Stereoselective Synthesis of Benzoylated Gulmirecin A and Disciformycin B

Disciformycins and gulmirecins are potent inhibitors of the bacterial RNA polymerase. They show promising activities against multidrug-resistant pathogens often found in clinical settings, such as methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA). Our modular, high-yielding, and scalable synthetic approach started with the desymmetrization of divinyl carbinol and provided benzoylated precursors for both natural product classes. The 12-membered macrocycle was assembled by a stereoselective Nozaki–Hiyama–Takai–Kishi macrocyclization.