Progress Toward the Total Synthesis of Paecilospirone

Abstract

Progress towards the total synthesis of paecilospirone, a microtubule inhibiting natural product, is reported. The stereochemical outcome of the proposed steps has been verified by both a computational study and the synthesis of a model system. The synthesis incorporates the use of modern methods, including organocatalytic cyclization, palladium- and nickel-catalyzed crosscouplings, and oxidative spiroketalization. The use of these methods allows for the more modular, efficient, and sustainable synthesis of a potentially valuable antitumor compound. Additionally, the incorporation of novel methods in the synthesis of a complex target demonstrates the limitations and benefits of these modern transformations, and will serve to inform their use in future syntheses.