Studies in multidrug resistance reversal: a rapid and stereoselective synthesis of the dihydroagarofuran ring system

Several dihydroagarofuran esters have been reported to be effective multidrug resistance (MDR) reversing agents for both cancer cells and bacteria. We report a rapid synthesis of the dihydroagarofuran ring system from carvone in a sequence that is highlighted by a sequential conjugate addition/aldol sequence, a ring closing metathesis reaction, and a diastereoselective alkene reduction to provide an axial methyl group. The synthesis allows for differential esterification reactions as required to study the roles of these groups in MDR reversal.