Synthesis of theNatural Product Berberine

In this work, the synthesis of berberine was accomplished through three distinct routes. The key innovation lies in replacing the traditional intermediate piperonylamine with 2,3-dimethoxybenzylamine, thereby circumventing the lengthy and low-yielding steps of the intermediate. The newly developed routes are characterized by short synthetic sequences and by overall yields of 22.6–32.8% for berberine. Moreover, the starting materials are inexpensive, readily available, and derived from natural sources. Notably, in contrast to previously reported routes, route 2 can be carried out entirely at ambient temperature under atmospheric pressure. These attributes position the developed routes as candidates for industrial scale-up.