Water Soluble Prostagandin E1 Prodrugs
This project was given for the purpose of synthesizing crystalline, stable, water-soluble esters which will be tested for the treatment of ductus arteriosus. This project was to synthesize a new class of prodrug consisting of crystalline C1-esters of prostaglandin E1 (PGE1) to provide water soluble derivatives with improved solid state stability of prostaglandin E1. PGE1 is a crystalline solid (m.p. 115-117’) which is stable at room temperature for short periods but, upon continued storage at room temperature, liquefaction and degradation occur with the loss of biological activity. PGE1 contains a five membered ring with one of the hydroxyls in B-position to the keto group which explains the lability to acid or base. Treatment of PGE1 with weak bases or weak acids rapidly destroys the biological activity with the formation of the d, B-unsaturated ketone, PGA1 (absorb at 217 mu) that then rearranges to the doubly conjugated ketone, PGB1 (absorb at 278 mu). This degradation can be eliminated by continuing solid state stability and this solid state stability can be attained with high melting.