Nakashima Fumie, Schneider Claus
Department of Pharmacology, Division of Clinical Pharmacology, and Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical School, Nashville, TN, 37232, USA.
Lipids. 2020 Jan;55(1):73-78. doi: 10.1002/lipd.12206. Epub 2019 Dec 12.
Prostaglandin D is one of five chief prostanoids formed in the cyclooxygenase pathway of arachidonic acid oxidation. Except for a single oxygen atom, PGD is structurally identical to 11-dehydro thromboxane B (11d-TxB ), a urinary metabolite of the pro-aggregatory platelet activator, thromboxane A . The close structural relationship suggested that one might be transformed to the other. Accordingly, we tested whether the cyclopentanone of PGD can be expanded to the δ-lactone of 11d-TxB in a Baeyer-Villiger oxidation. Oxidation of PGD with two standard oxidants showed that 11d-TxB was formed only with H O but not with peracetic acid. Byproducts of the H O -mediated oxidation were hydroperoxide derivatives and isomers of PGD . Chemical oxidation of PGD to 11d-TxB may be a model for an equivalent enzymatic transformation, suggesting a possible link in the metabolism of PGD and thromboxane A .
前列腺素D是花生四烯酸氧化环氧化酶途径中形成的五种主要前列腺素之一。除了一个氧原子外，PGD在结构上与11-脱氢血栓素B（11d-TxB）相同，11d-TxB是促聚集血小板激活剂血栓素A的尿液代谢产物。紧密的结构关系表明两者可能会相互转化。因此，我们测试了在拜耳-维利格氧化反应中，PGD的环戊酮是否可以扩展为11d-TxB的δ-内酯。用两种标准氧化剂氧化PGD表明，只有用过氧化氢氧化才会形成11d-TxB，而用过氧乙酸氧化则不会。过氧化氢介导的氧化反应的副产物是PGD的氢过氧化物衍生物和异构体。PGD化学氧化为11d-TxB可能是等效酶促转化的模型，这表明PGD和血栓素A的代谢可能存在联系。
