【作者】 张志广；

【导师】 渠桂荣；

【作者基本信息】 河南师范大学 ， 有机化学， 2007， 硕士

【摘要】 抗菌、抗病毒及抗肿瘤药物的研究是当今药物化学中的热点课题。本文致力于微波辐射下无环核苷、8-溴腺苷衍生物和5-碘尿嘧啶衍生物的设计与绿色合成。改进原有的合成方法,在微波辐射下,首次把水引入无环及卤原子取代的核苷类化合物的合成中,取得了一些方法学上的创新性结果。微波辐射下在水溶液中,通过核苷碱基与α,β不饱和亚甲基化合物的Michael addition反应,以较高的产率和区域选择性得到了60个无环核苷化合物,其中27个为新化合物;微波辐射下在水和DMF溶液中,通过亲核取代反应合成了33个另一类无环核苷化合物(肽核酸的前体),其中16个为新化合物;微波辐射下在水溶液溶液中合成了6个8-溴腺苷衍生物;微波辐射下在水溶液中合成了6个5-碘尿嘧啶衍生物。完成了这些化合物的合成、分离、谱图解析及结构表征等工作,所有的目标化合物的结构均经IR、1H-NMR、13C-NMR、MS和/或元素分析所确证。为了确认烷基化的位置,部分化合物还通过HMQC和HMBC谱确认。系统研究了核苷目标物的微波合成方法,优化了反应条件,实现了这一类化合物简便、高效和绿色的合成。在水体系中核苷类化合物能通过微波方法快速的合成,初步证明了本课题绿色合成核苷的设计思想具有一定的合理性。为今后深入进行其他绿色体系如离子液体、超临界二氧化碳中核苷类化合物的合成研究提供了重要的借鉴。本论文打通了水体系中对核苷类化合物用微波方法快速合成的绿色通道,具有较好的学术意义和实用价值。更多还原

【Abstract】 Recently, the research on the antibacterial, antiviral and antitumor drugs is a hot topic in the pharmaceutical chemistry. In this paper, we have devoted our efforts to design and prepare acyclic nucleosides, 8-bromo adenosine derivatives and 5-iodo uracil derivatives. It is the first time that we introduce water as the solvent to synthesize acyclic and halo atom substituted nucleosides with the help of microwave irradiation and several innovative results have been obtained.60 acyclic nucleoside derivatives were achieved in high yields and good regioselectivity, under microwave irradiation via Michael addition of various nucleobases toα,β-unsaturated methylene compounds, using water as the solvent and TEA as the base, 27 of which are new ones. Another 33 acyclic nucleosides, which can be used as important building blocks for peptide nucleic acids (PNAs), were obtained in water and DMF through the nucleophilic substitution of various nucleobases with chloroacetate, assisted by microwave irradiation, of which 16 compounds have not been reported in literatures. Six 8-bromo adenosine derivatives and six 5-iodo uracil derivatives were finished in aqueous system within short reaction times. Their structures were confirmed by IR, 1H-NMR, 13C-NMR, MS and/or elemental analysis, and some of them were further ascertained by HMQC and HMBC spectra in order to assert the site of alkylation. We have systemically studied the methodology of microwave-promoted the preparation of nucleosides, obtained the optimal reaction conditions, and realized the rapid and green synthesis of this kinds of compounds.In this paper, a number of nucleoside derivatives were synthesized under microwave irradiation using water as the green solvent, which testified that our design on the green synthesis of nucleosides is rational, which presents an important model for the preparation of these kinds of compounds in other environmental-friendly systems, such as room temperature ionic liquids, super-critical CO2. In summary, we get through the green route of microwave-assisted the rapid syntheses of nucleosides and their derivatives in water and these results have good value in learning and application.更多还原