【作者】 张涛；

【导师】 方志杰；

【作者基本信息】 南京理工大学 ， 化学工程与技术， 2017， 博士

【摘要】 碳苷具有优异的化学和生物学稳定性,即耐酸碱性和对糖苷酶的稳定性,常常被作为一类非常重要的合成砌块,应用于碳苷类天然产物和药物的合成。本论文以β-葡萄糖碳苷为原料,合成一系列具有潜在应用前景的碳苷型化合物,并探索了其在表面活性剂、天然产物、荧光探针等领域的应用。其主要内容如下:1.分别采用酸、碱催化方法合成相应的呋喃型和吡喃型丙酮基-β-葡萄糖碳苷,并研究其反应条件。在酸催化葡萄糖与二苯甲酰基甲烷的反应中,得到了新化合物2-苯基-5-[(1R,2S,3S)-1,2,3,4-丁四醇基]-呋喃2.2。通过对催化剂、溶剂、反应温度的筛选,确定了合成化合物2.2的较佳反应条件;用NMR,HRMS对目标化合物的结构进行了解析。2.丙酮基-β-葡萄糖碳苷3.2上2,3位羟基的区域选择性反应及单晶解析。以葡萄糖为原料经两步合成糖碳苷底物3.2,总产率在58%。选择不同的酰化试剂,分析区域选择性反应结果趋向于3位取代产物的主要原因是:酰化试剂的吸电性越强,立体位阻效应越大,越易得到3位取代产物。此外,对其中3位取代产物3.4j进行了单晶结构解析,从微观上分析了碳苷的结构,并表明影响该晶体稳定性的因素为分子间氢键和边对面的π-π堆积作用。3.紫外响应的碳苷型糖脂类表面活性剂的合成与应用。从葡萄糖出发经三步反应合成该碳苷型糖脂。与传统的糖类表面活性剂相比,该糖脂类表面活性剂具有紫外响应的特性,可以通过液相色谱的紫外检测器直接检测,且从中间体到产物均可通过重结晶的方法得到,后处理操作更简单。4.根据药物设计的相似性原理和拼合原理,由呋喃型丙酮基-β-葡萄糖碳苷合成糖碳苷型查尔酮类化合物,并探索其抗氧化活性和细胞毒性。其中化合物5.2c具有优异的抗氧化能力(抑制率为63.55%)和对人体肝癌细胞和乳腺癌细胞具有一定的抗增殖活性,IC50值分别为4.9 μM和19 μM。此外,比较呋喃型糖碳苷和吡喃型糖碳苷的查尔酮类似物的抗氧化活性,结果表明:吡喃型碳苷的抗氧化活性较优。5.一种基于糖碳苷类水溶性荧光探针的合成与应用。对比含糖基荧光探针和不含糖基荧光探针的光谱特性,发现前者具有优异的水溶性和生物相容性,且其在水溶液中具有更高的荧光强度。用DFT密度泛函的方法,对合成出的八种化合物进行理论计算,说明探针体系的电子密度越大,共轭效应越强,越利于荧光的产生。由于该探针在极性质子溶液中荧光淬灭,在水溶液中可与蛋白质结合产生绿色荧光,其荧光强度与蛋白浓度成优异的线性关系,因此化合物6.1h可望用于制作蛋白检测的试剂盒。此外,还研究了探针6.1h在胰蛋白酶水解和细胞染色方面的作用。更多还原

【Abstract】 C-Glycosides have received increasing attention in recent years because of their preferable properties in biological functions and stability against acidic or enzymatic hydrolysis.They are often used as a kind of vital building block in the synthesis of natural products and medicines.In this thesis,we have reported the synthesis of new C-glycosides with potential applications in the field of surfactant,natural product and fluorescent probe.1.β-C-furanoside and β-C-pyranoside were synthesized respectively by acid and base catalyzation.Lewis acids catalyzing in the condensation of D-glucose and dibenzoylmethane to obtain(1R,2S,3S)-1-(5-phenylfuran-2-yl)butane-1,2,3,4-tetraol 2.2 has been reported.Experiments were carried out to determine the optimum conditions by varying the catalysts,solvents and temperatures.The structure of target compound was confirmed by NMR and HRMS.2.Selective mono-protection of diols in acetonyl-C-glucoside was studied.The esterification substrate 3.2 was synthesized over two steps in the total yield of 58%.Regioselective esterification resulted majorly into 3-substituted products.Results indicated that strong electron-withdrawing and large space steric hindrance of esterification reagents lead to regioselective substituted products.The X-ray diffraction analysis of 3-substitued product 3.4j was also researched.The factors leading to the stabilization of the crystal,including the edge-to-face π-π interaction and hydrogen bonds were discussed.3.The synthesis and application of UV-visible C-glycolipid surfactant were studied.The C-glycolipids were synthesized over three steps.Compared with traditional alkyl glycoside surfactants,these kind of surfactants are UV-visible and can be tested by HPLC ultraviolet detector.Besides,all these newly synthesized compounds can be separated by recrystallization,which is economical and cost effective.4.Synthesis of C-furanosyl chalcone analogues of aspalathin have been carried out based on the similarity and association principle of drug design.The antioxidant activities and the anticancer activities were studied.Compound 5.2c appeared to be the most promising compound with good antioxidant ability(inhibition%= 63.55%)and inhibition towards Hep-G2 and MCF-7 cells,IC50 at 4.9μM,19μM respectively.The antioxidant abilities of C-furanosides and C-pyranosides were compared and noted that the C-pyranosides are more active.5.Synthesis and application of a novel water soluble fluorescent probe based on C-glycoside were researched.The comparison between carbohydrate-derived probe and none-carbohydrate-derived probe indicated that neutral probe with carbohydrate moiety showed more excellent hydrophily,biocompatibility and higher fluorescent intensity in water solution.DFT methods was used to study these eight compounds,which suggested that high electron density and large conjugated degree of probes were benefit for the fluorescent properties.Fluorescent spectroscopic studies showed that the as-prepared dye could be used in the labeling of BSA as the fluorescence of this dye was quenched in water and turned on after incubated with protein.The fluorescent intensity and the concentration of protein are of an excellent linear relation which indicated that the probe 6.1h could be used in the development of protein assay kit.Besides,compound 6.1h was preliminarily studied in the field of monitoring trypsin hydrolysis and cell staining.更多还原