【作者】 李小菊；

【导师】 石德清；

【作者基本信息】 华中师范大学 ， 有机化学， 2004， 硕士

【摘要】 5-氟尿嘧啶和替加氟[(1-四氢呋喃-2-基)-5-氟尿嘧啶]是目前临床使用的一类抗肿瘤药物。但由于其脂溶性小、选择性较差、毒副作用较大限制了它们的广泛应用。近些年来，许多化学家们对它们进行化学修饰，期望得到高效低毒的抗肿瘤前药。 为了寻找新型的5-氟尿嘧啶类药物，本文以替加氟为原料设计合成了20种未见文献报道的含磷(膦)酸酯的替加氟的衍生物。采用红外光谱，核磁共振氢谱、磷谱、质谱、元素分析对目标化合物的结构进行了表征，并对其物理化学性质、波谱性质、反应条件、合成方法及分离提纯等进行了系统的分析和探讨。目标化合物的结构式如下： (1)1-(四氢呋喃-2-基)-3-[4-(O，O-二烷基硫代磷酰基，S-亚甲基羰基氧代)烃基]-5-氟尿嘧啶 (2)1-(四氢呋喃-2-基)-3-(O，O-二烷基膦酰基烷氧羰基亚甲基)-5-氟尿嘧啶⑧硕士学位论文、IAST〔R’S一fHESIS }}(RO)，一p一干甲一OOCC R二Me，Et R’二ary一a!勺l 初步的生物活性测试结果表明，这两类目标化合物表现出一定程度的抑制肿瘤活性，同时，第二系列化合物还显示出较好的杀菌活性。更多还原

【Abstract】 5-Fluorouracil and Tegafur[l-(tetrahydrofiiran-2-yl)-5-fluorouracil] are both antitumor drugs which are widely used in clinic. However, their bad selectivitity and evident side effects limit their application. In recent years, many chemists have modified their chemical structures and hope to develop a better drug to overcome its shortcomings.In order to search novel 5-fluorouracil derivative antitumor drugs, we designed and synthesized 20 novel tegafur containing phosphorus compounds. Their structures were confirmed by IR, 1H NMR, 31P NMR, MS and elemental analysis. The properties of physical, chemical and spectroscopy of these compounds were systematically investigated. The reaction methods and reaction conditions were also investigated. The molecular formulas of the title compounds can be shown asfollows respectively.( I )1 -(tetrahydrofuran-2-yl)-3-[4-(O,O-dialkylthiophosphoryl,S-methylenecarbony-loxo)alkyl]-5-fluorouraciln=4, R=Me , Et, n-Pr, i-Pr, n-Bu , i-Bu. n=2, R=Et (II)1 -(tetrahydrofuran-2-yl)-3-(O,O-dialkylphosphono-alkoxylcarbonylmethylene)-5-fluorouracilThe results of preliminary bioassay show that the new compounds possess some extent of antitumor activities. Moreover, the second type of compounds exhibit good fungicidal activities. At the same time, it also provided basic experimental date about structure-activity relationship of these two kinds of compounds.更多还原