Diels-Alder approach to isoprostanes.: Total synthesis of iPF2α-V

Isoprostanes (iPs) are a group of natural products formed in vivo by a free-radical oxygenation of arachidonic acid. They are isomeric with prostaglandins; whereas enzymatically produced prostaglandins, such as PGF(2 alpha) have the two side chains in the trans stereochemistry, the side chains of the isoprostanes are mostly in the cis configuration. A novel synthesis of iPs is described and illustrated with the synthesis of iPF(2 alpha)-V, 8. The synthetic material allowed us to identify this iP in human urine. Because of this cis relationship between the two side chains in the structures of iPs, we selected a synthetic design based on the Diels-Alder rection which will guarantee that the two side chains, which will be derived from the diene part, will be cis to each other. By substituting the OH of the hydroxycyclopentenone 14 with a bulky TBDPS group, we controlled the face selectivity of the approaching diene 17a from the less hindered top face of the five-membered ring. We would obtain eventually the two OH groups of the isoprostanes cr to the plane of the ring and the two isoprostane side chains cis to each other and anti to the OH groups.