A new approach to the synthesis of polyunsaturated deuterated isoprostanes: Total synthesis of d4-5-epi-8,12-iso-iPF3α-VI and d4-8,12-iso-iPF3α-VI

The total and stereospecific synthesis of d4-5-epi-8,12-iso-iPF3α-VI 55 and d4-8,12-iso-iPF3α-VI 64, EPA-derived all-syn-isoprostanes (iPs), has been accomplished. Because of issues related to volatility and yield with some of the primary deuterated synthons an improved synthesis is presented. These two deuterated analogs were used to discover and quantify the presence of the corresponding endogenous isoprostanes in human urine. These assays may serve as a valuable index of oxidative stress in population with omega-3 fatty acid enriched diets containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and may also be useful as an index of the severity of inflammatory diseases such as atherosclerosis and Alzheimer’s disease.

d4-5-epi-8,12-iso-iPF3α-VI 55 and d4-8,12-iso-iPF3α-VI 64 were synthesized using a new strategy to prepare the volatile D4 synthons. 55 and 64 were subsequently used to quantify iPs in urine.Figure optionsDownload as PowerPoint slide