天然药物化学第二讲.ppt

天然药物化学第二讲.ppt

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IntroductiontotheStudiesofBiosynthesisofNaturalProductsYuemaoSCollegeofPharmaceuticalSciences,ShandongUniversitySeptember13,20103.ThreeexamplesTheBiosynthesisofTaxolTechniquesweapplied:

A.Stableisotopelabeling,feedingB.RadioactiveisotopetracinginEnzymaticacetylationConclusion:

10-deacetylbaccatin-IIIisaprecursoroftaxolHypotheticmultiplepathwaystowardstaxolThebiosynthesisofrifamycinBTwopossiblepathways,AandB,towardsrifamycinB.AdemandedthatprotorifamycinIisthekeyintermediateandtheoxygenattheC-8positionisintroducedlater.BrequiredthattheoxygenatC-8isofthesameoriginasthecarbonofC-8,i.e.,fromthecarboxylgroupofAHBA.MethodsandTechiques:

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

A.TheC-8oxygenisthesameoriginastheC-8carbonB.TheformationofnaphthoquinoneprecedesthelactamizationC.ThebiosynthesisoftypeIpolyketidesoccursprogressivelyThesequenceoftheformationofthenaphthoquinoneandlactamThebiosynthesisofStreptomycessporepigmentOriginsofBuildingBlocksCommonBuildingBlocksC1C2C5CommonBuildingBlocksC6C3C6C2C6C1C6C2NCommonBuildingBlocksC4NC5NIndole-C2NCommonFAsAcylThioesterGeneralChemistryAldolandClaisenCondensationAldolandClaisenCondensationAldolandClaisenCondensationMalonylCoA:

activatedacetylCoAMalonylCoA:

activatedacetylCoAOverallBiosyntheticSchemeBacterialAromaticPolyketidesBacterialAromaticPolyketidesBacterialAromaticPolyketidesBacterialReducedPolyketidesA,Acetate;P,Propionate;B,Butyrate;G,Glycerol;S,StarterfrombranchedchainorcyclicunitsBacterialReducedPolyketidesBacterialReducedPolyketidesFungalAromaticPolyketides（Non-reduced/PartiallyReducedPolyketides）OrsellinicacidTetrahydroxynaphthalene（THN）6-Methylsalicylicacid（MSA）NorsolorinicacidFungalAromaticPolyketideswithunusualfeatures-mixedreduced/non-reducedUnusualacetatelabelUnusualstarterUnusualmixFungalHighlyReducedPolyketidesT-toxinMevacorStatinshydroxy-methylglutaryl-CoA（HMG-CoA）.FungalAromaticPolyketides（Non-reduced/PartiallyReducedPolyketides）OrsellinicacidTetrahydroxynaphthalene（THN）6-Methylsalicylicacid（MSA）NorsolorinicacidPlantPolyketides（BacterialpolyketidesmadebythesametypeofPKS）chalconeinhigherplants1,3,6,8-tetrahydroxynaphthalene（THN）inStreptomycesgriseusandS.coelicolor3,5-dihydroxyphenylaceticacid（DHPA）inAmycolatopsismediterraneiandA.orientalisPlantPolyketides（Starter:

PhenylpropanhoidPathway）chalconePlantPolyketides（BacterialpolyketidesmadebythesametypeofPKS）chalconeinhigherplants1,3,6,8-tetrahydroxynaphthalene（THN）inStreptomycesgriseusandS.coelicolor3,5-dihydroxyphenylaceticacid（DHPA）inAmycolatopsismediterraneiandA.orientalisNonribosomalPeptidesAntibioticsNonribosomalPeptidesAntibioticsNonribosomalPeptidesImmunosuppresantsNonribosomalPeptidesToxinsNonribosomalPeptidesNonribosomalPeptidesNonribosomalPeptidesNonribosomalPeptidesNonribosomalPeptidesNonribosomalPeptidesAntibioticsNonribosomalPeptidesAntibioticsNonribosomalPeptidesLastresortforagainstdrug-resistantpathogensNonribosomalPeptidesHybridNRP-PKNonribosomalPeptidesHybridNRP-PK-C-aminatedNonribosomalPeptidesHybridNRP-PK-N-acylatedNonribosomalPeptides