A New Approach to the Synthesis of the Bicyclic Core of the Immunosuppressants SNF4435 C & SNF4435 D via Silicon Tethering

Abstract

The total synthesis of immunosuppressant and multidrug resistant (MDR) reversal agents SNF4435 C and SNF4435 D, isolated from the culture broth of an Okinawan strain of Streptomyces spectabilis in 2001, has been accomplished in a fourteen step process. The key reaction utilizes a Stille coupling en route to the final products. Considering the limitations of the Stille coupling, we are currently adjusting the procedure to allow for a new approach, which involves the use of a molecular tether to join the two precursor molecules. This thesis describes the synthesis of a new pair of precursors as well as our efforts toward linking said molecules together via an appropriate silicon bridge.