Heterogeneous Cu Catalyzed Reaction And Their Applications In The Synthesis Of Pharmaceutical

In the process of drug development,the construction of the compound library plays a very important role in drug screening and structure activity relationship studies.New chemical technologies and methods provide a guarantee for the rapid construction of compound librariy.Catalytic reaction,which can easily complete the modification of drug molecules and synthesis of API for clinical studies,is one of the important means to realize this goal.Copper catalyst shows some interesting advantages over other metals,such as cheap and low toxicity to organism,especially the supported copper catalyst which is recoverable easily and reusable.In this paper,two kinds of polysaccharide supported copper catalysts were prepared,and the following work was carried out:1.Cellulose supported nano copper catalyst was prepared and characterized by XPS,TEM and ICP-AES.This heterogeneous catalyst was used for the synthesis of N-glycosyl-1,2,3-triazoles from glycosyl azides and alkynes.The catalytic reaction was performed in water,and no external ligand or base was required.The cellulose@Cu catalysts in this catalytic system are easily recoverable and efficiently reusable,which proved to be a simple,efficient and environment friendly heterogeneous catalyst.15 glycosyl trizaloes and 5 quinolone-AZT conjugate were synthesized using this method.It provides an effective protocol for the glycosyl azides library biulding.2.The chitosan@copper catalyst was prepared and characterized by XRD,TEM,IR,TG and ICP-AES?The heterogeneous catalyst was then applied to the C-S coupling reaction.The chitosan@copper catalyst catalyzed the coupling reactions of aryl halides with sodium sulfonates,and the corresponding sulfones were obtained in good to excellent yields.The highly active catalyst can be reused many times without losing its catalytic activity.In addition,by using this protocol,the marketed anti-ulcer drug zolimidine(antiulcer)could be synthesized easily.3.A series of novel carbohydrate-derived Erlotinib derivatives were prepared by the copper catalyzed cycloaddition reaction of erlotinib with various azido-sugars.These newly synthesized compounds were characterized and their cytostatic effects evaluated in vitro on MDA-MB-231,HEPG-2,A549,and MCF-7 human cancer cell lines using an MTS assay.Compared with erlotinib,the carbohydrate-derived derivatives had the expected inhibitory effects on MDA-MB-231 and HEPG-2 cell llines.The results of molecular docking study showed that some of the compounds could bind to EGFR and HER2.These studies lay a foundation for the further development of 4-anilino quinazoline derivatives for the antitumor agents.