Design And Synthesis Of Arctigenin Derivatives As The Prodrugs Of Anti- Alzheimer’s Disease And C-N Coupling Reaction Catalyzed By CuI/Metformin

This thesis consists of two parts:(1) design and synthesis of arctigenin derivatives as the prodrugs of anti-Alzheimer’s disease; (2) C-N coupling reaction catalyzed by Cul/metformin.Alzheimer’s disease is a kind of progressive neural degenerative disease. Aβ protein deposition hypothesis is the main pathogenesis. Arctigenin, isolated from traditional Chinese medicine fructus arctii, can reduce Aβ and play the role of resistance to the AD. However, both the solubility and bioavailability are low. In order to improve the water-soluble and oral bioavailability, we design, synthesis and obtain 13 compounds as prodrugs. Among them, compound A5, the nature of all aspects are better, oral bioavailability is 25.6%.Ullman-type C-N coupling reaction is a convenient and versatile method for the construction of C-N bond, and is widely used in organic synthesis. This paper provides a facile and efficient method for C-N coupling reaction catalyzed by Cul/metformin. The advantages of this method are the use of an inexpensive and readily available catalyst and ligand, easy workup, shorter reaction time and improved yields. Furthermore, this procedure is applied successfully for the modification of natural products, such as Vindoline and Tabersonin.