The welwitindolinone class of natural products were recently isolated from cyano-bacterial sources and show promise for the treatment of multi-drug resistant tumor cells. Some members of this class of compounds exhibit chemoresistance reversing activities below toxic doses. Other members, including welwistatin, are cytotoxic agents which act by inhibiting microtuble formation in both drug sensitive and multi- drug resistance tumor cells. This proposal outlines an enantioselective synthesis of welwistatin as a representative member of this class of compounds exhibit chemoresistance reversing activities below toxic doses. Other members, including welwistatin, are cytotoxic agents which act by inhibiting microtuble formation in both drug sensitive and multi- drug resistance tumor cells. This proposal outlines an enantioselective synthesis of welwistatin as a representative member of this class of compounds. The key step in the synthesis is a novel Lewis acid catalyzed enamine cyclization-Pinacol rearrangement which simultaneously assembles the bicyclic core and installs the critical quaternary bridgehead center.
