ganotheaecolin a, a neurotrophic conjugated ergosterol with a naphtho[1,8-ef]azulene scaffold from ganoderma theaecolum 2017 qi luo学术.pdf


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该【ganotheaecolin a, a neurotrophic conjugated ergosterol with a naphtho[1,8-ef]azulene scaffold from ganoderma theaecolum 2017 qi luo学术 】是由【探春文档】上传分享,文档一共【4】页,该文档可以免费在线阅读,需要了解更多关于【ganotheaecolin a, a neurotrophic conjugated ergosterol with a naphtho[1,8-ef]azulene scaffold from ganoderma theaecolum 2017 qi luo学术 】的内容,可以使用淘豆网的站内搜索功能,选择自己适合的文档,以下文字是截取该文章内的部分文字,如需要获得完整电子版,请下载此文档到您的设备,方便您编辑和打印。Letterpubs./OrgLettGanotheaecolinA,onjugatedErgosterolwithaNaphtho[1,8-ef]azuleneSca?oldfromGanodermatheaecolum??§??QiLuo,,Zhu-LiangYang,Yong-MingYan,andYong-XianCheng*,?§StateKeyLaboratoryofPhytochemistryandPlantResourcesinWestChina,KunmingInstituteofBotanyandKeyLaboratoryforPlantDiversityandBiogeographyofEastAsia,KunmingInstituteofBotany,ChineseAcademyofSciences,Kunming650201,?UniversityofChineseAcademyofSciences,Beijing100049,*SSupportingInformationABSTRACT:GanotheaecolinA(1),anovelergosterolwithararenaphtho[1,8-ef]azuleneringsystem,-fusedcarbonskeletalergosteroltypicallyformedbyWagner?Meerweinrearrangement,whoseplausiblebiosyntheticpathwaywasbrie?,(1),11obtainedasayellowgum,possessesmedicinesinChina,Japan,Korea,andotherAsiancountriesamolecularformulaC28H40O3deducedfromitsHRESIMS,,andDEPTspectra,,harides,meroterpenoids,The1HNMRspectrum(Table1)of1containssixmethylalkaloids,nucleotides,steroids,fattyacids,proteins/peptides,signalsincludingtwomethylsinglets,fourmethyldoublets,and?andtraceelements,14whichpossessvariouspharmacological?veole?,antitumor,antiin?am-carbonsascribedtosixmethyls,?vealiphaticmethylenes,1023matory,anti?brotic,antidiabetic,hepatoprotective,antibacterial,methines(?vespand?vesp),andsevenquaternarycarbons23antiviral,antioxidative,antiaging,andsleep-promotingproper-(oneketone,threespincludingoneoxygenated,andthreesp?).Thesespectraldatapromptedusto121?(Figure2)of1showsthepresenceofH-1/H--3,H-11/H-12,H-14/H-15/H-16/H-17/H-20/H-22/H-,investigationsonthisspecies23/H-24/H-25/H3-26,H-20/H3-21,H-24/H3-28,andH-25/--19/C-1,C-9(),fungi,ponentsofthetitle3CC-10,H-1/C-9,C-10(),H-2/C-4(),andH-3/species,resultingintheisolationofganotheaecolinA(1,C--OH1)withanunprecedentednaphtho[1,8-ef]azuleneringsystem,δδδδ()/C-4,C-5(),C-6(),andH-7(Hrepresentinganovel6/6/7/5-,s)/C-5,C-8(),andC-9suggestthatringsAandInspiredbythetraditionalmedicinalusesofGanodermafor?,wefound1tobeasmall-moleculesupportedbytheHMBCobservationsofH-11/C-9,C-10,C-,H-12/C-10,C-13,C-14,andH-14/C-7,C-8,C-9,C-,thepivotalmotif(ringsA?C)ofcompound1wereunambiguouslyclari?,HMBCcorrelationsofH3-18/C-12,C-14,C-17,H-16,H-17/C-,(23)doublebond,thelargecouplingconstantofH-22(J=)suggestsittobetheE-?:January3,2017?XXXXAmericanChemicalSocietyADOI:.,XXX,XXX?(600MHz)and13C(125MHz)NMRDataof1(δinppm,JinHz)(,)(,)(,)()(),theabsolutecon?gurationsatC-20andC--21andH--?eldshifted(,()()).13,14Therefore,1wasassignedasthe20RformduetoH-,-(forexample,,).15,16Inthepresentstudy,H-(,)(,)-con??(C22C28)of1withthoseof(24R)-ergosterol,17whichwascon?rmedbysingle-crystalX-?(TableS1,SupportingInformation).,24R-,17Incontrast,?weremainlychemicallysynthesized,15,??()(),(,)(,)?(,)(,),ECD()(9R,10S,13R,14R,17R,20R,24R)-1or(9S,10R,13S,14S,-()(),20R,24R)-()()(9R,10S,13R,14R,17R,20R,24R)-()()(Figure4),suggestingtheabsolute5----,10S,13R,14R,17R,20R,24Rand9S,10R,13S,14S,17S,20R,24RattheB3LYP/6-311G(d,p)levelwiththeexperimentalspectrumof1inMeOH,σ=,shift=+(Figure3).IntheROESYspectrum,thecorrelationsbetween9-OH(inDMSO-d6)/Ha-1,Ha-11,H3-19/Hb-1,Hb-?11,H3-18,H3-18/H-20,andH-14/Ha-11,H-17areobserved,congurationof1tobe9R,10S,13R,14R,17R,20R,-orientationfor9-OH,H-14,andH-17andtheConsideringthat1bearsanewcarbonbackbone,theβ13-formforCH3-18andCH3-,MRchemicalshiftsof(9R,10S,13R,14R,-con?gurationdeterminationofC-20andC-24inthe?exible17R,20R,24R)-1attheMPW1PW91/6-311+G(2d,p)-raydi?ractionisadirectthePCMinMeOHwere??gurationof1;however,thethatthecorrelationcoe?cient(R2)?edcrystalfor1oritsderivativeeventhoughwehave(Figure5),andthecorrectedmeanabsoluteerror(CMAE)istriedtopreparetheacetateof1(datanotshown).(TableS5,SupportingInformation),supportingtheBDOI:.,XXX,XXX?XXXOrganicLettersLettersurvival,migration,anddi?,theinabilityoflargeneurotrophicmoleculestocrosstheblood?brainbarrierandadversee?-moleculeneurotrophicfactormimeticsthaticandside-e?,,26,27compound1wasevaluatedforitsneuriteoutgrowth-(TableS6andFigure6)with5ng/mLNMRchemicalshiftsof(9R,10S,13R,14R,17R,20R,24R)-1attheMPW1PW91-SCRF/6-311+G(2d,p)level;linear?,theDFT-,,thereshouldexistaketo?,the1HNMRof1indicatesthatonlytheenoltautomerispresent,,-pound1in?rstexampleofa6/6/7/5-fusedcarbonskeletonsteroid,±,***p<?Meerweinrearrangementof(22E,24R)-5α-hydroxyergosta-2,7,22-trien-6-one(1a)21(Scheme1).First,thekeyintermediateAisgeneratedfromand50ng/mLofNGFasthenegativeandpositivecontrols,?erentiationinadose-dependentmannerandreachamaximume?ectat10μM,indicatingitspotentialinneurotrophicfactormimetics.■ASSOCIATEDCONTENT*SSupportingInformationatTheSupportingInformationisavailablefreeofchargeontheACSPublicationswebsiteatDOI:.1D,2DNMR,putationalmethods,detailedisolationprocedures,andbioassaymethods(PDF)■*Phone/fax:+86-871--mail:******@(9→10)-.skeletonbyWagner?MeerweinrearrangementofmonomerORCID12,,ouldbecyclizedviaYong-XianCheng:0000-0002-1343-0806nucleophilicreactiontogenerateD,whichcouldbetrans-formedtoEbyfurtherketo?,1wasNotesestablishedbystereospeci??’sdiseaseandParkinson’sdiseaseareconditionswherecellsofthebrainor■ACKNOWLEDGMENTSspinalcorddegenerateanddie,markedlya??ectivetreatmentsforthesediseasesDistinguishedYoungScholars(81525026),theNSFC-(U1202222),andtheNationalexempli?edasnervegrowthfactor(NGF)andothermembersNaturalScienceFoundationofChina(21472199).,Chinesetheirtherapeuticpotentialsinregulatingtheproliferation,AcademyofSciences,:.,XXX,XXX?XXXOrganicLettersLetter■REFERENCES(1)Wang,K.;Bao,L.;Xiong,.;Ma,K.;Han,.;Wang,.;Yin,.;Liu,,78,1977?1989.(2)Ferreira,.;Heleno,.;Reis,.;Stojkovic,.;Queiroz,.;Vasconcelos,.;Sokovic,,114,38?55.(3)Yan,.;Ai,J.;Zhou,.;Chung,.;Li,R.;Nie,J.;Fang,P.;Wang,.;Luo,J.;Hu,Q.;Hou,.;Cheng,Y..,15,5488?5491.(4)Liu,.;Wang,.;Peng,.;Qiu,,1,93?96.(5)Yan,.;Wang,.;Zhou,.;Zhou,.;Li,R.;Tian,Y.;Zuo,.;Fang,P.;Chung,.;Hou,.;Cheng,,176,385?393.(6)Luo,Q.;Di,L.;Dai,.;Lu,Q.;Yan,.;Yang,.;Li,.;Cheng,Y..,17,1110?1113.(7)Luo,Q.;Di,L.;Yang,.;Cheng,,6,45963?45967.(8)Luo,Q.;Tian,L.;Di,L.;Yan,.;Wei,.;Wang,.;Cheng,Y..,17,1565?1568.(9)Luo,Q.;Wang,.;Di,L.;Yan,.;Lu,Q.;Yang,.;Hu,.;Cheng,,71,840?845.(10)Liu,.;Kang,J.;Wu,.;Li,Y.;Chen,,41,1075?(11)GanotheaecolinA(1):yellowgum;[]D+(,MeOH);UV(MeOH)λmax(logε)433(),249(),202()nm;CD(MeOH)Δε210+,Δε225+,Δε265?,Δε362+;ESIMSm/z423[M?H]?,HRESIMSm/??113[MH](calcdforC28H39O3,).MRdata,seeTable1.(12)Wang,S.;Zhang,L.;Liu,.;Dong,.;Li,.;Liu,,2,240?244.(13)Nes,.;Varkey,.;Crump,.;Gut,M..,41,3429?3433.(14)Mijares,A.;Cargill,.;Glasel,.;Lieberman,S..,32,810?812.(15)Fujimoto,Y.;Kimura,M.;Khalifa,.;Ikekawa,,32,4372?4381.(16)Rubinstein,L.;Goad,,13,485?487.(17)Gawas,D.;Garcia,R.;Huch,V.;Muller,,74,1281?1283.(18)Ha,.;Kokke,.;Djerassi,,40,433?453.(19)Kob

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