Total Synthesis Of Berberine And Nitidine And Studies On The Structure-activity Relationship Of Berberine

Small molecules can regulate the metabolism process of life through controlling the process of gene expression and enzyme catalysis.The alkaloids have attracted intense attentions of many chemists due to their diverse structures and the potent biological activities such as anti-inflammatory,antibacterial,anticancer and so on.In addition,many of them are used for pharmaceutical and pesticides.Our group's research focuses on total synthesis driven by methodology development.We hope to find a general solutions to common skeleton of a group of alkaloids,and apply them to the synthesis of natural products.Concise total synthese of two kinds of quaternary ammonium type alkaloid is described,featureing an oxidative suzuki reaction and a selective 6?-electrocyclization reaction.We can synthesize two coupling precursors from same commercially available benzyl alcohol either via a bromination reaction followed by an oxidation reaction or an oxidation reaction followed by an Ohira-Bestmann reaction.A Sonogashira coupling of two fragments and subsequent silver catalysis cyclization reaction afforded a series of 3-arylisoquinoline.Through C-H activation vinylation and 6?-electrocyclization,we synthesized either berberine-like or nitidine-like alkaloids.We will test their anticancer bioactivitiesThere are many advantages in our strategy.Firstly,there is no need to remove the directing group in our synthesis,while it often takes many steps to remove directing groups in general C-H activation reaction.Secondly,we can synthesized two kinds of alkaloids by controling the reaction conditions of 6n electrocyclization.In summary,we have developed a modular,convergent synthetic strategy for berberine and nitidine natural products.