中德双边会议-潘远江.ppt

YuanjiangPanZhejiangUniversity2014 11 20 StilbenesfromParthenocissuslaetevirens Isolation BioactivityandImplicationofChemicalDefenseSysteminPlant PNAS 1999 96 13620 diterpene antifeedantactivityforbeetle PNAS 2000 97 14406 MalesofthemothacquirebyfeedingontheexcrescentfluidsofcertainplantsTheyincorporatethealkaloidsystemicallyandasaresultareprotectedagainstspiders pyrrolizidinealkaloid ChemicalDefenseinFlower IntheflowerofHypericumcalycinum dearomatizedisoprenylatedphloroglucinols DIPs areresponsiblefortheUVdemarcations DIPsfulfillbothavisualandadefensivefunction DIPsalsoserveforprotectionoffemalereproductivestructuresinotherplants GronquestM et al Proc Natl Acad Sci U S A 2001 98 13745 ChemicalDefenseinCatepillar Pinoresinol alignanofwidedistributioninplants isfoundtooccurasaminorcomponentinthedefensivesecretionproducedbyglandularhairsofcaterpillarsofthecabbagebutterfly Pierisrapae SchroederF C et al Proc Natl Acad Sci U S A 2006 103 15497 ROS reactiveoxygenspecies ROSincludebothradicalsandnon radicals Theyaregenerallyverysmallmoleculesandarehighlyreactiveduetothepresenceofunpairedvalenceshellelectrons ROSsformasnaturalbyproductsofnormalmetabolismofoxygenandplayimportantrolesincellsignaling CircuM L et al FreeRadic Biol Med 2010 48 749 762 EndogenousSourcesofROS ExogenousSourcesofROS RadiationUVlight x rays raysChemicalsthatreacttoformperoxidesozone singletoxygenChemicalsthatpromotesuperoxideformationquinones nitroaromatics bipyrimidiuliumherbicidesChemicalsthataremetabolizedtoradicalspolyhalogenatedalkanes aminophenolsChemicalsthatreleaseironferritin ROS ProteinDamage ChangC J et al Nat Chem Biol 2011 7 504 511 Aone electronreductionofmolecularoxygen eitherfromtheelectrontransportchain ETC orthroughtheactionofNADPHoxidases NOX yieldssuperoxide O2 Superoxideisconvertedtohydrogenperoxide H2O2 bysuperoxidedismutase SOD orbydismutationinaqueoussolution ROS CellDamage FinkelT HolbrookN J Nature2000 408 239 246 ROSdamages relateddiseases RelatedDiseasesInflammationAtherosclerosisCancerAging ROSdamagesActivationofcellularpathwaysStimulationofcellproliferationDamagetoproteins DNAandlipids Antioxidant anantioxidantisamoleculecapableofslowingorpreventingtheoxidationofothermolecules NaturalAntioxidants flavonoids黄酮类化合物 tannins单宁类化合物 stilbenoids茋类化合物 QuideauS et al Angew Chem Int Ed 2011 50 586 化妆品 SOD蜜Maquillage 海藻类Laminariajaponica 人参Ginseng 茶Tea 水果Fruits NaturalStilbenesasantioxidants FrechParadox Cardioprotection 法国异常 与保护心血管活性 Antitumor抗肿瘤活性 Antioxidant Anti aging抗氧化与抗衰老作用 TypeIIdiabetes抗II型糖尿病 Someplantphenolsmayactivatethegeneforlengtheningthelife GuaranteetalNature 430 686 2004 Inhibitionoflipidperoxidation TheproductionofMDAisanindexoftheoccurrenceoflipidperoxidationandthedevelopmentofoxidativestress Resveratrolpreventssuperoxide dependentinflammatoryinducedbyischemia reperfusion FreeRadicalBiology Medicine 5 6 2003 Vol 34 810 817 AntioxidantEffectsofResveratrolanditsAnaloguesagainsttheFree Radical InducedPeroxidationofLinoleicAcidinMicelles Chem Eur J 4 5 2002 8 No 18 4191 4198 StilbenesfromParthenocissuslaetevirens Isolation BioactivityandImplicationofChemicalDefenseSysteminPlant Family Vitaceae葡萄科Genus Parthenocissus爬山虎属Species ParthenocissuslaetevirensRehd Englishname ShinygreenCreeperChinesename 绿爬山虎 JapaneseCreeper Ref 1 AresveratroldimerfromParthenocissustricuspidataPhytochemistry1991 30 3144 3146 AstilbenedimerAresveratroldimer Resveratrol白藜芦醇 Stilbene Ref 2 AresveratroldimerfromParthenocissustricuspidataPhytochemistry1998 48 1241 1243 Resveratrol Antifungal Ref 3 StilbenederivativesinthestemofParthenocissusquinquefoliaPhytochemistry1998 48 1045 1049 Ref 4 Twonewantioxidantstilbenedimers parthenostilbeninsAandBfromParthenocissustricuspidataPlantaMedica2005 71 973 976 IsolationofresveratrololigomersfromParthenocissuslaetevirens Structureelucidationof5Molecularformula NegativeHR ESIMS m z 451 1178 M H Calcd forC28H19O6 451 1187 ResveratrolC14H12O3MW 228 Molecularformula C28H20O6 MW 452 Structureelucidationof513CNMRspectrum Structureelucidationof51HNMRspectrum Structureelucidationof51HNMRspectrum H 6 0 8 0 Structureelucidationof52DNMRData DeductionofStructureUnitA Structureelucidationof52DNMRData DeductionofStructureUnitB Structureelucidationof52DNMRData LinkagebetweenStructuresUnitAandB Structureelucidationof5NOESY Relativeconfiguration UVinducedcyclization Ref J Org Chem 2004 69 4279 4282 UVinducedtrans cisisomerizationandcyclizationof4 Structureelucidationof6NOESY Relativeconfiguration Methylationof7andOzonolysisof7a Absoluteconfiguration StructuresofgnetinF 13 and ampelopsinD 14 UVinducedtrans cisisomerizationandcyclizationof7 HPLCchromatogramofreactionmixtureat100min 7 680 6 680 8 678 Proposedschemefortheunknowncompound Oligomerization DimertoTrimer Idea HOW Ref 8 MonomertoDimer Chem Comm 1977 7 208 210 Ref 9 DimertoTetramer Tetrahedron1996 52 9991 9998 DimertoTrimer Experimental Firstexamplefromresveratroldimertotrimer Hybridreaction Yield28 Yield28 Resveratrol DimertoTrimer Experimental Resveratrol Yield26 Yield26 AntioxidantActivity DPPH 2 2 diphenyl 1 picrylhydrazyl astablefreeradical hasbeenextensivelyusedtoevaluatefreeradicalscavengingcapacitiesofcompounds Microplatereaderwasusedtomonitorthedecreaseofabsorptionat517nm With96 wellplate antioxidantactivitiesof32samplescanbedeterminedin1hourintriplicate HighThroughput Antioxidantactivitiesofresveratroldimers SC50 26 28 g ml SC50 30 38 g ml SC50 7 36 g ml Hypothesis Iscyclizationanantioxidantactivitypromotingreaction SC50istheconcentrationofsampleproducing50 decreaseofDPPHabsorption Thelowervalue thestrongerantioxidantactivity Whycyclizedproductsweresynthesized UV Antioxidantactivitiesofresveratroltrimers SC50 118 10 g ml SC50 87 04 g ml SC50 25 28 g ml Furtherevidenceforthehypothesis Cyclizationisanantioxidantactivitypromotingreaction UV Generationofactiveoxygenspeciesinthechloroplast 叶绿体 andantioxidativemechanisms Ref 10 Photooxidativestressinplants PhysiologiaPlantarum1994 92 696 717 Proposalofanewmechanismofantioxidativedefensesysteminplant WhentheplantwasexposedtoexcessiveUVirradiation reactiveoxygenspecies ROS wasgeneratedmassively whichwasdestructivetoplanttissues Inresponsetothisoxidativestress antioxidativedefensesystemwasactivated andcompoundswithstrongerantioxidantactivitiesweresynthesizedtoremoveexcessiveROS WehypothesizethatgenerationofcyclizedcompoundsisarespondencetoROSinducedbyUVirradiation thusstilbenesweresupposedtoplayaroleintheantioxidativedefensesystemofplant UVinducedtrans cisisomerizationandcyclizationofresveratrol HPLCchromatogramofreactionmixtureat8h trans resveratrol 228 cis resveratrol 228 Unknowncompound 226 2 trans resveratrol cis resveratrol UnknowncompoundProposedstructure UVirradiationonethylacetateextract 0min 120min Cyclizeddimer5 Cyclizedtrimer8 Biologicalimportanceofoligomerizationofstilbenes Whytrimerweresynthesized thoughtheirantioxidantactivitieswerelower SC50 26 28 g ml SC50 118 10 g ml SC50 172 1 g ml SC50 16 40 g ml Ref 11 AnewclassofphytoalexinsfromgrapevinesExperientia1977 15 151 152 ResveratrolNon antifungal Antifungal Antifungal Hypothesis Isperoxidasecatalysingoligomerizationanantifungalactivitypromotingreaction Antifungalactivitiesofstilbenes Non antifungal Antifungal Nottested InhibitionrateofgrowthofBotrytiscinerea 灰葡萄孢菌 at400 g ml Non antifungal Antifungalactivitiesofstilbenes Non antifungal Antifungal Nottested Non antifungal Antifungalactivitiesofstilbenes Non antifungal Non antifungal Antifungal Needmoreevidencetoprovethehypothesisthatoligomerizationpromotesantifungalactivity InhibitionrateofgrowthofBotrytiscinerea 灰葡萄孢菌 at400 g ml Molconcentrationofresveratrolwas3foldhigherthancompound8 Summary 10stilbeneoligomerswereisolatedfromtheEAextractofParthenocissuslaetevirens Fiveofthemarenewcompounds TheirstructurewereelucidatedbyNMRandMSdata Theirbiogeneticrelationshipwasprovedbyphotochemicaltransformationandenzymecatalysingoligomerization Theirantioxidantactivitieswereassayed TheresultsledtothehypothesisthatUVinducedcyclizationisanantioxidantactivitypromotingreactionandconsequentlystilbeneswereimpliedtoplayaroleintheantioxidativedefensesystemoftheplant Inaddition theresultsofantifungalactivitiesrevealthatenzymecatalysingoligomerizationmaybelinkedtotheantifungaldefensesystemoftheplant J Org Chem 2008 ResveratrolHexamerfromVitischunganeniss J Org Chem 2009 Proposedchunganenolbiogenesis 1 from3and5 DrivingForce Acknowledgements ThenationalnaturalsciencefoundationofChinaNCET 06 0520Allmystudents WelcometoZhejianguniversity Thanksforyourattention