Here, we present a 6-step gram-scale synthesis of (±)-gregatin A, a fungal polyketide characterized by an alkylated furanone core origi-nally isolated from Cephalosporium gregatum. The synthetic route features an intermolecular 1,3-dipolar cycloaddition, a Mo-mediated disconnection of isoxazole skeleton, and an acid-mediated desilylation/enamine hydrolysis and hemiketalization cascade. Notably, this synthetic approach establishes a versatile platform applicable to the synthesis of diverse gregatin congeners, allowing for the introduc-tion of varied side chains. Our method not only facilitates the scalable production of (±)-gregatin A but also opens avenues for the ex-ploration of structural analogs with unique biological activities.