TOTAL SYNTHESIS AND BIOLOGICAL SIGNIFICANCE OF PROSTAGLANDIN D2 AND E2 METABOLITES

Abstract

I. Prostaglandin E2 (PGE2) is a cyclic, oxygenated metabolite of arachidonic acid that has been shown to play a role in the pathophysiology of many diseases including arthritis, cardiovascular disease, breast cancer, colorectal cancer, and head and neck cancer. The primary urinary metabolite of PGE2 is PGE-M and has been used as a biomarker to study PGE2 metabolism of the aforementioned diseases. Recently, it has come to our attention that tetranor PGE1 is another metabolite of PGE2 and can also potentially be used as a biomarker for colon cancer. Unlike PGE-M, tetranor PGE1 is not commercially available and thus there was a need for a direct synthesis. This work summarizes the total synthesis of tetranor PGE1.

II. Prostaglandin D2 (PGD2) levels affect smooth muscle contraction, sleep, platelet aggregation, anaphylaxis and many diseases, such as mastocytosis. Interestingly, PGD2 has three major metabolites: PGD-M, tetranor PGDM, and 15-deoxy 12, 14 – PGJ2. While their respective routes of metabolism are understood, their function in different disease states remains unknown. Though there has been one successful synthesis of PGD-M, there is a need for a more direct and economic route to continue studies on PGD2 metabolism. This work summarizes the total synthesis of PGD-M.