新型n-烷基取代3,4-二氢嘧啶酮-c60的合成分析-synthesis and analysis of new n - alkyl substituted 3,4 - dihydropyrimidinone - c60.docx

摘 要C60 因其独特的结构以及在抗菌、抗 HIV 病毒、DNA 裂解、抗肿瘤以及酶活 性抑制等方面具有的独特功效和生物活性而受到广泛关注。C60 对生物酶具有较强 的 π-π 堆积作用，能够与生物靶酶分子结合，表现出很好的生物活性，这在抗菌 药物中有着重要的作用。3,4-二氢嘧啶-2-酮（DHPM）化合物是一种具有杂环结构 和药理学特性的化合物，不仅能通过阻止脱氧嘧啶核苷的合成和互换，对 DNA 的 合成进行干扰,而且还具有抗菌、抗病毒、抗高血压等生物活性。研究发现，被 N 功能化的 DHPM 化合物会表现出更加好的药学活性。N-烷基化的 DHPM 化合物通 过与 DNA 发生烷基化作用，也会对 DNA 的合成产生影响。我们通过药物设计有 效的方法把各亚单元进行叠加，合成新型的 N1-烷基取代 DHPM-C60 衍生物，并对 其光学性质和生物活性进行研究，以期得到具有更高生物利用度的化合物，这对 新型药物的开发具有重要意义。本论文主要研究内容如下：第一，通过 Biginelli 反应合成系列 DHPM 衍生物， 并对其生物活性进行研究，筛选出具有较高抗菌活性的化合物。第二，设计合成 23 个 N1-烷基取代 DHPM 化合物。第三，设计合成 25 个中间产物。第四，设计 合成 25 个新型 N-烷基取代 DHPM-C60 吡咯烷化合物，研究其光学性质和生物活性， 以期得到具有较高抗菌活性的新型化合物。目标产物及中间产物，利用 1H NMR、 13C NMR、HSQC、HMBC、HR-MS、IR、UV-vis 进行表征，确认其结构。关键词：C60; 3,4-二氢嘧啶-2-酮；抗菌; BiginelliiABSTRACTFullerene has been paid more attention for its special structure and the promising biological activities, such as antibacterial, anti -HIV virus, DNA-cleaning, antitumor and inhibition of enzyme activity. It is important in antibacterial that C60 has strong π-π interaction and can be combined with biological target molecules, which exhibits excellent biological activities. 3,4-dihydropyrimidine-2-(1H)-ones are a kind of compounds with heterocyclic structure and pharmacological properties, which not only interfere the synthesis of DNA by blocking the synthesis and exchange of deoxidation of pyrimidine nucleoside, but also has antibacterial, antihypertension activities, and so on. As studies show that N-functional DHPM usually have more excellent pharmacological activities. N-alkyl-DHPM compounds also have an impact on the synthesis of DNA through alkylation with DNA. With the method of drug design to superimposed subunits, we synthesize novel N1-alkylated-DHPM-C60 derivatives, and study the optical properties and biological activities in order to obtain the compounds with higher bioavailability, which has important significance for the development of the new drug.The main research contents are as follows. Firstly, synthesized a series of DHPM derivatives