Semi-synthesis Of The Side Chain Of Tibepine Pivoxil And Saponin VI

Bacterial resistance becomes more and more enhanced in the world,the research and development of activity antibiotics is an effective means to solve this serious problem.In recent years,carbapenems become hot topics in this field.So far,there are seven varieties in the carbapenems market.They are mipenem,panipenem,meropenem,biapenem,ertapenem,doripenem and tebipenem pivoxil,respectively.Compared with similar drugs,tebipenem pivoxil,a novel oral carbapenem antibacterial drug,is used to treat children infectedotitis media,sinusitis and pneumonia,et al.Pennogenin saponins are one of the active ingredient of polyphylla,belonging to 17-hydroxyl steroid compounds,a significant biologically active steroidal saponins,it can inhibit gastric mucosal injury,uterine bleeding,platelet aggregation,and have anti-bacterial and anti-cancer biological activities.They can be obtained by the extraction and separation,chemical synthesis,biotransformation,but all can not obtain an effective breakthrough.In the synthetic methods of tebipenem pivoxil,the research of its side chain is very important.Further,since the pennogenin saponins have good biological activities,but polyphylla natural resources is extremely limited.So the synthesis of side chain of tebipenem pivoxil and pennogenin saponins VI are the main research contents of this paper.In chapter one,the research status of carbapenem and pennogenin saponins are reviewed.In Chapter two,compound FM-d could be synthesized by compound 52 and 53 under alkaline condition.Then compound FM-e was got by MsCl protection of FM-d.FM-e reacted with AcSK to give FM-f.The final production 1 was synthesized from FM-f by hydrolysis reaction in the KOH/methanol solution and salt-forming reaction with HCl/methanol solution.In Chapter three,the pennogenin saponin VI was synthesized by using glycosylation.In these reactions the difference of steric hindrance between 3-OH and 17-OH of pennogenin was utilized skillfully and only 3-OH of pennogenin could be connected with each kind of donors selectively and there was no reaction at 17-OH which was not protected.Finally,the structures of all the intermediates as well as target compounds were confirmed by 1H-NMR and 13C-NMR spectrometer and the market prospects were discussed.