A Natural Product Inspired Tetrahydropyran Collection Yields Mitosis Modulators that Synergistically Target CSE1L and Tubulin

A Prins cyclization between a polymer-bound aldehyde and a homoallylic alcohol served as the key step in the synthesis of tetrahydropyran derivatives. A phenotypic screen led to the identification of compounds that inhibit mitosis (as seen by the accumulation of round cells with condensed DNA and membrane blebs). These compounds were termed tubulexins as they target the CSE1L protein and the vinca alkaloid binding site of tubulin.