FACILE SYNTHESIS OF A SIMPLIFIED BICYCLO[7.3.1] ESPERAMICIN-CALICHEAMICIN ENEDIYNE CORE

An efficient non cobalt mediated route for the synthesis of a simplified bicycle [7.3.1]enediyne core of the naturally occurring calicheamicins and esperamicins is described. The key cyclization provides a single propargylic alcohol stereoisomer which is in the same relative configuration as that found in the naturally occurring calicheamicins and esperamicins. Selective functionalizations of the cyclized core via selenium dioxide oxidations are described. Installation of an enone chemical trigger provides a hydroxylated analog of a previously described biologically active synthetic enediyne.