面包酵母轉化大茴香醛合成手性醫(yī)藥中間體初探

1、江南大學碩士學位論文面包酵母轉化大茴香醛合成手性醫(yī)藥中間體初探姓名：閆薇薇申請學位級別：碩士專業(yè)：微生物與生化藥學指導教師：湯魯宏陳偉20080601AbstractAbstractpAnisaldehyde(p—CH30C6H4CHO，MW：136，15，CASNo1231l一5)，isaki蕊ofanalogofbenzaldehydefoundfromnaturalresourcesItcallbebiotransformedtO

2、achimlproductpMeO—BenzylAlcohol(pMeOBA)andchiralproduct(1震)一1hydroxy1(4一methoxyphenyl)propan2一one(Lp—MeOPhenylAcetylCarbinol，LpMeOPAC)bytheAlcoholDehydrogenase(hDH)andthe哪ateDecarboxylase(PDC)existedintheyeastrespectivel

3、yAndtheLp—MeOPACcarlbefurthertransformedto(一)一(1R，2s)l一(4Methoxyphenyl)Propanel，2一Diol◇一MeO—PPDA)，thekeychiralintermediateforthesynthesisof冰)一Tamsulosin，adrugusedforthesymptomatictreatmentofbenignprostatichyperplasiaInor

4、dertegulatetherelativeactivityofAD囂andPDCcoexistedinthewholecellofyeastmediatedbiotransformationsystemtowardsthesubstrateofPanisaldehydeandimprovethechiralpharmaceuticalintermediateproductionespeciallytheproductofPMeO—PP

5、DA，thebitransformationsystemwasoptimized，fromtheaspectsofyeastspecies，temperature，biotransformationtime，concentrationofsucrose，concentrationofPanisaldehyde，cellactivationtime，initialpH，rotaryspeed，acetaldehyde，auxiliarys

6、olvents，cellimmobilization，withthehelpofTLC，colorimetryandGC／MSanalysisAndfinally，thechiralproductofp—MeO—PPDAWaSseparated，purifiedandcrystallized翻鏘purityofthecrystalswascheckedandthestructureidentificationwascarriedoutc

7、onsequently曩瓣optimizedreactionconditionswereasfollows：baker’SyeastwastheidealyeasttOtransformpanisaldehydeintochiralproducts，foritslowertemperaturerequirements(294C)，shorteractivationtime(1蟛，higherconversionrate，lowerdem

8、andofsucrose(S0班)andhigherchiralproduction，comparedwi也Saccharomycescerevisiaeandbrewer’SyeastFurthermore，theappropriateconditionforthechiralintermediatepreparationbybaker’syeastwasatthetemperatureof29℃，sucrose80班，initial

9、pHof40，agitationof80r／rain，after40rainforcellactivation。addingethanol3％(v／v)andpanisaldehydeO08mol／Lfermemingfor14hrs，thecompositionofproductsWasgood，byproductofpMeO—BAwiththecontentof6370percent，whileP—MeO—PPDAreachingt

10、hecontentof27，76percent，andtheratiobetweenthetwO&scendedto2295。ThechiralproductPMeO—PPDA，iscolorlessneedlecrystals，yield1012％，whichwereconfirmedtobepMeOPPDAbyMS，IR鞏NuclearMagneticResonance(1HNMR)andothertestsHighpurityup

11、to95％，【僅]D24=一52o(cO005，CHCl3)，meltingpointof98℃，it幽esnotdissolveinwaterneitherinhexaneandmethan01butitCanbedissolvedinacetoacetateandchlorofornlKeywords：YeastSaccharomycescerevisiae，pAnisaldehyde，(一)(1R，zs)1一(4一Methoxyp