Synthetic Preparation of the Macrocyclolipopeptide Dysoxylactam A for Potent P-glycoprotein Inhibition

In 2019, the cyclolipopeptide dysoxylactam A was isolated and reported to be a potent inhibitor of the drug efflux pump P-glycoprotein and demonstrated the ability to reverse multidrug resistance in cancer cell lines. Herein, we report a reliable and flexible route toward dysoxylactam A, which features key transformations such as the Paterson 1,2-<i>anti</i> aldol reaction, an sp³-sp³ Fu-Suzuki coupling, asymmetric allylation, and the Corey-Nicolaou macrolactonization. All the data obtained on the synthesized natural product matched those of the authentic material.