12-Oxo-LTB4, a key pivotal intermediate in LTB4 metabolism

Article abstract of DOI:10.1021/jo00111a044

The first total synthesis of the very unstable and elusive biochemical intermediate 5(S)-hydroxy-12-oxo-6(Z),8(E),10(E),14(Z)-eicosatetraenoic acid (12-oxo-LTB₄) (2) has been accomplished. Incubation of the synthetic 12-oxo-LTB₄ (2) with human keratinocytes produced 5(S),12-dihydroxy-6-glutathionyl-7(E),9(E),14(Z)-eicosatrienoic acid (c-LTB₃) and 5(S),12-dihydroxy-6-cysteinylglycyl-7(E),9(E),14(Z)-eicosatrienoic acid (d-LTB₃), two new intriguing mediators which have been identified recently during the incubations of LTB₄ with keratinocytes. We have also confirmed the identity of 12-oxo-LTB₄ prepared from porcine leukocytes by comparison with the synthetic material and identified the formation in these incubates of the 6-trans-isomer of 12-oxo-LTB₄.