Total Synthesis of (−)-Tetrazomine. Determination of the Stereochemistry of Tetrazomine and the Synthesis and Biological Activity of Tetrazomine Analogues

The first total synthesis of the potent antitumor antibiotic (−)-tetrazomine has been accomplished. A new method for the formation of the allylic amine precursor to an azomethine ylide has been developed and exploited in an efficient [1,3]-dipolar cycloaddition to afford the key tetracyclic intermediate used in the synthesis of (−)-tetrazomine. Several analogues of tetrazomine have been synthesized and tested for antimicrobial and biochemical activity.