Synthesis Of Quinolone Derivatives

Due to the abuse of antibiotics,the resistance of bacteria has become a serious problem in the clinical practice of antimicrobial chemotherapy,so the development of effective drugs for infection caused by bacteria is urgently desired.The rapid development of quinolones makes them the most commonly used antibacterial drugs in clinical practice.Tetrahydropyrrolidine derivatives as a kind of special structure widely exist in various natural products.In synthetic drugs,pyrrolidine derivatives play an extremely important role.Quinolones are synthetic organic compounds with 4-oxo-1,4-dihydroquinoline-3-carboxylic acid as the core structure.According to the antibacterial structure-activity relationship of quinolone derivatives,this article designes the introduction of different3-aminopyrrolidines at the C7 position of fluoroquinolone to synthesize fluoroquinolone derivatives.A variety of blocks containing pyrrolidine structure were synthesized by the[3+2]cycloaddition reaction of N-benzylmethimine ylide and olefin derivatives.N-Bn of this series of blocks was converted into N-Cbz,3-COOR was saponified to 3-COOH,and3-COOH was converted by Curtius rearrangement to 3-NHBoc.Azabicyclo[3,1,0]hexane was synthesized by 4-carbonyl-pyrrolidine derivatives as starting material.After reduction and elimination to form double bonds,the Corey-Chaykoveky reaction finally occurs to build cyclopropaneg.Finally,the synthesized various 3-NHBoc pyrrolidine building blocks were hydrogenolyzed to remove the benzyloxycarbonyl group and then reacted with the fluoroquinolone intermediate through coupling and hydrochloric acid deprotection to form hydrochloride to synthesize ten fluoroquinolone derivatives.The structure of target products were characterized by ¹H NMR,¹³C NMR and mass spectrometry,and the antibacterial activity of the target compounds against Escherichia coli,Staphylococcus aureus and Micrococcus tetragenus was determined.The results showed that the ten target compounds have good antibacterial activity against the three tested bacteria.