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1、第六部分合成计划的考察和选择1©2004YZJ-SIOC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。2©2004YZJ-SIOC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。3©2004YZJ-SIOC一、确证复杂结构（1）OHSCOOHSOHLipoxinASOHAcOOAcOOClOAcClOAcOHOHPUG41
2、2-epi-PUG34©2004YZJ-SIOC确证复杂结构（2）OHOHOHOHCCHOOHCCHOOHCCHOHOOHOOHOOIIIRobustdial(III)OOOCOHOCOHHHOEtOEtEtOOOOHHHOOOHOEtIVSpecioninV5©2004YZJ-SIOC确证结构的历史发展¢Formanyyearsthemainroleoftotalsynthesiswastoprovidethefinalandconclusiveproofofstructure.¢Afterlate1960s,withtheadve
3、ntofroutineX-raycrystallographyandhigh-fieldFT-NMR,chemicaldegradationallbutdisappeared.¢Now,thenaturalproductsynthesisisaprimaryplatformforbasicdiscoveryinorganicchemistry.¢Mischaracterizationofstructuresisstilloftenexisting,whichneedsthetotalsynthesistoverifyit.6©2004
4、YZJ-SIOCTheStoryofTheStoryofLepadiformineLepadiformineWeinreb,Acc.Chem.Res.2003,36(1),59.ModerateinvitroMorestableconformationcytotoxicactivityagainstbymolecularmechanismseveraltumorcelllines.calculation.HAHHC6H13CBNCHHN613NHHHOC6H13HHOOLepadiformine(1)1a1bby1HNMR&13CNM
5、RBiard,TetraLett.1994,35,2691.A/Bcis-1-azadecalin;UnusualSuggestedconformationzwitterionicvicinalaminobyinitialNMRnOe.alcoholmoiety.7©2004YZJ-SIOCLepadiformineLepadiformine::StructuralrelationshipStructuralrelationshipHHC6H13ACNH1056H13RNcyclindricines/HHCNHlepadiformin
6、eHOHOHPO1a1bLepadiformine(1a)Lepadiformine(1b)Biard,TetraLett.1994.byMMcalculation.OHOOHNHHC6H13ClNHC6H13N14HHC6H13ClR78cyclindricineB2R=ClcyclindricineARatioof2/8=3:2insolution3R=OHcyclindricineC4R=OMecyclindricineD5R=OAccyclindricineE6R=SCNcyclindricineFBlackman,etal.
7、Tetrahedron1993,49,8645.8Lepadiformine:DisproofoftheBiardstructure©2004YZJ-SIOCviasynthesis(1)---Weinreb’ssynthesisHHC6H13NCHH613NHHHOHO1a1bLepadiformine(1)by1HNMR&13CNMRBiard,TetraLett.1994,35,2691.DMSOH1950C5NOHO3NHClC108steps6H1363%C6H13ONOC6H13NOHNHOHHHPhOPhOPhOOOC6
8、H132stepsC6H13ONHNC6H13NHHHHHHPhOPhOPhOC6H13C6H13C6H13113Li-NH3,EtOHHNMRandCNMRweredifferent+NNNaswellasitsHCl
