Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization.

Abstract

Prostaglandin D₂ (PGD₂) is a key pathophysiological mediator in many human diseases and biological pathways. Tricyclic prostaglandin D₂ metabolite methyl ester (tricyclic-PGDM methyl ester), the major urinary metabolite of PGD₂, can be used as a clinical indicator for PGD₂ overproduction. However, the limited amount of tricyclic-PGDM methyl ester available has prevented its practical use, and synthesis methods for tricyclic-PGDM methyl ester are required. Based on the utilization of oxidative radical cyclization for the stereoselective construction of the cyclopentanol subunit with three consecutive stereocenters, we describe an asymmetric total synthesis of tricyclic-PGDM methyl ester in 9 steps and 8% overall yield.