Synthesis and Biological Activity of Enantiomers of Antitumor Irofulven

Stereoselective synthesis of (-)-irofulven has been achieved by cycloaddition of (R)-5-chloro-5-methyl-2-cyclopentenone to the 1,3-dipolar intermediate from 1-acetyl-1-(diazoacetyl)cyclopropane. The enantiomer, (+)-irofulven, was prepared in a similar way starting with (S)-5-chloro-5-methyl-2-cyclopentenone. (+)-Irofulven was 5 to 6 times less toxic than (-)-irofulven to adenocarcinoma (MV 522) cells.