Synthetic Studies on Hemiketal E2 and 5-Hydroxy Prostaglandin E2 Novel Arachidonic Acid Metabolites

Abstract

The metabolites of arachidonic acid have long been studied for their intimate role in the human body inflammatory pathway. Inflammation is the body’s natural defense against foreign pathogens and maintains the body’s ability to regain homeostasis after injury. When acting properly the inflammatory pathway maintains normal bodily function. However, when improperly regulated inflammation can have severe deleterious effects resulting in a wide array of problems, such as tissue and cellular damage leading to disease such as cancer. The metabolites of arachidonic acid have been the subject of countless total syntheses, furthering both the fields of biology and chemical synthesis. The novel eicosanoids hemiketals E2 and D2, as well the 5-hydroxy prostaglandins E2 and D2, were discovered as the products of the crossover enzymatic pathway between 5-LOX and COX-2 at Vanderbilt by the Schneider group. It was originally believed that these two enzymatic pathways operated independently from one another, resulting in leukotrienes or prostaglandins, respectively. The hemiketals have been shown to stimulate angiogenesis of pulmonary endothelial cells, implying they may play a role in tissue repair, while the function of the 5-hydroxy prostaglandins remains unknown. However, they do not activate the same receptors as prostaglandin E2 and D2 implying a unique physiological function. The development of a concise and efficient synthesis towards hemiketal E2, the completion of 5 hydroxy PGE2 and the development of a concise synthesis towards 5 hydroxy PGD2 are discussed within.