DEVELOPMENT OF THE CARBOCYCLIC NUCLEOSIDE MDL 201449A - A TUMOR-NECROSIS-FACTOR-ALPHA INHIBITOR

An efficient synthesis of )-(-)-4-tert-butyldimethylsilyloxy-2-cyclope ntenyl acetate and )-(-)-4-tert-butyldimethylsilyloxy-2-cyclopentenol is described utilizing a furfuryl alcohol rearrangement, followed by a lithium aluminum hydride reduction with high facial selectivity and a n efficient enzymatic resolution with pancreatin. Both of these interm ediates were successfully utilized in the preparation of the carbocycl ic nucleoside N-[(1'R,3'R)-trans-3'-hydroxycyclopentanyl]adenine hydro chloride, an agent which inhibits the formation of tumor necrosis fact or-alpha.