Modular and Divergent Syntheses of Protoberberine and Protonitidine Alkaloids

A modularly convergent and divergent strategy was established for the family synthesis of both protoberberine and protonitidine alkaloids. The robust, scalable, and flexible synthetic route featured a collective preparation of protoberberine and protonitidine alkaloids from a common isoquinoline assembled from pyridyne as the key synthon, which was based on the selective N-C or C-C cyclization via distinct processes. Through the strategy, 20 protoberberine alkaloids, 5 protonitidine alkaloids, and 11 analogues with diverse substituents were comprehensively aquired.