酶促-化學(xué)法合成核苷類藥物衍生物及其高分子前藥.pdf

1、浙江大學(xué)理學(xué)院碩士學(xué)位論文酶促化學(xué)法合成核苷類藥物衍生物及其高分子前藥姓名：夏愛華申請學(xué)位級別：碩士專業(yè)：化學(xué)指導(dǎo)教師：吳起20070901AbstractEnzymaticmethodsplayallimportantroleinthesynthesisofpharmaceuticalcompoundsandtheirderivativesduetotheirhi曲selectiV竹andmildreactionconditionsI

2、nthisthesis，selectiveenzymaticsynthesisofnucleosidedrugderivativeswasdevelopedTheselectiveenzymaticsynthesisofsomenucleosidederivativescontainingmulti—hydroxylinnonaqueousmediaWasdeveloped2deoxy5fluorouridine，5fluorourid

3、ine，5fluorocytidineand5deoxy一5fluorouridinewerechosenassubstratesDivinyldicarboxylateswithdifferentlengthofcarbonchainwereusedasacyldonorPolymerizablevinylestersderivativesofdrugswereselectivelypreparedingoodyieldsandsel

4、ectivitythroughenzymaticreactionMoreovertheinfluencefactorsofenzymaticsynthesissuchasenzymesources，reactionmediawatercontent，reactiontime，temperaturewereinvestigatedThecontrollableselectivesynthesisof2’deoxy一5一fluorourid

5、inederivativescouldbeachievedCatalysisbylipaseacrylicresinfromCandidaantarctica(CAL—B)iIlnForalkalineproteasefromBacillussubtilis(Subtilisin)inpyridinecouldfacilitatethesinglestepsynthesisofpolymerizable2deoxy5fluorourid

6、inederivativesinhi曲yieldsThecontrollableselectivityofdifferentpositionof2deoxy5fluomuridinewasachievedbychangereactionconditionsFurthermore，selectiveacylationofprimaryhydroxylof5fluorouridineand5fluorocytidineWasachieved

7、ThereactionWascatalyzedbyCAL—BinTHFAndtheenzymaticselectiveacylationof5deoxy一5一fluorouridineWasunderinvestigationtoo。Floxuridinesaccharideand5fluorouridineconjugates，whichalepotentialtargetingdrugs，wereobtainedfromvinyln