Spectroscopy-1-introduction

NaishengBai，Ph.D白乃生,博士应用光谱解析Spectroscopy教育经历学士(BS),1980.9－1984.7延安大学化学系化学硕士(MS),1989.9－1992.7中国科学院上海药物研究所药学博士(Ph.D),1999.8—2003.5美国Rutgers,theStateUniversityofNewJersey天然产物化学主要工作经历1984.7-1989.8延安大学化学系助教1992.7-1997.5河北科技大学有机化学教研室讲师1997.5-1999.8河北科技大学有机化学教研室副教授1997.8-1999.1美国Pharmanex,Inc.上海研究中心高级研究员2002.11-2011.5美国Naturex/PureworldInc.研究中心高级研究员OutlineofPresentationNaturalproductsdrugdiscoveryPlantmaterialselection(Bioassay)ExtractionandisolationStructureelucidationBioactivityevaluationAdvantagesofdrugdiscoveryfromnaturalproducts(uniqueanddiversestructures)NaturalproductsresearchinIndustryFutureResearchPlantMaterialSelection,ExtractionandIsolationofCompoundsTraditionalvaluableUniquestructureandpromisingactivityreportedExtractedusingpropersolvents/partitionFractionationusingtraditionalmethodsPurificationbymodernchromatographytechniquesStructureElucidationDeterminationofChemicalStructures1HNMR,13CNMR,DEPT1H-1Hcorrelation2Dspectra(COSY,TOCSY,ROESY),1H-13Cheteronuclearcorrelation(HMQC,HMBC)MS,HRMS,X-ray,andchemicaldataHHOOOOHCHCO31-O-acetylbritannilactoneX-rayExample-5:Anti-diabeticActivityofFraxinusexcelsiorL.Thebarkandtheleavesagainstdiseases,includingwoundhealing,diarrheaanddysentery,againstfeverandrheumatism.F.excelsioraqueousseedextracts(FE)tobehighlypotentinthereductionofbloodglucoselevelswithoutsignificantlyaffectinginsulinlevels.Chemicalcomposition:secoiridoidglucosides,coumarins,flavonoids,phenylethanoids,benzoquinones,indolederivatives,andsimplephenoliccompounds.OCOOCH3OCH3OOOHHOHOOOOOHOHHOHOOCOOCH3OOOOHHOHOOOHROCOOCH3OOOOHHOHOOOOOHOHHOHOHO7R=H8R=MeOCOOCH3OOOOHHOHOOOHHOOOHOHHOHOOOOOHHOHOOHOOCOOCH3OOCOOCH3OOOHHOHOOHOOOHOHOHOOHOOOCOOCH3OHOHOOHOCOOCH3OOOOHHOHOOOHOOHOOOHOHHOHOOHOOCOOCH3OOOOHHOHOOHOOOOHOHOHOOHOOOCOOCH3OOHHOHO123645109ActivecompoundsfromFraxinusexcelsiorL.NewexcelsideA(1)andB(2),Compounds1-9showedinhibitoryactivityagainstadipocytedifferentiationin3T3-L1cells(anti-obesity).Thewaterextract11,andthecompounds5,8,9,10,and4weremodestlyactivetoinhibitnitriteproductioninmacrophages(Anti-inflammatory),followedbycompounds3,2,1,6,and7.Therearenoeffectof1-11onthegrowthofvarioushumancancercells(meansnotoxicity).HPLCchromatogramoftheextractfromtheseedsofF.excelsiorAcalibrationcurvewasconstructedfornuzhenide(3),andGI3(4).BasedonHPLCanalysis,thecompoundscontentintheextract11orFE994702islistedas2,0.41%;3,11.42%;4,6.15%;5,0.63%;7,0.19%;9,1.35%;10,0.20%;andtotalcontentoftheidentifiedcompounds,20.35%.Figure.Compoundlabel:FE19028(Nuzhenide),FE20015(GI3),FE20031(oleosidedimethylester),FE21008(excelsideA),andFE21023(GI5).AqueousextractsF.excelsior(1:10,000)aswellas2,3,4,5,and8wereactivatinginperoxisomeproliferator-activatedreceptor-α(PPAR)reportercellsystemintherangeof10-4Mcomparableto10-8–10-7MWY14,643,aknownsyntheticpotentactivatorofPPAR.020406080100120140DMSOWY14,643-5MWY14,643-6MWY14,643-7MWY14,643-8MWY14,643-9MFE19028-4MFE20015-4MFE20031-4MFE21008-4MFE21023-4MFraxiPureEXTRACT1:10relativeactivation(%)PPARactivationpotentialinreportercelllinesFig.1.FraxiPure™limitsweightgainsandhyperglycemiainhigh-fatdiet-inducedobesemiceFraxiPure™reducedgainsinbodyweightby32.30%(p0.05),omentalfatby17.92%,andretroperitonealfatby17.78%.Fig.2.Fig.3.FraxiPure™limitsweightgainsandhyperglycemiainhigh-fatdiet-inducedobesemiceFraxiPure™alsoloweredfastingbloodglucoselevelsby76.52%(p0.001)andplasmainsulinlevelsby53.43%(p0.05)after16weeks.FraxiPure™loweredliverweightgainsby63.62%(p0.05)andtheincidenceoffattyliversby66.67%.I期临床研究Figure.ComparisonbetweenFraxinusexcelsiorLseedextract(FE)(1.0g)andmatchedwheatbranplacebo(1.0g)onglycemiainhealthyvolunteersadministratedwith50gofglucose.(A)Incrementalglycemiaatindividualtimepoints.(B)Areaunderthebloodglucosecurve(AUC).Valuesaremean±SEM.*P=0.02,pairedStudent’sttest(n=16).FraxiPure™reducedglycemiainhealthyvolunteers,followinganoralglucosetolerancetest.ThesefindingssuggestthatFraxiPure™hasantiobesityandantihyperglycemiaeffects.0123456306090120Time(min)PlaceboF.excelsior(A)0100200300400500PlaceboF.excelsior*(B)IncrementalGlycemia(mmol/L)AUC(min.mmol/L)00123456306090120Time(min)PlaceboF.excelsior(A)0100200300400500PlaceboF.excelsior*(B)IncrementalGlycemia(mmol/L)AUC(min.mmol/L)0Figure.ComparisonbetweenFraxinusexcelsiorLseedextract(1.0g)andmatchedwheatbranplacebo(1.0g)oninsulinlevelsinhealthyvolunteersadministratedwith50gofglucose.(A)Incrementalinsulinemiaatindividualtimepoints.(B)Insulinemicareaunderthecurve(AUC).Valuesaremean±SEM.**P=0.002,Student’sttest(n=16).03060901200306090120Time(min)PlaceboF.excelsior(A)**02,0004,0006,0008,000PlaceboF.excelsior(B)InsulinemicAUC(min.mU/L)IncrementalInsulinemia(mU/L)03060901200306090120Time(min)PlaceboF.excelsior(A)**02,0004,0006,0008,000PlaceboF.excelsior(B)InsulinemicAUC(min.mU/L)IncrementalInsulinemia(mU/L)I期临床研究(con.)SummaryforFraxinusexcelsiorL.Inconclusion,thisstudyconfirmsthecapacityofFraxinusexcelsiorL.tocontrolbodyweightandsupportstheexistingevidenceofitsantihyperglycemiaeffectsanditsabilitytoimproveresist