Stereoselective Synthesis of MLN4924, an Inhibitor of NEDD8-Activating Enzyme

MLN4924 (1), which is in clinical trials as an anticancer agent, was stereoselectively synthesized from D-ribose via a route involving stereoselective reduction, regioselective cleavage of an isopropylidene moiety, and selective displacement of a cyclic sulfate moiety as key steps.