Studies on a Type III Atropisomeric Colchicine Analog Enabled through an Intermolecular Oxidopyrylium (5 + 2) Cycloaddition/Reductive Ring-Opening Sequence

Lauren P. Bejcek, Orugbani S. Eli, Anastasiya Lyubimova, Diana M. Kapkayeva, Jordan Nafie, John A. Beutler, Emilio Gallicchio, Dan L. Sackett, Ryan P. Murelli

Colchicine is one of the oldest known microtubule-targeNng agents, and the development of clinically viable colchicine binding site inhibitors (CBSIs) remains of high interest to the medicinal chemistry community. Colchicine’s binding to tubulin is the result of its biaryl methoxytropone-trimethoxybenzene system (called the AC ring), which binds in a preferred aR conformation.

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