Synthesis and pharmacological evaluation of 5,6-exo-epoxy-7-oxabicyclo[2.2.1]heptane derivatives

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Abstract
[1.alpha., 2.beta.(5Z),3.beta.(1E,3S),4.alpha.,5.alpha.,6.alpha.]-7-[5,6-Epoxy-3-(3-cyclohexyl-3-hydroxy-3-methyl-1-propenyl)-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (31) and [1.alpha.,2.beta.(5Z), 3.beta.(1E,3S), 4.alpha.,5.alpha.,6.alpha.]-7-[5,6-epoxy-3-[3-hydroxy-5-(p-hydroxyphenyl)-1-pentenyl]-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid (37) were found to be selective TxA2 antagonists at the platelet and pulmonary thromboxane receptors. An efficient stereospecific synthesis of these compounds and a series of structural analogues is described. Compounds 31 and 37 both inhibited the bronchoconstriction induced by arachidonic acid in the anesthetized guinea pig.