TOTAL SYNTHESIS OF A POTENT PROINFLAMMATORY 5-OXO-ETE AND ITS 6,7-DIHYDRO BIOTRANSFORMATION PRODUCT

The first total synthesis of a potent inflammatory mediator 5-oxo-6(E) ,8(Z), 11(Z),14(Z)-eicosatetraenoic acid (5-oxo-ETE) 2 and its biotran sformation product 6,7-dihydro-5-oxo-ETE 5 is reported. A convergent s ynthesis for the unstable title compounds is accomplished via two synt hons, dithiolane aldehyde 13 and bisdienyl phosphonium bromide 19. The synthetic 5-oxo-ETE 2 and its 8,9-trans isomer 3 were used to unequiv ocally confirm the structure of the biologically derived mediators. In addition, using synthetic 6,7-dihydro-5-oxo-ETE 5 we have been able t o identify in neutrophils the formation of 6,7-dihydro-5-oxo-ETE 5.