Synthesis of the F11334ʹs from o-prenylated phenols: μM inhibitors of neutral sphingomyelinase (N-SMase)

F11334A1, F11334A2, F11334A3, and their corresponding resorcinol analogs were synthesized along with F11334B1, and F11263. In the course of these synthetic studies, several conditions for manipulating (2,3-propanediol) and (2,3-epoxypropyl) o-substituted phenols were developed as well as a variety of conditions for cleavage of aryl O-t-butyl carbonates. From enzyme assays it appears that the hydroquinone nucleus is the essential structural necessary for N-SMase inhibition. Furthermore, it appears that this family of compounds is comprised of irreversible inhibitors.