-己炔醇制备的(3,3,4,4-d4)-己基溴化鏻23和由d-葡萄糖合成的顺-反-顺内酯25。我们开发了两种灵敏的GC/MS分析方法变体，使用合成的d4-iPF2α-VI作为内标来测定生物流体中内源性iPF2α-VI的水平。体内形成的iPF2α-VI的定量可能是评估人类氧化应激更可靠的指标。
