Dragonamide和Leucamide A的全合成研究.pdf

1、Ip—業(yè)!攀⑨天畢大驀中國近代第一所大學博士學位論文一級學科；化學工程與技術(shù)學科專業(yè)：應(yīng)用化學作者姓名：陳宏亮指導(dǎo)教師：馮亞青教授2004年12月——奎堡奎蘭堡主蘭焦堡皇AbstractDragonamide，anoceanicnaturematerial，wastotalsynthesizedinthepaperAndfragmentsofLeucamideA，artoceanicnaturematerialtoo，weresynth

2、esizedSynthesisroutetoDragonamidewasdesignedThemoleculeWaSmadeupwithTetrapeptideA15and(只)一2一methyl7alkyl—octylacid，A28TheywerecoupledusingBOPCIascouplingreagenttogiveA30AftercleavageofthetbutylesterofA30，Dragonamidewasac

3、hievedbyactivationwithPyBOPandtreatmentwithammoniainayieldof1O，9％TetrapeptideA15waspreparedfromLPheandLValinayieldof325％withOnitrobenzenesulfonylgroupandtButylgroupasprotectinggroups(R)一2methyl7alkyloctylacid，A28wasprepa

4、redfrom1，5pentanedi01AftermonoprotectionandSwemoxidation，aldehydewasgotThenitreactedwithwittigreagentAfterselectivehydrogenationandhydrolyzation，theintermediatewascouplingwithchiralauxiliaryThenalkylationofstereoselectiv

5、ewascompletedwithNAHMDSAandMelat一78℃Chiralauxiliar)，wasremoved，followedbyesterificafionwithdiazomethane，hydrogenationandSwernoxidationtogiveanotheraldehydeItwasconvertedalkyneusingtheOhira—Bestmannreagentf月)一2一methyl7一al

6、kyloctylacid，A28wasgotaftersaponificationinayieldof171％andeebeyond99％DuetoitsNMRandopticalrotationdatacouldnotmatchtheminreference，itwasfoundthatstructureofdragonamidewaswrongThenf趴一2一methyl7一alkyloctylacidwaspreparedusi

7、ngexactlythesameprocedureAndcorrectdragonamidewassynthesizedatfinallyinatotalyieldof186％，andstmcturewasSSSSSnotRSSSSSynthesisroutetOLeucamideAwasdesignedThemoleculewasmadeupwithB12B20andB24whichwerepreparedinpaperB12wasg

8、ivenfromcouplingafterremovingprotectinggroupsofB10andB6DipeptideB10wasobtmnedfromL—LeuandLProinayieldof567％InasimilarwayDipeptideB4wasobtainedfromL—SerandLAlaAftercyclodehydratjonwithBurgessreagenlanddehydrogenationwithB

9、rCCl3&DBU，theoxazoleB6waspreparedinayieldof468％B20wasobtmnedafterremovingprotactinggroupofB19DipeptideB17wasobtainedfromL—SerandLThrthroughsimilarway，followedbyoxidationwithDess—MartinPeriodinaneandcyclodehydrationwithPP