天然药物化学第二讲.ppt

天然药物化学第二讲.ppt

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IntroductiontotheStudiesofBiosynthesisofNaturalProducts,YuemaoS,CollegeofPharmaceuticalSciences,ShandongUniversitySeptember13,2010,3.Threeexamples,TheBiosynthesisofTaxol,Techniquesweapplied:

A.Stableisotopelabeling,feedingB.RadioactiveisotopetracinginEnzymaticacetylationConclusion:

10-deacetylbaccatin-IIIisaprecursoroftaxol,Hypotheticmultiplepathwaystowardstaxol,ThebiosynthesisofrifamycinB,Twopossiblepathways,AandB,towardsrifamycinB.AdemandedthatprotorifamycinIisthekeyintermediateandtheoxygenattheC-8positionisintroducedlater.BrequiredthattheoxygenatC-8isofthesameoriginasthecarbonofC-8,i.e.,fromthecarboxylgroupofAHBA.,MethodsandTechiques:

DNAmutagensis;stableisotopelabeling,feeding;13CNMRassay;LC-ESI-MSConclusions:

A.TheC-8oxygenisthesameoriginastheC-8carbonB.TheformationofnaphthoquinoneprecedesthelactamizationC.ThebiosynthesisoftypeIpolyketidesoccursprogressively,Thesequenceoftheformationofthenaphthoquinoneandlactam,ThebiosynthesisofStreptomycessporepigment,OriginsofBuildingBlocks,CommonBuildingBlocks,C1,C2,C5,CommonBuildingBlocks,C6C3,C6C2,C6C1,C6C2N,CommonBuildingBlocks,C4N,C5N,Indole-C2N,CommonFAs,AcylThioester,GeneralChemistry,AldolandClaisenCondensation,AldolandClaisenCondensation,AldolandClaisenCondensation,MalonylCoA:

activatedacetylCoA,MalonylCoA:

activatedacetylCoA,OverallBiosyntheticScheme,BacterialAromaticPolyketides,BacterialAromaticPolyketides,BacterialAromaticPolyketides,BacterialReducedPolyketides,A,Acetate;P,Propionate;B,Butyrate;G,Glycerol;S,Starterfrombranchedchainorcyclicunits,BacterialReducedPolyketides,BacterialReducedPolyketides,FungalAromaticPolyketides（Non-reduced/PartiallyReducedPolyketides）,Orsellinicacid,Tetrahydroxynaphthalene（THN）,6-Methylsalicylicacid（MSA）,Norsolorinicacid,FungalAromaticPolyketideswithunusualfeatures-mixedreduced/non-reduced,UnusualacetatelabelUnusualstarterUnusualmix,FungalHighlyReducedPolyketides,T-toxin,Mevacor,Statins,hydroxy-methylglutaryl-CoA（HMG-CoA）.,FungalAromaticPolyketides（Non-reduced/PartiallyReducedPolyketides）,Orsellinicacid,Tetrahydroxynaphthalene（THN）,6-Methylsalicylicacid（MSA）,Norsolorinicacid,PlantPolyketides（BacterialpolyketidesmadebythesametypeofPKS）,chalconeinhigherplants,1,3,6,8-tetrahydroxynaphthalene（THN）inStreptomycesgriseusandS.coelicolor,3,5-dihydroxyphenylaceticacid（DHPA）inAmycolatopsismediterraneiandA.orientalis,PlantPolyketides（Starter:

PhenylpropanhoidPathway）,chalcone,PlantPolyketides（BacterialpolyketidesmadebythesametypeofPKS）,chalconeinhigherplants,1,3,6,8-tetrahydroxynaphthalene（THN）inStreptomycesgriseusandS.coelicolor,3,5-dihydroxyphenylaceticacid（DHPA）inAmycolatopsismediterraneiandA.orientalis,NonribosomalPeptides,Antibiotics,NonribosomalPeptides,Antibiotics,NonribosomalPeptides,Immunosuppresants,NonribosomalPeptides,Toxins,NonribosomalPeptides,NonribosomalPeptides,NonribosomalPeptides,NonribosomalPeptides,NonribosomalPeptides,NonribosomalPeptides,Antibiotics,NonribosomalPeptides,Antibiotics,NonribosomalPeptides,Lastresortforagainstdrug-resistantpathogens,NonribosomalPeptides,HybridNRP-PK,NonribosomalPeptides,HybridNRP-PK-C-aminated,NonribosomalPeptides,HybridNRP-PK-N-acylated,NonribosomalPeptides,