Sulfur Ylide-Mediated Cascade Transformations to Access Cyclopropylallocolchicinoids with Potent Antimitotic Activity

We present an efficient one-pot transformation for the synthesis of unprecedented classes of cyclopropyl-fused allocolchicinoids through the discovery of a new reactivity pattern of sulfoxonium ylides. This hybrid strategy rationally manipulates the nucleophilic character of sulfur ylides to achieve the regio- and stereoselective construction of structurally intriguing allocolchicinoids bearing multiple stereocenters. Notably, this methodology represents the first general approach to sp³-rich dibenzocycloheptanes, including enantiomerically enriched variants. Furthermore, we have demonstrated the synthetic utility of this protocol in preparing various advanced intermediates pertinent to natural product synthesis and medicinal chemistry. Comprehensive biological studies have identified a potent analogue that disrupts microtubule organization and dynamics, leading to mitotic arrest and the consequent attenuation of influenza A virus infection.