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1、第六部分第六部分合成计划的考察和选择合成计划的考察和选择考察的基本原则考察的基本原则1.设计的合成路线要高效、简洁。2.包含新奇的化学问题或已知化学的新应用。3.可提供相当量的目标化合物。4.竞争中具有时间或化学优势。全合成的目的全合成的目的::1.确定或论证结构；2.提供样品；3.合成衍生物；4.发展新反应和新的化学理论；5.强调目标分子导向的各种复杂体系应用；6.发展学科、训练培养人才。一、确证复杂结构（一、确证复杂结构（11））OHSCOOHSOHLipoxinASOHAcOOAcOOClOAcClOAcOHOHPUG412-e
2、pi-PUG3确证复杂结构（确证复杂结构（22））OHOHOHOHCCHOOHCCHOOHCCHOHOOHOOHOOIIIRobustdial(III)OOOCOHOCOHHHOEtOEtEtOOOOHHHOOOEtOHIVSpecioninV确证结构的历史发展确证结构的历史发展•Formanyyearsthemainroleoftotalsynthesiswastoprovidethefinalandconclusiveproofofstructure.•Afterlate1960s,withtheadventofroutineX-
3、raycrystallographyandhigh-fieldFT-NMR,chemicaldegradationallbutdisappeared.•Now,thenaturalproductsynthesisisaprimaryplatformforbasicdiscoveryinorganicchemistry.•Mischaracterizationofstructuresisstilloftenexisting,whichneedsthetotalsynthesistoverifyit.TheStoryofTheStoryo
4、fLepadiformineLepadiformineWeinreb,Acc.Chem.Res.2003,36(1),59.ModerateinvitroMorestableconformationcytotoxicactivityagainstbymolecularmechanismseveraltumorcelllines.calculation.HAHHC6H13CBNCHHN613NHHHOC6H13HHOOLepadiformine(1)1a1bby1HNMR&13CNMRBiard,TetraLett.1994,35,26
5、91.A/Bcis-1-azadecalin;UnusualSuggestedconformationzwitterionicvicinalaminobyinitialNMRnOe.alcoholmoiety.LepadiformineLepadiformine::StructuralrelationshipStructuralrelationshipHHC6H13ACNH1056H13RNcyclindricines/HHlepadiformineCNHHOHOHPO1a1bLepadiformine(1a)Lepadiformin
6、e(1b)Biard,TetraLett.1994.byMMcalculation.OHOOHNHHC6H13ClNHC6H13N14HClHC6H13R78cyclindricineB2R=ClcyclindricineARatioof2/8=3:2insolution3R=OHcyclindricineC4R=OMecyclindricineD5R=OAccyclindricineE6R=SCNcyclindricineFBlackman,etal.Tetrahedron1993,49,8645.LepadiformineLepa
7、diformine::DisproofoftheDisproofoftheBiardBiardstructureviastructureviasynthesis(1)synthesis(1)------WeinrebWeinreb’’ssynthesisssynthesisHHC6H13NCHH613NHHHOHO1a1bLepadiformine(1)by1HNMR&13CNMRBiard,TetraLett.1994,35,2691.DMSOH1950C5NOHO3NHClC108steps6H1363%C6H13ONOC6H13
8、NOHNHOHHHPhOPhOPhOOOC6H132stepsC6H13ONHNC6H13NHHHHHHPhOPhOPhOC6H13C6H13C6H13113Li-NH3,EtOHHNMRandCNMRwerediffe
