Unified, Catalyst-Controlled, Bioinspired Total Synthesis of Dimeric Piperine Alkaloids in Batch and Flow †

Abstract

We report a unified, bioinspired total synthesis of nigramide R, chabamide, and dipiperamide F and G enabled by catalyst-controlled photocatalytic dimerization of piperine. Selective [2+2] or [4+2] cycloadditions proceed in both batch and continuous flow, providing divergent access to multiple dimeric alkaloid frameworks from a common precursor. To overcome prolonged irradiation times and substrate photodegradation, we developed a standardized, low-cost, 3D-printed continuous-flow PhotoFlow reactor platform, enabling enhanced efficiency and reproducibility. This work establishes a modular and general strategy for streamlined access to structurally diverse dimeric alkaloids.