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1、第二军医大学博士学位论文中药金铁锁的系统化学成分研究姓名：田均勉申请学位级别：博士专业：@指导教师：张卫东2011-06
第二军医大学博士学位论文性的测试。在分析环肽tunicyclinA(1)生源合成途径的过程中，发现tunicyclinE(5)可能是tunicyclinA(1)的生源前体。通过化学反应验证发现，环肽tunicyclinA(1)可以由环肽tunicyclinE(5)经过光敏氧化反应直接得到。基于该反应，我们推测了由tunicyclinE生成tunicyclinA可能的反应途径。本论文还对所分
2、离到的环肽进行了抗真菌活性测试，并且发现tunicyclinD(2)具有强效广谱的抗真菌活性，对热带念珠菌（Candidatropicalis）的MIC80值可达到0.25μg·mL。对金铁锁的总皂苷也进行了抗炎活性测试，发现总皂苷在60μg/ml的浓度-1下对NO的抑制率为66.5%，目前正在进一步的研究总皂苷的免疫活性和抗炎活性。本论文还对中药的抗炎活性成分的作用机制进行了综述。关键词：金铁锁，三萜皂苷，环肽，构象分析，结构修饰，抗真菌活性，免疫活性-2-
中药金铁锁的系统化学成分研究AbstractPs
3、ammosilenetunicoidesW.C.Wuet.C.Y.Wu,amonotypegenusplantofCaryophyllaceacefamily,isawell-knownmedicinalherbusedasanodyneandhaemastaticagentinsouthwestChina.ThisdissertaiondescribesthechemicalconstituentsandbioactivitystudyofP.tunicoides.Inaddition,someofcomp
4、oundsfromthetitledspeciesweremodifiedandtestedfortheirbioactivities.1.ThechemicalconstituentsofPsammosilenetunicoides80chemicalconstituents,includingcyclicpeptides(1~11),triterpenoidsaponins(12~29),carbolines(30~35),maltolglycosides(36~51),lignans(52~58),an
5、dothercompounds(59~80)wereisolatiedfromP.tunicoides.Thestructuresof79compoundswereelucidatedonthebasisofspectroscopicstudies.44compoudswereindentifiedasnewcompouds.Compound1(tunicyclinA)isthefirsttricycliccyclopeptidewithauniquetricyclicringcyclopeptideskel
6、etonfromhigherplant.Thestructureofadiketopyrrolo[1,2-a]pyrazineincompound1(tunicyclinA)istotallynewinthepeptidesarea.Furthermore,bothcompound4(tunicyclinB)andcompound10(tunicyclinI)containunusualα,β-dehydrotryptophan(ΔZ-Trp)residues，previouslyreportedonlyfr
7、ommarinespongeandbacteria.2.TheconformationanalysisoftunicyclinE(5)andtheintramolecularcatalysisofcis/transisomerizationofpeptidyl-prolylbondCompound5(tunicyclinE)existsintwoconformations(5a,trans;5b,cis)insolutionthatderivefromrestrictedrotationoftheSer7-P
8、ro1peptidebond,whileonlytransSer7-Pro1conformationisfoundincrystalstate.Toexplorethemolecularbasisoftwoconformationsof5insolutionandtheirinterconversionmechanism,X-raydiffraction,NMRexperiments,andtheo
