AssociateInvestigatorandDirectorofChemistryCenter,NIBS,Beijing,ChinaPhone：010-8070-4786
Fax：010-80704785
E-mail：leixiaoguang@nibs.ac.cn
GroupWebsite:http://www.nibs.ac.cn/xlei/home.htm
教育经历Education:2001北京大学，化学与分子工程学院，化学学士学位
B.S.inChemistry,PekingUniversity,Beijing,China
2006美国波士顿大学，化学系，有机化学博士学位
Ph.D.inOrganicChemistry,BostonUniversity,Boston,USA
工作经历ProfessionalExperience:2013-present北京生命科学研究所高级研究员,化学中心主任
AssociateInvestigatorandDirectorofChemistryCenter,NIBS
2008-2012北京生命科学研究所研究员,化学中心主任
AssistantInvestigatorandDirectorofChemistryCenter,NIBS
2006-2008美国哥伦比亚大学，美国斯隆-凯特林癌症研究中心，博士后
PostdoctoralFellow,ColumbiaUniversityandMemorialSloan-KetteringCancerCenter(MSKCC),NewYork,USA
研究概述：小分子影响了许多重要的生物过程，因此它们可以被认为是“中心法则”的另一个重要的组成成分。具有生物活性的小分子可以是通过自然进化选择的天然产物，也可以是通过有机合成制造的药物分子和用于研究生物进程的化学探针。因此有机合成是化学学科中的重要分支，与药物研发，以及生命科学研究密切相关。当前，我们急需应用新的小分子去帮助研究已知的生物反应机理，去发现尚未被阐明的生物作用机理，去验证全新的生物药物靶点，和去解决重大的医学难题。特别是当前创新型药物研究进入到一个多学科、多技术协作的新时代。其中化学，特别是有机合成，药物化学与化学生物学，和生命科学的结合是满足创新型药物研发的先决条件。因此，我们实验室的主要研究方向包括以下三个方面：1）对于具有重要生物功能和复杂结构的天然产物的全合成；2）运用天然产物和其他具有生物活性的小分子作为分子探针进行化学生物学研究，从而发现新的生物靶点和阐明新的生物作用机制；3）寻找和发现新的药物靶点，利用药物化学手段设计并且合成相关小分子进行创新药物的研究。4）发展新一代的生物正交反应，并且应用在化学生物学研究中。ResearchDescriptionManycriticalbiologicalprocessesareconductedbysmallmoleculesandsotheycanarguablyberegardedasanotheressentialcomponentofthe“centraldogma”ofmolecularbiology.Biologicallymeaningfulsmallmoleculesmaybenaturalproducts,whicharediscoveredbynaturethroughmanycyclesofdiversitygenerationandnaturalselection,ortheymaybepreparedthroughorganicsynthesisforthedevelopmentofdrugcandidatesorchemicalprobestostudylife’sprocesses.Therefore,organicsynthesisisanimportantdisciplinethatcontinuestoplayavitalroleindrugdiscoveryandinthealliedfieldsofmedicineandbiology.Newsmallmoleculesareneededtofunctionasprobestofurtherstudytheknownbiologicalpathways,todiscovernovelpathwaysandinteractions,tovalidatepotentialdrugtargets,andtotreatunmetmedicalneedsasdrugs.Accordingly,thecentralthemeofourresearchfocusesontheefficientsynthesisofthesesmallmolecules,aswellasthesubsequentbiologicalevaluationsofthesemoleculesapplyingmedicinalchemistryandchemicalbiologyapproaches.WealsohopetofacilitatethesynergybetweensyntheticchemistryandbiologicalsciencesatNIBSbycreatingaresearchenvironmentinwhichnewscientificcollaborationsarepossible.发表文章Publications1.Li,Q.;Dong,T.;Liu,X.;Lei,X.*“ABioorthogonalLigationEnabledbyClickCycloadditionofo-QuinolinoneQuinoneMethideandVinylThioether”J.Am.Chem.Soc.2013,DOI:10.1021/ja401989p.2.Li,C.;Dong,T.;Dian,L.;Zhang,W.;Lei,X.*“BiomimeticSynthesesandStructuralElucidationoftheApoptosis-InducingSesquiterpenoidTrimers:(-)-AinsliatrimersAandB”Chem.Sci.2013,4,1163-1167.3.Wang,G.;Wang,X.;Yu,H.;Wei,S.;Williams,N.;Holmes,D.L.;Halfmann,R.;Naidoo,J.;Wang,L.;Li,L.;Chen,S.;Harran,P.;Lei,X.*;Wang,X.*“SmallMoleculeActivationoftheTRAILReceptorDR5inHumanCancerCells”Nat.Chem.Biol.2013,2,84-90.(NewsstoriesdescribingthisworkwerehighlightedinChem.&Eng.News2013,2,37;NatureAsia2012,December24).4.Huang,J.;Lei,X.*“ANature-inspiredConciseSynthesisof(+)-ent-Chromazonarol”Sci.ChinaChem.2013,56,349-353.5.Li,H.;Wang,X.;Hong,B.;Lei,X.*“CollectiveSynthesisofLycopodiumAlkaloidsandTautomerLockingStrategyfortheTotalSynthesisof(-)-LycojapodineA”J.Org.Chem.2013,78,800-821.(FeaturedandCoverArticle).6.Li,C.;Li,X.;Wang,X.;Lei,X.*“Diversity-OrientedSynthesisofBicyclicRingSystemsviaaConjugateAddition/Aldol/RCMProcess”Sci.ChinaChem.2013,56,337-341.7.Li,C.;Dian,L.;Zhang,W.;Lei,X.*“BiomimeticSynthesesof(-)-GochnatiolidesA-Cand(-)-AinsliadimerB”J.Am.Chem.Soc.2012,134,12414-12417.8.Lei,X.*;Li,H.“SelectiveAlkeneMetathesisintheTotalSynthesisofComplexNaturalProduct”Top.Curr.Chem.2012,327,163-196.9.Sun,L.;Wang,H.;Wang,Z.;He,S.;Chen,S.;Liao,D.;Wang,L.;Yan,J.;Liu,W.;Lei,X.*;Wang,X.*“MixedLineageKinaseDomain-likeProteinMediatesNecrosisSignalingDownstreamofRIP3Kinase”Cell2012,148,213-227.(NewsstoriesdescribingthisworkwerehighlightedinChem.&Eng.News2012,5,40;NatureChina2012,February1;AsianScientist2012,January31;andNatureReviewsMolecularCellBiology,2012,Feb.8).10.Li,H.;Wang,X.;Lei,X.*“TotalSynthesesofLycopodiumAlkaloids(+)-Fawcettimine,(+)-Fawcettidineand(-)-8-Deoxyserratinine”Angew.Chem.Int.Ed.2012,51,491-495;Angew.Chem.2012,124,506-510.11.Liao,D.;Li,H.;Lei,X.*“EfficientGenerationofortho-QuinoneMethide:ApplicationtotheBiomimeticSynthesesof(±)-ScheffloneandTocopherolTrimers”Org.Lett.2012,14,18-21.12.Li,C.;Tu,S.;Wen,S.;Li,S.;Chang,J.;Shao,F.;Lei,X.*“TotalSynthesisoftheG2/MDNADamageCheckpointInhibitorPsilostachyinC”J.Org.Chem.2011,76,3566-3570.13.Chou,T.;Dong,H.;Zhang,X.;Lei,X.;Hartung,J.;Zhang,Y.;Lee,H.L.;Wilson,R.M.;Danishefsky,S.J.*“MultifacetedCytoprotectionbySyntheticPolyacetylenesInspiredbytheGinseng-derivedNaturalProductPanaxytriol”Proc.Natl.Acad.Sci.USA2011,108,14336-14341.14.Li,C.;Yu,X.;Lei,X.*“ABiomimeticTotalSynthesisof(+)-AinsliadimerA”Org.Lett.2010,12,4284-4287.15.Gong,Y.;Wang,X.;Wang,J.;Yang,Z.;Li,S.;Yang,J.;Liu,L.;Lei,X.*;Shao,F.*“ChemicalProbingRevealsInsightsintotheSignalingMechanismofInflammasomeActivation”CellRes.2010,20,1289-1305.16.Han，Z.;Niu,T.;Chang,J.;Lei,X.;Zhao,M.;Wang,Q.;Cheng,W.;Wang,J.;Feng,Y.;Chai,J.*“CrystalstructureoftheFTOproteinrevealsbasisforitssubstratespecificity”Nature2010,464,1205-1209.17.Lee,L.S.;Stephenson,K.K.;Fahey,J.W.;Parsons,T.L.;Lietman,P.S.;Andrade,A.S.;Lei,X.Yun,H.;Soon,G.H.;Shen,P.;Danishefsky,S.J.*;Flexner,C.*“InductionofChemoprotectivePhase2EnzymesbyGinsenganditsComponents”PlantaMed.2009;75,1129-113318.Lei,X.;Danishefsky,S.J.*“EfficientSynthesisofaNovelResorcyclideasAnticancerAgentBasedonHsp90Inhibition”Adv.Synth.Catal.2008,350,1677-168119.Lei,X.;Dai,M.;Hua,Z.;Danishefsky,S.J.*“BiomimeticTotalSynthesisofTricycloillicinoneandMechanisticStudiesTowardtheRearrangementofPrenylPhenylEthers”TetrahedronLett.2008,49,6383-638520.Ng,F.;Yun,H.;Lei,X.;Danishefsky,S.J.;Fahey,J.;Stephenson,K.;Flexner,C.;Lee,L.*“(3R,9R,10R)-Panaxytriol:amolecular-basednutraceuticalwithpossibleapplicationtocancerpreventionandtreatment”TetrahedronLett.2008,49,7178-717921.Peng,L.F.;Kim,S.S.;Matchacheep,S.;Lei,X.;Su,S.;Lin,W.;Runguphan,W.;Choe,W.H.;Sakamoto,N.;Beeler,A.B.;Porco,J.A.,Jr.;Schreiber,S.L.*andChung,R.T.*“IdentificationofNovelEpoxideInhibitorsofHCVReplicationUsingHigh-ThroughputScreening.”Antimicrob.AgentsChemother.2007,51,3756-3759.22.Lei,X.;Porco,J.A.,Jr.*“TotalSynthesisoftheDiazobenzofluoreneAntibiotic(-)-KinamycinC.”J.Am.Chem.Soc.2006,128,14790-14791.(NewsstorydescribingthisworkwashighlightedinChem.&Eng.News2006,45,9.)23.Porco,J.A.,Jr.*;Su,S.;Lei,X.;Bardhan,S.;Rychnovsky,S.D.“TotalSynthesisandStructureAssignmentof(+)-Hexacyclinol”Angew.Chem.Int.Ed.2006,45,5790-5792;Angew.Chem.2006,118,5922-5924.(NewsstoriesdescribingthisworkwerereportedinChem.&Eng.News2006,31,11andNature2006,442,492-493)24.Lei,X.;Zaarur,N.;Sherman,M.Y.;Porco,J.A.,Jr.*“StereocontrolledSynthesisofaComplexChemicalLibraryviaElaborationofAngularEpoxyquinolScaffolds.”J.Org.Chem.2005,70,6474-6483.25.Su,S.;Aquilano,D.;Arumugasamy,J.;Beeler,A.B.;Eastwood,E.L.;Giguere,J.R.;Lan,P.;Lei,X.;Min,G.K.;Yeager,A.R.;Zhou,Y.;Panek,J.S.;Snyder,J.K.;Schaus,S.E.;Porco,J.A.,Jr.*“ConvergentSynthesisofaComplexOximeLibraryUsingChemicalDomainShuffling.”Org.Lett.2005,7,2751-2754.26.Lei,X.;Porco,J.A.,Jr.*“SynthesisofaPolymer-SupportedAnthraceneandItsApplicationasaDienophileScavenger.”Org.Lett.2004,6,795-798.27.Lei,X.;Johnson,R.P.;Porco,J.A.,Jr.*“TotalSynthesisoftheUbiquitin-ActivatingEnzymeInhibitor(+)-Panepophenanthrin.”Angew.Chem.Int.Ed.2003,42,3913-3917;Angew.Chem.2003,115,4043-4047.(Thispublicationwashighlightedasa“HotPaper”.)发表专利Patents1.Danishefsky,S.J.;Yun,H.;Chou,T.;Lei,X.;Sames,D.“Compoundsandmethodsfortreatingcancerorneurotrophicdisorder.”US2011/01246902.Danishefsky,S.J.;Chou,T.;Lei,X.;Yun,H.;Ng,F.;Hartung,J.;Sames,D.“Compounds,compositionsandmethodsforreducingtoxicityandtreatingorpreventingdiseases.”PCTInt.Appl.2010,WO20100252723.Danishefsky,S.J.;Chou,T.;Lei,X.“Compounds,compositionsandmethodsfortreatingorpreventingdiseases.”PCTInt.Appl.2009,WO20091051234.Cottarel,G.;Gardner,T.;Lei,X.;Porco,J.;Schaus,S.;Wierzbowski,J.“CompositionsandmethodsforpotentiatingantibioticactivityusinganATPreceptorantagonist,coumarin,flavone,orterpene”PCTInt.Appl.,2008,WO20080192925.Danishefsky,S.J.Lei,X.;Yun,H.;Chou,T.“Compositionsandmethodsusingapanaxytriolcompoundincombinationwithatubulin-bindingdrugfortreatingcanceroraneurotrophicdisorder.”PCTInt.Appl.2008,WO2008103916
