Copper Catalysis, Organic Catalysis Research Methodology And Double Benzyl Four Hydrogen Isoquinoline Alkaloid Synthesis And Structure-activity Relationship Study

This paper is divided into two parts, the methodology section and the medicinal chemistry section.In the methodology section,3-Alkyl isocoumarins are provided by CuI/amino acid-catalyzed Sonogashira coupling reaction of o-bromo benzoic acids and terminal alkynes and the subsequent additive cyclization. This cascade process allows synthesis of diverse isocoumarins by varying both coupling partners bearing a wide range of functional groups.The combination of O-TMS protected diphenyl-prolinol and benzoic acid was found to be effective to catalyze the Michael addition of aldehydes to3-substituted3-nitroacrylates. The reaction provided syn,anti-Michael adducts with good diastereoselectivity and excellent enantioselectivity. Some-aryl and-methyl substituted nitroolefins also worked under these conditions, although they need prolonging reaction time. These adducts could be used for assembling2,3,4-trisubstituted pyrrolidines through simple hydrogenation.In the medicinal chemistry section, the bisbenzylisoquinoline(BBI) alkaloids are among the hottest races in pharmaceutical development. In this paper we focused on the structure, function of BBI alkaloids, and advance of their activities.25novel BBI alkaloids were synthesized and their structures were confirmed by’H-NMR and ESI-MS. The anti-tumor activities of25novel compounds were tested by the MTT method in vitro against two cancer cell lines (A431and A549), with B037as the positive control.15compounds exhibited potent anti-tumor activity. IC50values ranging from1.06to45.15μM. Among them, compound W-23showed the best activity in potent anti-tumor activity. The preliminary structure-activity relationship of the compounds were discussed.