Synthetic studies related to MPC1001: formation of a model epidithiodiketopiperazine

A tricyclic epidithiodiketopiperazine was prepared having structural features related to the antitumor antibiotic MPC1001. The method is based on the use of the sulfenylating agent p-MeC6H4S(O2)SCH2OSiMe2Bu-t to introduce two protected sulfur atoms in a sequential and stereocontrolled manner. Fluoride-induced deprotection to remove the CH2OSiMe2Bu-t units and release two sulfhydryl groups, followed by in situ oxidation, then generated the required bridged disulfide.