酚酸衍生物之合成及其生物活性之研究

ISynthesisandBiologicalActivitiesofPhenolicAcidsDerivatives(Ya-TingLee)(Li-KangHo)(Chieh-FuChen)NationalYangMingUniversityInstituteofPharmacologyDoctorThesisDecember2004IIIII-喜悦與您們共享IVIIIIVIVIIIXIIXVXVII..--------------------------------------------------------------01.--------------------------------------------------------------01.--------------------------------------------02.(C6-C3)-----------------03.--------------------------------------------------------04.--------------------------------------------------05.-----------------------------------------06..--------------------------------------------------------12.--------------------------------------------------------14V.----------------------------------------------------------15.------------------------------------------------24.------------------------------------------------26..--------------------------------------------------------281.-----------------------------------------------------282.-----------------------------------------------293.-----------------------------344.3-pyridin-3-yl-acrylamides--------------------------415.3,4-methylenedioxy-cinnamicacidamides-------45.-----------------------------------------------47..-----------------------------------------------69.-----------------------------------------------------69.--------------------------------------------------------72.-----------------------------------------------------------------74.---------------------------------------------------------75.---------------------------------------------------------------82.---------------------------------------------------------------92VI--------------------------------------------------------------------94-------------------------------------------------------------------111-------------------------------------------------------------121----------------------------------------------------------------150VII1-1.PA01-PA151-2.PA01-PA152-1.2a-2g2-2.3a-3e2-3.pyridinyl4a-4d2-4.3,4-methylenedioxy2-5.6a-6n3-1.3-2.PA01-PA15DPPH3-3.3a-3eDPPH3-4.DPPH3-5.PA01-PA153-6.PA01-PA15PMA-fMLP-3-7.PMA-fMLP-VIII3-8.2a-2g3-9.3-10.pyridinyl4a-4d3-11.3,4-methylenedioxy5a-5c3-12.6a-6n3-13.PMA-fMLP-IC503-14.SAS,OEC-M1MCF-7IC50IX1-1.1-2.-1-3.1-4.2-1.(U.V.450WIMMER.LampOperation)2-2.DPPH2-3.Xanthinesuperoxide2-4.PMA-fMLP-3-1.PA01,PA04,PA07PA11DPPH3-2.PMA-3-3.fMLP-3-4.MTT6a,6c,6h,6kCAPESAS3-5.MTT6a,6b,6c,6hCAPEOEC-M1X3-6.MTT6a,6b,6c,6kCAPENHOF3-7.6a,6b,6cCAPESAS3-8.OEC-M13-9.6b(25or50µM)OEC-M14-1.N-cis-feruloyl3-methyldopamine(1a)NMR4-2.N-trans-feruloyltyramine(2a)NMR4-3.N-trans-caffeoyltyramine(2d)NMR4-4.N-trans-caffeoyltyramine(2d)NMR4-5.6-fluoroveratraldehydeNMR4-6.6-FluoroveratraldehydeNMR4-7.1-(2-fluoro-4,5-dimethoxyphenyl)2-nitroethyleneNMR4-8.1-(2-fluoro-4,5-dimethoxyphenyl)2-nitroethyleneNMR4-9.2-(2-fluoro-4,5-dimethoxyphenyl)ethylamineNMRXI4-10.2-(2-fluoro-4,5-dimethoxyphenyl)ethylamineNMR4-11.2-fluorodopamineNMR4-12.2-fluorodopamineNMR4-13.N-[2-(2-fluoro-4,5-dimethoxyphenyl)ethyl]-3-(4-hydroxy-3-methoxyphenyl)acrylamide(3a)NMR4-14.N-[2-(2-fluoro-4,5-dimethoxyphenyl)ethyl]-3-(4-hydroxy-3-methoxyphenyl)acrylamide(3a)NMR4-15.N-[2-(2-fluoro-4,5-dimethoxyphenyl)ethyl]-3-(4-hydroxy-3-methoxyphenyl)acrylamide(3a)NMR(HMBC)4-16.N-[2-(4-hydroxyphenethyl]3-pyridin-3-yl-acrylamide(4c)NMR4-17.N-[2-(4-hydroxy-phenethyl]-3-pyridin-3-yl-acrylamide(4c)NMR4-18.3,4-methylenedioxycinnamoyltyramine(5c)NMR4-19.3,4-methylene-dioxycinnamoyltyramine(5c)NMR4-20.3-(4-methoxyphenyl)acrylicacid-2-(4-benzyloxyphenyl)ethylesterNMR4-21.3-(4-methoxyphenyl)acrylicacid-2-(4-benzyloxy-phenyl)ethylesterNMRXII4-22.3-(4-methoxyphenyl)acrylicacid-2-(4-hydroxyphenyl)ethylester(6l)NMR4-23.3-(4-methoxyphenyl)acrylicacid-2-(4-hydroxyphenyl)ethylester(6l)NMRXIII(Abbreviation)BBBblood-brainbarrierCAPEcaffeicacidphenethylesterCATcatalasecPKCconventionalproteinkinaseCDAGdiacylglycerolDCCdicyclohexylcarbodiimideDiazogenN-methyl-N-nitrotoulene-p-sulphnamideDMAPN,N-dimethylaminopyridineDMSOdimethylsulphoxideDPPH1,1-diphenyl--picrylhydrazylEDTAethylenediaminetetraaceticacidERendoplasmicreticulumfMLPN-formyl-methionyl-leucyl-phenylalanineGRglutathionereductaseGSHglutathioneGSPHglutathioneperoxidaseHBSSHank’sbalancesaltssolutionH2O2hydrogenperoxideXIVIC5050inhibitionconcentrationIFN-γinterferon-gammaiNOSinduciblenitricoxidesynthaseIP3inositol1,4,5-trisphosphateLDLlow-densitylipoproteinLucigeninbis-N-methylacridiniumLPSlipopolysaccharideMTT3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromideNADPHnicotinamideadeninedinucleotidephosphateNF-Bnuclearfactor-kappaBNHOFnormalhumanoralfibroblastNOnitricoxideO2-superoxideanionOH-hydroxyanionOEC-M1oralepidermoidcarcinoma-Meng1PAFplateletactivatingfactorPBSphosphatebuffersolutionPIpropidiumiodideXVPIP2phosphatidylinosititol4,5-bisphospholipaseCPKCproteinkinaseCPMAphorobol12-myristate13-acetatePMNpolymorphonuclearleukocytesPSphospathylserineROSreactiveoxygenspeciesROO-peroxyradicalSASoralsquamouscellcarcinomaSODsuperoxidedismutaseTHFtetrahydrofuranTLCthinlayerchromatog