CHEMICAL SYNTHESIS AND ACTIONS OF 11,12-THIIRANO-HEPOXILIN A(3)

A novel analog of hepoxilin A(3) has been chemically synthesized in wh ich the 11,12-epoxide group has been altered to a thiirano group. This has been accomplished through allylic rearrangement of unnatural (11R ,12R)-hepoxilin B-3 under Mitsunobu conditions, first into unnatural ( 11R,12R)-hepoxilin A(3), followed by conversion of this compound with inversion of the epoxide centers into the thiirano-hepoxilin A(3) havi ng the natural 11S,12S configuration. We also report herein evidence s howing that thiirano-hepoxilin A(3) raises intracellular calcium conce ntrations in intact human neutrophils.