Synthesis of (S,S)‐Diisotyrosine and Its Incorporation in an Ansa Tripeptide

The characteristic building block of the strongly antibacterial ansa tripeptides WS-43078 A and B is diisotyrosine 1. Etherated 1, containing four differentiated amino and carboxy protecting groups, could be obtained by stepwise enantioselective and diastereoselective synthesis (ee and de > 99 %). The ansa tripeptide 2 was synthesized as model of the natural product. The ring closure was accomplished in 80 % yield via the linear pentafluorophenyl ester — independently of on which “side” the additional amino acid had been incorporated.