Found Active Compounds Based On Multiple Strategies And The Synthetic Methods Of Two Privileged Structures

There are two parts in my dissertation. Part1, multiple strategies used in active compounds discovery. This part have carried out three aspects of research work:found DPP-IV inhibitors based on virtual screening, found antibacterial activity compounds based on the old drugs and found anti-inflammatory compounds based on the natural products. Meanwhile, we have completed the synthetic work of Moracin C, Moracin M and Artoindonesianin B-1. Our synthetic strategy including three routes, and one of these routes can obtain the natural products Moracin C, Moracin M and Artoindonesianin B-1. By optimizing the reaction yield, the overall yields are43%of Moracin C,59%of Moracin M and11%of Artoindonesianin B-1. Compared with the existing reported results, we greatly improved the total yields of Moracin C and Moracin M, and the total synthesis of Artoindonesianin B-1is the first time report by this dissertation.Part2, the synthesis methods of two privileged structures. This part developed the synthesis methods on1,3-dihydro-3-aryl-3-hydroxy-indol-2-one compounds and α,β-dihydroamino acids. The structure1,3-dihydro-3-aryl-3-hydroxy-indol-2-one is an privileged structure widely in natural products. In recent years, there are many reports on the synthesis of this kind of structures. However, we implemented an asymmetric catalytic Friedel-Crafts alkylation reaction, through one step get the privileged structure of1,3-dihydro-3-aryl-3-hydroxy-indol-2-one. Uniformly good yields (42-83%) and good ee values (70-94%) are obtained for all cases studied, and groups with different substitution patterns are well tolerated and lead to the structurally diverse compounds. The biological activity of these compounds is ongoing in our laboratory. α,β-Dihydroamino acids is a kind of very important compounds in drug discovery, widely exist in bioactive peptides. And we designed a Mannich-elimination cascade reaction to get the α,β-dihydroamino acid esters. The reaction works in one step with good yields (51-98%). And through simple chemical conversions on a,P-dihydroamino acids can get the (R)-γ-oxo-α-amino acids respectively.