Asymmetric Total Synthesis of (−)‐Glycybridin B, a Pharmacophore Screened Candidate for Tubulin Binding

Microtubule-targeting agents (MTAs) represent a pivotal class of therapeutic compounds designed to disrupt microtubule dynamics, leading to cell cycle arrest and apoptosis in malignant cells. Nevertheless, their off-target effects on healthy, rapidly dividing cells result in significant neurotoxicity and myelosuppression. Ongoing research aims to enhance their specificity and identify novel active scaffolds to minimize adverse effects and fight drug resistance. Searching for new potential tubulin binders with a pharmacophore screening method, we identified glycybridin B as a promising natural product. Here, we report the first total synthesis of this compound via a five-step route, involving a key chalcone intermediate, along with its biological evaluation.