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).