The first total synthesis of the highly unstable biological mediator 1
2-ketoeicosatetraenoic acid (12-KETE) 3 and its 8,9-trans-isomer 20 is
presented. The strategy focuses on the stable precursor dithiane 13 a
nd its conversion to 9 and 20. Biochemical experiments show that the t
wo isomers are not interconverted in vivo, raising the possibility tha
t the trans-isomer 20 may be formed by a primary biochemical mechanism
.