Total Synthesis of (±)-Prostratin

Natural molecules have been continuously offering drug leads for treatment of human diseases. However, searching for the optimal drugs can be often challenging because of the complexity of structural modifications. In this regard, efficient and flexible chemical synthesis routes to the relevant molecules can provide unparalleled opportunities. Prostratin and its structural relatives are complex plant-derived molecules that have shown diverse potential as drug candidates. Prostratin itself is a promising lead for developing a long-sought-after cure for human immunodeficiency virus (HIV) infection and an anti-cancer drug. In this work, we report a short and modular synthetic route to prostratin from very simple chemicals. Because of its high efficiency and flexibility, this route enables full structural optimization of the molecule and also provides a chemical foundation for exploring its derivatives' potential as medical agents.