COMMUNICATION pubs.acs.org/JACS Enantioselective Total Synthesis of ()-Acetylaranotin, a

ABSTRACT: The first total synthesis of the dihydroox-epine-containing epidithiodiketopiperazine (ETP) ()-acetylaranotin (1) is reported. The key steps of the synthesis include an enantioselective azomethine ylide (1,3)-dipolar cycloaddition reaction to set the absolute and relative stereochemistry, a rhodium-catalyzed cycloi-somerization/chloride elimination sequence to generate the dihydrooxepine moiety, and a stereoretentive dike-topiperazine sulfenylation to install the epidisulfide. This synthesis provides access to ()-1 in 18 steps from inexpensive, commercially available starting materials. We anticipate that the approach described herein will serve as a general strategy for the synthesis of additional members of the dihydrooxepine ETP family. The epidithiodiketopiperazine (ETP) natural products are alarge and structurally diverse family of biologically activ