Isoprostanes, biomarkers of lipid peroxidation in humans. Part 1. Nomenclature and synthesis

The synthesis of prostaglandins has been a subject of chemical attractiveness for the last 40 years with the successful strategy developed by Corey et al. via a formyl-lactone in the trans-PG series, derived from the action of cyclooxygenases (COXs). The non-enzymatic metabolic scheme of arachidonic acid, as a free radical catalyzed mechanism, has introduced new data concerning the reactivity of the arachidonyl radical in the absence of COXs and also a growing interest in the total synthesis of isoprostanes and analogues. The potent biological activity of these compounds has been attracting intense research interest since they were detected in humans as well as animal models in the early 1990s. The measurement of these isoprostanes has been regarded as one of the most useful non-invasive biomarkers for oxidative stress status. Two mechanisms for their biosynthesis have been proposed. In the first mechanism, a peroxyl radical undergoes successive 5-exo cyclizations analogous to the enzymatic mechanism proposed for prostaglandin biosynthesis. The second mechanism starts with a 4-exo cyclization of a peroxyl radical leading to an intermediate dioxetane. During the last two decades, several approaches towards the synthesis of isoprostanes and analogues have been reported in the literature by several groups of chemists. Finally, to date, two nomenclatures have been proposed by Taber et al. and Rokach et al., but only Taber's nomenclature have been approved by IUPAC. (c) 2004 Elsevier SAS. Tons droits reserves.