Enantioselective Total Syntheses of (−)-FR901483 and (+)-8-<i>epi</i>-FR901483

The enantioselective total syntheses of the potent immunosuppressant FR901483 (<b>1</b>) and its 8-epimer (<b>47</b>) have been accomplished. Our approach features the use of building block <b>6</b> as the chiron, the application of the one-pot amide reductive bis-alkylation method to construct the chiral aza-quaternary center (dr = 9:1), regio- and diastereoselective intramolecular aldol reaction to build the bridged ring, and RCM to form the 3-pyrrolin-2-one ring