First total synthesis of labeled EPA and DHA-derived A-type cyclopentenone isoprostanoids: [D sub(2)]-15-A sub(3t)-IsoP and [D sub(2)]-17-A sub(4t)-NeuroP

A-type cyclopentenone isoprostanoids are abundantly formed in vivo by radical peroxidation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are consumed daily for the prevention of cardiovascular and neurological pathologies. To facilitate in depth studies concerning the effects of these oxidized isoprostanoids on human health, labeled derivatives are necessary. In this paper, we have accomplished the first total synthesis of labeled A-type cyclopentenone isoprostanoids, namely 17,18-[D sub(2)]-15-A sub(3t)-IsoP and 19,20-[D sub(2)]-17-A sub(4t)-NeuroP. The two enantioselective routes are highly convergent, stemming from a common intermediate, readily available by a Julia-Kocienski reaction, and feature the semihydrogenation of an alkyne moiety for the installation of the labeled lower side chain.