TOTAL SYNTHESIS OF ISO[4]-LEVUGLANDIN E-2

Iso[4]-levuglandin E-2 (iso[4]-LGE(2), tyl-6-formyl-9-hydroxy-7(E),11( Z)-heptadecadienoic acid) is a structural isomer of levuglandin E-2 yl -9-formyl-12-hydroxy-5(Z),10(E)-heptadecadienoic acid) that we postula te to be generated during autoxidation of arachidonic acid or arachido nate esters. To facilitate detection and identification of iso[4]-LGE( 2) in biological samples, a succinct total synthesis was developed tha t depends on conjugate addition of a higher order vinyl cyanocuprate t o a gamma-alkoxy enone to provide a key carbon-carbon bond-forming ste p. Bismethoxime pentafluorobenzyl ester trimethylsilyl ether derivativ es of LGE(2) and iso[4]-LGE(2) were prepared and shown to be suitable for mass spectral identification of these highly oxidized lipids.