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.