The Synthesis Of Quinolines And Oxadiazole Derivatives And The Study On The Inclusion Behavior Of Yellow Rattan And Cyclodextrin

The compounds containing the parent nucleus structure of quinolone and quinazoline ordinarily have the physiological activity of antimalarial,anticancer,anti-nflammatory,anti-hypertension and analgesia etc.Many drugs,such as quinine,camptothecin,gefitinib,lapatinib and erlotinib,contain quinoline or quinazoline parent nucleus structure.1,2,4-Oxadiazole derivatives possess antibacterial,analgesic,antispasmodic,antihypertensive and anti-inflammatory biological activities,which are often used as pharmacophore in the design of new drugs.Therefore,the search of new methods for the synthesis of heterocyclic compounds has great significance for new drug research and investigation.Fibrauretine has antibacterial,anti-inflammatory,anti-virus,immunomodulation and other biological activity,which was known as plant antibiotics.It needs high-dose and long-termclinical administration to ensure the curative effect for the poor absorption in the gastrointestinal tract of fibrauretine,which limits the clinical promotion of fibrauretine.Cyclodextrin,a multi-functional pharmaceutical adjuvant,can significantly improve the physic-chemical properties and bioavailability of drug through the inclusion of the drug.This paper mainly carried on the following three aspects of research work:Part 1:A series of 2-(2-aryl-4-substituted quinoline)-ethyl-1-tightening alcohols was synthesized by three-component "one pot" method.The reactions applied simple and readily available aromatic amines,aromatic aldehydes and propargyl alcohol as raw materials,which reacted under CuCl and AuCl3 as catalysts in tetrahydrofuran.This has laid a good foundation for diversified substitution synthesis of 4-substituted quinolone derivatives.17 compounds were synthesized by this method,and the yield was 72%-95%.Part 2:Based on the parent nucleus structure of quinolone, a serics of novel and diverse heterocyclic compounds containing 1,2,4-Oxadiazole bicyclic structure were synthesized. The reactions applied ?-chlorobenzaldoxime as synthons, and the yield was 70%~91%. The biological activity of these compounds will be tested, and it is expected that there will be a better pharmacological activity.The structures of above two kinds of compounds were characterized by 1H NMR,13C NMR IR and HRMS,and the characteristic structure was confirmed by X-Ray single crystal diffraction.Part 3:A series of inclusion complexes was prepared by fibraurctine and cyclodextrins.The complexation between host and guest was characterized and confirmed by NMR,FT-IR, UV-vis, XRD, TG, SEM and other methods. Stability experiments showed thatinclusion complexes were more stable than fibrauretine in a normal environment, which guaranteed a lower storage cost. And the decomposition rate and ratio of inclusioncompounds and fibrauretine were similar in the acidic environment, which ensured the gastrointestinal absorption of active ingredients. The research results will providescientific basis for the study of new formulation of the fibrauretin.