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三类松香基杂环衍生物的合成及其性能研究

Synthesis of Three Series of Rosinyl Derivatives Containing Heterocycle and Study on the Products’ Property

【作者】 张业

【导师】 王恒山; 潘英明;

【作者基本信息】 广西师范大学 , 有机化学, 2007, 硕士

【摘要】 脱氢松香酸和脱氢松香胺是可再生资源松香异构体的重要成分,广泛应用于涂料、胶粘剂、油墨、造纸、橡胶、食品添加剂及生物制品、药物等领域。它们是手性纯物质,含有三个手性碳原子;具有反应性官能团——苯环、羧基和胺基;拥有许多天然药物都具有的芳香型三环二萜结构。因此,利用这些结构特点,在脱氢松香骨架上的反应性官能团上进行改造,有望合成出多功能脱氢松香衍生物,开发新型手性荧光试剂、高效低毒药物等具有高附加值的产品,带来良好的社会效益与经济效益。基于以上考虑,本文开展了脱氢松香的杂环化改造研究。(一)论文以脱氢松香酸为反应底物,经甲酯化、溴代、硝化、成环等步骤,合成了5个新型脱氢松香酸甲酯呋咱的衍生物;产物的λex在280-330 nm之间,λem在316-436 nm之间,与脱氢松香酸甲酯相比,它们的激发波长与发射波长分别红移35-70/16-36 nm;热稳定性研究表明,松香基呋咱衍生物的失重温度约为170℃,表现出较好的热稳定性;抗癌活性试验表明,12-溴-13, 14-氧化呋咱-脱异丙基脱氢松香酸甲酯、7-羰基-12, 13-呋咱-脱异丙基脱氢松香酸甲酯对MDA-MB-231的抑制率分别为61%和31.6%,有望开发成为新型松香类抗癌先导化合物。(二)以脱氢松香胺为起始反应物,通过与1, 8-萘酐母体缩合,然后再经过结构修饰得到12个新型N-松香基-4-取代-1, 8-萘酰亚胺衍生物;化合物的λex在390-490 nm之间,λem在400-570 nm之间,与脱氢松香酸甲酯相比,它们的激发波长与发射波长分别红移140-240/100-270 nm;对阴离子Cl-、Br-、I-识别试验表明,N-松香基-4-取代-1, 8-萘酰亚胺衍生物对Br-的识别能力最强,对Cl-的识别次之,对I-几乎没有识别能力,由此推出,其分子孔穴与Br-半径相近,约为0.114 nm;由于其良好的结构刚性,通过与DNApbr322作用,N-松香基-4-取代-1, 8-萘酰亚胺衍生物表现出优良的切割DNA分子的能力。(三)论文还通过13-氨基-脱异丙基脱氢松香酸甲酯与甘油脱水缩合,在松香骨架上构建了喹啉环,得到了两个喹啉衍生物;通过12-胺基-脱氢松香酸甲酯的重氮化反应,合成了一个12-Cl-脱氢松香酸甲酯中间体,单晶衍射结果与核磁共振分析结果吻合;松香基喹啉的荧光λexem=260-265/370-380 nm。(四)在优化N-松香基-1, 8-萘酰亚胺衍生物的合成条件的过程中,研究并开发了微波辐射下水溶剂法一步合成N-取代和N-, 4-,双取代-1, 8-萘酰亚胺的新方法,该方法反应条件温和,合成效率高,反应用时大大缩短,操作简单。总之,本论文共合成了30个新化合物,它们的结构用红外光谱、核磁共振谱、质谱等分析手段进行了鉴定。研究表明,通过在脱氢松香骨架上构建、设计芳杂环,脱氢松香的荧光性质、抗癌活性和切割DNA等性能得到明显改善,这为多功能脱氢松香产品的开发奠定了基础。

【Abstract】 Dehydroabietic acid (DAA) and dehydroabietylamine (DA) are the isomerides of the renewable rosin. They are widely used in the fields of paint, adhesives, printing ink, papermaking, rubber food and drugs, etc. Similar with many natural drugs, there are aromatic-diterpene-three-ring, three chiral carbon atoms and three reactive groups, benzene, carboxyl and amine on their skeleton. Therefore, DAA and DA might be hopefully modified to some multifunctional derivatives, which can be used as high added value products like novel fluorescence derivatization reagents and efficient but low toxic medicines, through constructing aromatic or heteroaromatic ring on the skeleton. It would bring about favorable economical and social effects. Therefore, we start to do the work of building the heterocycle ring on the rosinyl skeleton.(i) In this paper, firstly, from dehydroabietic acid, five novel furazan derivatives were synthesized with fluorescentλex/λem of 280-330/316-436 nm, through five steps, such as esterification, bromination, nitration, and so on. Compared with DAA’s methyl ester, the products’maximal excited wavelengths and emission wavelengths were bathochromic red shifted for 35-70/16-36 nm, respectively. The products were tested to be friendly stable with high temperature, and they began to lose the weight at the temperature 170℃. Besides, methyl 12-bromo-13, 14-oxofurazan-deisopropyl-dehydroabietate and methyl 7-oxo-12, 13-furazan-deisopropyl-dehydroabietate effectively inhibitted MDA-MB-231 in 61 and 31.6 percent, respectively, thus they were potential to be exploited for the precursor compounds of anti-cancer.(ii) Then, we obtained a series of N-rosinyl-4-substituted-1, 8-naphthalimides with fluorescentλexem of 390-490/400-570 nm, using DA as the precursor. In contrast with DAA’s methyl ester, their maximal excited wavelengths and emission wavelengths were red shifted for 140-240/100-270 nm. In our study, N-rosinyl-4-amino-1, 8-naphthalimides showed the best capability for detecting Br- anion, better capability for Cl- anion and no capability for I- anion, indicating that the cavity of these compounds was equal to the radius of Br- anion, says 0.114 nm. In our investigation, the products also displayed good incision property to DNA-pbr322, and they were considered to be novel ronyl drugs.(iii) By coupled with glycol, methyl 13-aminodeisopropyldehydroabietate was converted to two quinolines with fluorescentλexem of 260-265/370-380 nm. Treated with the complex of hydrochloric acid/natrium nitrite and then sodium acetate, methyl 12-amino-dehydroabietate was converted to methyl 12-chloro-dehydroabietate. Its structure was determined by 1H NMR, as well as the single crystal X-ray diffraction method. Both results showed the same structure.(iiii) In addition, in the optimization of reaction condition of N-rosinyl-1, 8-naphthalimides, a water-solvent-routed preparation of a series of N- and N-, 4- substituted 1, 8-naphthalimides under microwave irradiation, that proceeded via efficient and green reaction of 1, 8-naphthalic anhydride derivatives with different amines, was explored. In this method, the reaction completed in mild conditions, required only a few minutes of reaction time, afforded good yields, and the operation was very simple.In summary, in this paper, 30 new compounds were synthesized and characterized by IR, NMR, X-ray diffraction and MS etc. Our study showed that the properties of DAA and DA, such as fluorescence, thermostability can be improved through constructing aromatic or heteroaromatic ring on their skeleton. All that laid the groundwork for further exploitation of multifunctional reagents.

【关键词】 松香呋咱萘酰亚胺喹啉性能
【Key words】 RosinFurazansNaphthalimidesQuinolinesProperties
  • 【分类号】TQ351.471
  • 【被引频次】2
  • 【下载频次】355
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