The sorbicillinoid family is a large class of natural products known for their structural variety and strong, diverse biological activities. A special member of this family, sorbicillactone A, the first nitrogen-containing sorbicillinoid, exhibits potent anti-leukemic and anti-HIV activities and possesses a unique structure formed from sorbicillinol, alanine, and fumaric acid building blocks. To facilitate in-depth biological and structure-activity relationship studies of this promising natural product, we developed a chemoenzymatic approach that provides access to sorbicillactone A and several analogs with excellent yields under precise stereochemical control. The key steps of the highly convergent, stereoselective, and short route are the enantioselective oxidative dearomatization of sorbillin to sorbicillinol catalyzed by the enzyme SorbC and the subsequent Michael addition of a fumarylazlactone building block. Additionally, our synthetic findings and bioinformatic analysis suggest that sorbicillactone A is biosynthetically formed analogously.