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首页 Constituents of genus petasites—IV - Bakkenolid…

Constituents of genus petasites—IV - Bakkenolide-A, a sesquiterpene of novel carbon skeleton.pdf

Constituents of genus petasites…

上传者: silly 2010-05-24 评分 0 0 0 0 0 0 暂无简介 简介 举报

简介:本文档为《Constituents of genus petasites—IV - Bakkenolide-A, a sesquiterpene of novel carbon skeletonpdf》,可适用于工程科技领域,主题内容包含ktnkdmnVolpptoPqamonPIOPPrintedinGlmtnmainCONSTITUENTSOFGENUSPETASITESIV’B符等。

ktnkdmnVolpptoPqamonPIOPPrintedinGlmtnmainCONSTITUENTSOFGENUSPETASITESIV’BAKKENOLIDEA,ASESQUITERPENEOFNOVELCARBONSKELETONKSHIRAHATA,TKAY>andYKITAHARA*DepartmentofChemistry,TohokuUniversity,No,Katahiracho,Sendai,JapanandNABEFacultyofEducation,AkitaUniversity,Akita,Japan(ReceivedinJapanJanuaryReceivedintheCJKforpublicationFebruary)AhactAgroupofanewtypeofsesquiterpene,namedbakkenolideA,B,C,D,andEwasisolatedfromthebudsofPermiresjuponicus(SiebetZucc)Maximsubspgiganteus(FrSm)Kitam(Japanesename,Akitabuki)TheyhaveanovelspiroylactonegroupingThestructureandstereochemistryincludingabsoluteconfigurationwasestablishedforbakkenolideA(BA)()onthebasisofchemicaldegradations(ChartI,)andphysicalmeasurementsTheC,,dicarboxylicacid()amaindegradationproductofBAduringpotassiumpermanganateoxidation,wasinstrumentalindeterminationofthefullstructureTheabsoluteconfigurationwasbasedonthetransformationofBAtotheknownperhydroindanonederivative()THEantitussiveandpepticpropertiesofbudsofthegenusPetasiteshavebeenknowninJapanandgroupshavereportedtheisolationofsesquiterpeneswiththeeremophilaneskeletonfromPetusitesjuponicusNovotnyetcdalsohavereportedmanystudiesonthecomponentsofEuropeanPetasitesWewereinterestedinthemedicinalpropertiesandthebitterprincipleofPetasitesjuponicus(SiebetZucc)Maximsubspgiganteus(FrSchm)Kitam,thedistributionofwhichislimitedtothenorthernpartofJapanDuringtheinvestigationofthecomponentsofthebuds,weisolatednewsesquiterpenelactoneswhichwerenamedbakkenolideA,B,C,D,andEafterthelocalname“Bakke”forthebudofthisplantThepresentpaperdiscussesthecompletestructureincludingthestereochemistryofBakkenolideAtBakkenolideA(l),mp”,CHZZ(M,molwt*),hasIRabsorptionat,,andcm’andhasonlyweakendabsorptionintheUVspectrumThespectraldataindicatedthepresenceofanunconjugatedterminalmethylenegroupandaylactonegroupingThisdeductionwasverifiedbyanobservationwhichledtothepartialstructurelaBAisinsolubleincoldbutsolubleinhotaqueousalkalitoformasodiumsaltwhichregeneratesBAonacidificationF“,”“”c,cWHuCCy)CyIIHHO’HiH”HC,HlbIClTowhomallcorrespondenceshouldbeaddressedtApartofthisworkhasbeenpublishedinpartIofthisseriesasashortcommunication,seeRefIKSHIRAHATA,TKATQYKITAURAandNABEFIGMCNMRspectrumofbakkenolideA()indeutcriobenzeneTheNMRspectrumofRAindeuteriobenzene(Fig)showsthesignalsoffourprotonsatppmGHr,,*tandH,,,=,H,,,andH,,,,=and,J(ab)=,J(aa)=J(Kkb)=J(ba)=J(bb))=ca,J(ab)=ca,whichindicatedthepartialstructurelborlcRAconsumedonemoleequivalentofhydrogenoncatalyticreductionwithPdCinethanoltoaffordamixtureofstereoisomericdihydroderivatives()C,,H,O,TheIRspectrumofthemixtureindicatedastrongylactonebandatcm‘TheNMRspectrumofthepredominantisomerindeuteriochloroform(Fig)showstwosecondaryMegroupsatppm(doublet,J=O)andppm(doublet,J=O),(aorb)groupingH,,,andHIZbatandppm,J(ab)=,J(a)=,(b)=,andamultiplet(Hi,)atppmThelattersignalbecameaclear:::quartetwhenbothHaandHbwereirradiatedatthesametime(Fig)ThistripleresonanceexperimentindicatedabsenceofaprotononthecarbonnexttoCirStrongirradiationofHi,atresultedindecouplingsofthenewsecondaryMedoubletatppmtosinglet(Fig)aswellasbothHi,andHIZbtoapairofdoubletsTheseobservationsindicatedthatthedihydroderivativehasthepartialstructurea,andnoth,particularlyinviewofthechemicalshiftsofHaandHi*,,CH,CH,ab*Inthecaseofasignalduetotwoprotonsonthesamecarbonifthecorrectassignmentcouldnotbegiven,thenthesuffiuesaandbwereusedThesesuffixes,therefore,havenotanystructuralmeaningtThenumberingwasgivenafterconsiderationofthebiosynthesisofthecarbonskeletonwhichmaybederivedfromtheeremophilaneskeletonintbeplantSeepartIIIofthisseries#ThesymbolnrefersacarbonbearingnohydrogenConstituentsofgenusPetapitesIVLIAppFIGMCNMRspectrumofamixtureofdihydrobakkenolidcA()stereoisomersatC,indeuteriocbloroformThenatureofthelactonegroupingwasmadeevidentbyreductionofEAwithLAHTheproductwasacrystallinediol()CiSH,,O,,mp”(IRbandatcm‘,formationofadiacetate)TheNMRspectrum(Fig)ofindeuteriochloroformexhibitsadiffusesingletat(twoOH),anARtypequartetcenteredatThenewquartetcouldbeassignedtothetwohydrogensoftheCsmethyleneI’hissplitting(Jab=)wasduetogeminalcouplingandhenceshowedthatC,hasnoprotonThespectraldataalsoconfirmedthepartialstructureaforandlaforEAThusitwasconcludedthatBAisaSpiroylactone*(Cring)havingaterminal:oI~oL~PpmFIGMCNMRspectrumofAdiol()indeuteriochloroformlTheSpiroylactonesuchasBAisnotcommoninasesquiterpenetoneThisisthefirstexampleasfarasweknowKNayaetalhavealsoreportedthatbakkenoldeA,BandDwereisolatedfromPetusitesjaponiafsMaxim*tTheandSmemberedringsinturnsaredbedasAandBringSetstructureKSHIRAHATA,TKATO,YKITAHARAandNABEmethyleneontheringInconjunctionwiththemolecularformula,thepresenceofonlyonedoublebondandalactonedeterminesthatBAistricyclicThestructureoftheremainder(B,Cring)ofBAwasdeterminedasfollowsOxidationofBAorthediowithpotassiumpermanganateinaqueousalkalinesolutionaffordedamixtureofseveraldegradationproducts,themainproductofwhichwasCiidicarboxylicacid()CiH,sO,Thisdicarboxylicacidreadilygaveanacidanhydride()whenheatedinaceticanhydride,theIRspectrumofwhichshowedbandsatandcm’characteristicofananhydrideofasixorlargermemberedringThenatureofthecarboxylgroupswasdeducedfromobservationoftherateofesterexchange(conversionof<OH,toCOD,)ofthedimethylester()whichwasobtainedbytreatmentofthedicarboxylicacidwithdiazomethaneThedimethylesterwasdissolvedinmethanold,containingsodiummethoxided,(cawtofsodiuminmethanold,)andtherateindecreaseoftheMesignalswascheckedbyNMRAlthoughthetwoesterMesignalshavethesamechemicalshift,thesignalarea(H,relativetotertiaryMe,H)wasreducedtohalf(H)atroomtemperaturebutwasnotreducedtolessthanhalfafterstandingforhratroomtemperatureandforanotherhrat”ThisexperimentdemonstratedthatonlyoneofthetwocarbomethoxygroupsinistertiaryConsiderationofthepresenceofatertiaryMegroupanditschemicalshift(lppm)ledtothepartialstructureatothedicarboxylicacid(anothercarboxylgroupshouldnotbondtoClorC,)FIGMCNMRspectrumofC,,dicarboxylicacidindeuteriobenzeneTheNMRspectrumofindeuteriobenzene(Fig)shows,inadditiontoatertiaryMegroup(singletatl)andasecondaryMegroup(doubletat,J=),agroupofsignalswhichischaracteristicofanABCpatternwheretheCproton(ppm)isfurthercoupledtotwoadditionalprotonscfFig,andstructure!IhH,,(A)andHB)atandppm,H(C)atppmJ(ab)=,CttstitucntsofgenusPetasitesIVJ(a)=,J(b)=,J(lOla)=J(lOlb)=caThesesignalsclearlyindicatedthepresenceofthesequenceCHCH,COOHThechemicalshiftsofHgandHio,themagnitudeofJ(ab),thepresenceofthepartialstructureSa,C”,IHOOCCICakSaSbthefacilitywithwhichthetwocarboxylgroupsformedananhydrideandtheanhydrideringlargerthanamemberedring,aswellascouplingofHItoonlytwoprotonsexceptH,,andH,,,allconfirmedthepresenceofpartialstructurebMoreover,consideringthepresenceofonlyoneadditionalsecondaryMegroupandtheabsenceofanyolehnicprotons,theC,,dicarboxylicacid()mustbeasaturatedcyclohexanederivativeThepositionofthesecondaryMegroup,andhencefullstructureofwasbasedonthefollowingmultipleresonance(i)IrradiationofthesecondaryMegroupatcausedthebroadmultipletsignal(HJunderlyingtheH,,signaltoshowasadoubletofdoubletcenteredatppm,whereas(ii)irradiationnearppm(H,,andHJchangedthisHsignaltoabroadquartetagaincenteredatnearppm,and(iii)simultaneousirradiationatbothandppmconvertedthesignalattoabroadsinglet*Thesedecouplingexperiments,BAlLAHROPROR=HR=AClThebroadnessofthequartetandsingletinthelasttwocaseswasattributedtoincompletedecouplingoftheapparentlybroadmultipletsatnearppmduetotheC,protonsKSH~MA~A,TKATO,YKITAHARAandNABEparticularlythoseof(i),arebestexplainedintermsofaI)CH(CHCH,groupingwhichimmediatelyledtoproposalofstructureforthecarboxylicacidandoffortheanhydride,andhenceAringofBAwaspresentedasldcIdTheNhRspectrumofRAshowsfoursharppeaksat,*,*andppmThefollowingspinticklingexperimentsindicatedthatthesefourpeaksconsistofanARtypequartetisolatedfromotherspinsystemsWeakirradiationofoneofthematppm(Fig(iJ)madethepeakatppmdecreaseinheightandsplittoadoubletandmadethepeakatppmincreaseinheightbutnotchangethesplittingSimilarirradiationofthepeakatppm(Fig)madetheformer(l)increaseinheightandsplittoadoubletandmadethelatter()decreaseinheightandsplittoadoubletTherefore,BAhasHzgroupinginRringAll*ppnFIQSpinticklingofBakkcnolideAderivativesofBAretainingBringalsoshowtheARtypequartet(Table)Thereisonlyonepossiblecombinationofpartstructuresla,IdandIllcH,groupingandthefullstructureofBAisthereforeThestereochemistrywasestablishedasfollowsTheNMRspectrumofBAshows$ignalsatppmduetothreeprotonsKSHIRAW~A,TKATO,YKITAHARAandNABE:OHmel:X=CH,:x=<“,,TherelativeconfigurationatC,wasbasedonaconsiderationofanisotropyeffectsoflactonecarbonylandexocyclicmethylenedoublebondtotertiaryMegroup(Table)ThechemicalshiftoftheMegroupindeuteriochloroformsolutionwaslittleatedwhenthedoublebondwassaturatedoroxidizedtocarbonylOntheotherhandthecharacteristicupfielddisplacement(Oppm)wasobservedwhenTABLETHECHEMICALsmsOFC,MeINCDCI,BA()DihydroA()Norketone()BAdiol()thelactonecarbonylwasremovedbyreductiontodialThesefindingssuggestedthattheCOgroupandthetertiaryMegroupareonthesamesideofthemoleculeinBAAbsolutecon~~mtionandstereochemistryatallcentersexceptingC,wereestablishedbyconversionofBAtotheperhydroindanonederivative()ofknownstructureandstereochemistryThetreatmentofEAwithosmiumtetroxideandsodiumperiodateindioxanaffordedadegradationproduct,norxbakkenolideA(norketone)(),CiHZ,whoseIRspectrumshowsthattheexocyclicmethylenewasconvertedtoketone(disappearanceofIRbandsat,andcm’originallypresentinBA)andtheNMRspectrumshowstheCizmethyleneprotonsatppmasasingletThisnorketonewasoxidizedwithsodiumhypobromidetoCljdicarboxylicacid(),whichwasidentifiedafteritwasconvertedtoitsdimethylester(lo),Hz,whichhasstrongabsorptionatcm‘InspectionofitsNMRspectrumprovidedclearproofthatthedimethylesterretainstheBring,ieapairofdoubletscharacteristicofC,methyleneprotonswasshownatandppm(J=cs)(Table)Treatmentofwithleadtetraacetateandpyridine’followedbyhydrolysisoftheresultingdiacetate()withmethanolicINaOBrHOOCdimethylesterpb(OAc)HOOCPyridiIlCOHm,dinitrophenylhydroIHIpotassiumhydroxidegaveaketone()asacolorlessliquid,whoseIRspectrumshowsastrongmemberedCObandatcmIThedinitrophenylhydrazoneofwasidenticalwiththatobtainedfromfukinone()’bycomparisonoftheirIRspectrumandrapsThefullstructureofBAincludingabsoluteconfigurationwaseventuallyestablishedasEXPERIMENTALMpsweretakenwithaThomasHooverCapillaryMeltingPointApparatusandareuncorrectedTheIRspectraweremeasuredwithHitachiEPISmodelequippedwithrocksaltprisms,whilemeasurementofsolutionwascarriedoutbyaHitachiEPIGZgratingspectrometerTheNMRspectraweremeasuredwithaVarianA(MC)andaVarianHA(MC)spectrometersequippedwithspindecouplersThechemicalshiftsareexpressedinppmusingTMasaninternalreferenceThemassspectrawererecordedwithaHitachiModelRMUDspectrometerIsolationojbakkenolidesFreshbuds(Kg)oftheplantwerecrushedandsoakedinhotMeOH,andthesoln(L)containinglargeamountofwaterwasconcentratedandextractedwithbenzeneThebenzenesolnwasconcentratedinuucuotofordadarkgreenishviscousliquid(g),whichwassubmittedtosteamdistillationBakkenolidbA(g)wasobtainedimmediatelyfromthedistillateasleafletsABcrBAwasfilteredoff,thefiltratewasextractedwithetherandtheextractswereprocessedintheusualmannertoaffordaneutralliquid(g),whichwasdistilledandthefraction(lOOlWmmHg)waschromatographedoversilicageltogiveanothercropofBA(g)Theresidueaftersteamdistillationwastakenupagainwithbenzene,thebenzenesolublepart(g)waschromatographedoveraluminawithpetether,benzene,benzeneether,andMeOHascluentsBakkenolideB(g),D(g)andC(g)wereobtainedinturnfromthebenzene,benzencether,andMeOHeluentsrespectivelyAfterBBandBCwereisolatedbyfiltration,thecombinedresidueswereagainchromatographedoversilicagelElutionwithbenzeneethergavebakkenolideE(Og)BakkenolidbAC,sH,,O,leafletsfromnpentanc,=BC,,H,oO,needlesfromEtOHCC,oH,sOsneedlesfromether”DC,,H,sO,needlesfromMeOH~’ECstH,oOneedlesfromMeDH”lInsomecasesdifferentmps,ie”and”,wererecorded,whichcouldbeduetopolymorphismConstituentsofgenusPetaS~IVlayawasqarated,thecombinedaqueouslayerwasextractedwithethertoremoveneutralmaterialsTheresultingaqueouslayerwasacidifiedtopHcawithNHClandthenextractedwithethertimes(mlandmlx)TMextractswerewashedwithwater,driedoverMgSO,andevaporatedtogiveawhitesolid(mg),whichwasdividedintoanpentanesolublepartandinsolublepart(mg)TheformergavetheC,,dicarboxylicacid(mg),whichwasrecrystalhzdfromwatertoaffordcolorlessneedles,mp”TriturationofapartofthelattawithcyclohexanetoobtaincrystalsresultedindecompositionandgaseousevolutionTreatmentofanotherpartofthiswithetherealdiaxomethanegaveacolorlessliquidwhichwasidentifiedasCkarboxylicaciddimethylestcr()byVPCAcidanhydride()Inasealedtubeasolnof(ms)inAc,O(ml)washeatedat”forhrAfterthesolventwasevaporated,theresultingcolorlessliquidwaskeptvucaountilthecdourofAc,OdisappearedThecrudeacidanhydride(mg)containedcaofstartingmaterial(NMRevidence)v,(liquid),and(anhydride),,andcm‘NMRdata(CCcontainingcabenzeneMCS):ad(J=)at(CdMe),asat(Me),adofd(J=and)at(HI,H,,),adofd(J=and)at(lH,HP),andmatnear(CH)andnearl(C,,H)Dimethylester()ofC,,dicurboxylicacidAsolnofcrudeS(mg)inetherwastreatedwithetherealdiaxomcthaneundericecoolingThesolnwaswashedsuccessivelywithNa,CO,aqandwater,andthendriedEvaporationofthesolventgaveasacolourkasliquid(mg)Aportion(ma)ofthiswaschromatographedongsilicagelinbenxenecyclohcxane(:)Fractionscontainingthedesiredproductwerepooledandconcentratedgivingmgof,whichwasdistilledatmmHgand”(bathtemp)(Found:~~~~C,,H,,O,rtquircs:C,~~~~~M’wasmcasurcdatme~(C,,H,,O,requires)v,(liquid),(ester),,,andcmiEsterexchange(COOCH,toCOOCD,)Thedimethylester(mg)wasdissolvedinMeOHd,(ml)andtheNMRspectrumwasmeasuredTothissohrintheNMRtubewasaddedasolnofMcONad,inMeOHdCpreparedbyadditionofNa(mg)toMeOHd,(ml)atroomtemp(”)ThefirstrunoftheNMRmeasurementstartedafterminInspectionofthespectrumindicatedwhentheexchangewascompleteAfterstandingforhratroomtempandthesolventwasdistilledoffunderN,at”(bathtemp),newMeOHd,(aboutBlml)wasaddedAfterthisoperationwasrepeatedthriceandfollowedbystandingforhrat”,theNMRwasmeasuredThespectrumofthisrunrevealedthatnoperceptibkchangeintheratioofCOOCH,toCOOCD,hadoccmredandanyexchangeoftheactivemethyleneprotonstodeuteriumsatapositionofthecarbomethoxygroupwasnotobserved(H,ppm)buttheshapeofthespectruminthisregionwasaffectedNoro~bfcenolideA()Toasolnof(mg)inamixtureofdioxan(ml),water(ml)andAcOH(ml)wasaddedmlosmiumtetroxidesolnpreparedfromosmiumtetroxide(mg,mmol),dioxan(ml)andwater(ml)andsodiumperiodide(g)duringminARerthemixturewasstirredatroomtempforhr,itwasdilutedwithwaterTheetherealextractofthemixturewaswashedsuccessivelywithNa,CO,aqandwaterandthendriedandconcentratedThecrudeproduct(mg)wasrecrystallizedtwiafromnpentanetogiveapuresampk(mg,prisms),mp”(Found:CH,C,,H,,Oarequires:C,)Mwasmeasuredatme(C,,H,,O,requires)v,(KBr),,and(ylactoneandketone),,andcmiNMRdata(CDCl,MCS):ad(J=)at(C,Me),asatW(Me),apairofd(J=)atl(H,,Jand(H,andasat(H,H,andH,,s)Thiscompoundsublimatedat”(bathtemp)undermmHgDuringanotherrun

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