磷酸西他列汀的合成路线设计摘要：第一个能够对Ⅱ型糖尿病中的二肽基肽酶-Ⅳ（DPP-4）起到治疗作用的抑制剂药物是磷酸西他列汀，它是由默克公司进行研究发现的。本药品可以控制血糖，再加以控制饮食和运动效果更佳。本文通过分析对比国内外有关磷酸西他列汀的资料，查找其的合成步骤，并而且以文献的案例为参考，以2,4,5-三氟苯乙酸和以2,4,5-三氟苄溴为起始原料两种方法，探索设计出一条以2,4,5-三氟苯乙酸作为起跑点，然后把3-氧代-4-（2,4,5-三氟苯基）丁酸乙酯当做中间点，使得它们二者产生反应，从而制造出磷酸西他列汀，这是一条新的磷酸西他列汀生产路线，为磷酸西他列汀的生产应用提供参考。关键词：磷酸西他列汀；合成；2,4,5-三氟苯乙酸；2,4,5-三氟苄溴SyntheticroutedesignofSitagliptinphosphatemonohydrateAbstract：Sisalectinphosphate,developedbyMerck,isthefirstdrugoftheclassofdipeptidylpeptidase-IV(DPP-4)inhibitorsforthetreatmentoftype2diabetes.Thismedicinecancontrolbloodsugar,andthencontroldietandexercisebetter.Thispaperanalyzesandcomparesthesynthesismethodsofsitagliptinphosphateindomesticandforeignliteratures,andreferences2,4,5-trifluorophenylaceticacidand2,4,5-trifluorobenzylbromideintheliterature.Twomethodsofrawmaterials,andexploredthedesignofanintermediateof2-oxo-4-(2,4,5-trifluorophenyl)butanoatewith2,4,5-trifluorophenylaceticacidasthestartingmaterial.Anewrouteforthesynthesisofsitagliptinphosphateprovidesareferencefortheproductionofsitagliptinphosphate.Keywords:sitagliptinphosphate;synthesis;2,4,5-trifluorophenylaceticacid;2,4,5-trifluorobenzylbromide目录1绪论.....................................................................................................................................11.1抗糖尿病药物的研究进展.......................................................................................12磷酸西他列汀的概述..........................................................................................................12.1结构与性质.......................................................................................................12.2磷酸西他列汀的药理作用...............................................................................23磷酸西他列汀合成的方法..................................................................................................33.1以2,4,5-三氟苯乙酸为起始原料.............................................................................33.1.1合成路线一....................................................................................................33.1.2合成方法二....................................................................................................43.1.3合成方法三....................................................................................................53.2.4合成方法四....................................................................................................63.2以2,4,5-三氟苄溴为起始原料.................................................................................73.2.1合成方法........................................................................................................74磷酸西他列汀的合成路线设计..........................................................................................94.1合成路线设计的原则...............................................................................................94.2合成路线设计路线...................................................................................................94.2.1中间体...
