Transformation of Prostaglandin D2 to 11-Dehydro Thromboxane B2 by Baeyer-Villiger Oxidation.

Abstract

Prostaglandin D2 is one of five chief prostanoids formed in the cyclooxygenase pathway of arachidonic acid oxidation. Except for a single oxygen atom, PGD2 is structurally identical to 11-dehydro thromboxane B2 (11d-TxB2 ), a urinary metabolite of the pro-aggregatory platelet activator, thromboxane A2 . The close structural relationship suggested that one might be transformed to the other. Accordingly, we tested whether the cyclopentanone of PGD2 can be expanded to the δ-lactone of 11d-TxB2 in a Baeyer-Villiger oxidation. Oxidation of PGD2 with two standard oxidants showed that 11d-TxB2 was formed only with H2 O2 but not with peracetic acid. Byproducts of the H2 O2 -mediated oxidation were hydroperoxide derivatives and isomers of PGD2 . Chemical oxidation of PGD2 to 11d-TxB2 may be a model for an equivalent enzymatic transformation, suggesting a possible link in the metabolism of PGD2 and thromboxane A2 .