Concise stereocontrolled routes to fumagillol,fumagillin, and TNP-470

A concise, diastereoselective synthesis of (+/-)-fumagillol (3) and formal, enantioselective syntheses of the potent angiogenesis inhibitors fumagillin (1) and TNP-470 (2) are reported. The origin of asymmetry is a highly diastereoselective Diels-Alder reaction using a diene with a chiral oxazolidinone auxiliary. The stereochemical course of a key conjugate addition reaction is controlled by the cup-shaped architecture of a cis-fused bicyclic enal. Other key steps include a facile hetero-Claisen rearrangement and a site-selective Sharpless epoxidation.