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1、MeMeOMeAcOMeMeOOOHOHONaHO3POOHNNMeHOOOHOMeOHOHSeekingGeneralYetSelectiveReactionsNOHOHMeEricJacobsenHONHHH2OMeMeMeOOH2NCNCO2HHHHarvardUniversityNCO2HMeMeMeHOOOOMeWuXiAppTecCHOHMay12,2010O3HNH25C12H3COOOOHNOHOHOHOOHMeCH3CHOMe3Top-SellingPharmaceuticalsProductWaste“EFactor
2、”BulkChemicals<1–5104-106tFineChemicals5–50102-104tPharmaceuticals25–>10010-103tR.SheldonPureAppl.Chem.2000,72,1233TheJacobsenGroupMethodsSynthesis•"important"innovativeandefficienttransformationssynthesisofsimple•generalandandcomplextargetsselectivereactionsCatalysisMec
3、hanism•understandinghowsmallmolecule-catalystswork•newreactivityphenomena•cooperativityeffectsEnzymesandSmallMoleculeCatalystsEnzymesandSmallMoleculeCatalystsCF3OF3CNNHHRHNROSt-BuHNNNCBzo-NO2C6H4SO3H+ArNCBzAr90-98%ee(14examples)Whenwestartedthisworkweexpectedtheseman-mad
4、esystemstohaveahighlyspecificmatchbetweensubstrateandligand,justlikeenzymes.Generally,inourhandsandinthehandsofthosethatfollowedus,agoodcandidatehasbeenusefulforquitearangeofapplications.W.S.Knowles(NobelLecture)Angew.Chem.Int.Ed.2002,41,1998TPYoon,ENJacobsenScience2003,
5、299,1691Salen:APrivilegedChiralLigandReview:JFLarrow,ENJacobsenTopicsOrganometChem2004,6,123-152HHNNAlt-BuOOt-BuOXOt-But-BuX+NuHNHCOPhRRNuOOOOONHCOPhNHCOPhNCNHCOPhNHCOPhNHCOPhCNCNn-Prt-BuN3MeCNi-PrMeO2CCO2MeCNFOONOMeO2CNPMBNHCOPhOOMeCO2Eti-PrNNNNHCOPhNHCOPhMe2SiCNPhNNNNt
6、-BuSNNSMePhPhNOOOONHCOPhCH3NCNMeMeMeNPhn-PrNNSO2PhPhNO2i-PrN3CombiningBuildingBlockswithDiastereoselectiveReactions:AsymmetricCatalyticSynthesesofQuinineandQuinidineOOOH2,Raney-NiNHCOPhNHCOPhTol/MeOHNH(salen)AlIIICNTBSOTBSOTBSO+HCO2MeCO2MeNCCO2Me92%ee,97%yOMeOMedeprotect
7、,CBzNΔNNOHADmix-β,OMeOFGINCBzquinineNNOMeOHADmix-α,deprotect,CBzFGINΔNNNOOMequinidineITRaheem,SNGoodman,ENJacobsenJACS2004,118,706TotalSynthesisofLactacystinOOMeMeONHBnNClMeNHHOHOHSOCO2EtMeMeAcHNCNOHOHOCO2HlactacystinsalinosporamideAIsolationandstructurereportedbyOmuraet
8、alIsolationandstructurereportedbyFenicaletalJAntibiot1991,44,113JAntibiot1991,44,117AngewChemIntEd2003,