Flow chemistry in the multi-step synthesis of natural products

The total synthesis of natural products is constantly facing many challenges derived from the complexed chemical structures, the lengthy synthetic routes, the time-consuming workup procedures and the large environmental footprint. In the past two decades, performing chemical transformations in continuous flow using various types of microreactors and in-line auxiliary technologies have been demonstrated effectively in respects of enhanced reaction yield and selectivity, excellent reproducibility and easy scale-up, safe proceeding hazardous reaction. And the rapid synthesis of natural products, which has been enabled in continuous flow based upon the significant improvement of overall yield within a short residence time via processing intensification and systematic automation, is essential to furnish sufficient quantity for the bioactivity investigation of structural diversity modification, structure-activity relationship during drug discovery and the increasing consumption of medical treatment. In this review, the multi-step continuous flow synthesis of natural products is highlighted to provide a comprehensive recognization on the intrinsic merits of flow chemistry for organic chemists to purposefully develop the flow synthetic approaches of natural products in the future.