12-OXO-LTB(4), A KEY PIVOTAL INTERMEDIATE IN LTB(4) METABOLISM

The first total synthesis of the very unstable and elusive biochemical intermediate roxy-12-oxo-6(Z),8(E),10(E),14(Z)-eicosatetraenoic acid (12-oxo-LTB(4)) (2) has been accomplished. Incubation of the synthetic 12-oxo-LTB(4) (2) with human keratinocytes produced roxy-6-glutathion yl-7(E),9(E),14(Z)-eicosatrienoic acid (c-LTB(3)) and y-6-cysteinylgly cyl-7(E),9(E),14(Z)-eicosatrienoic acid (d-LTB(3)), two new intriguing mediators which have been identified recently during the incubations of LTB(4) with keratinocytes. We have also confirmed the identity of 1 2-oxo-LTB(4) prepared from porcine leukocytes by comparison with the s ynthetic material and identified the formation in these incubates of t he 6-trans-isomer of 12-oxo-LTB(4).