葡萄糖拟螺核苷的合成
发布时间：2018-10-12 07:26
【摘要】：本篇论文首先对核苷类药物以及核苷类化合物的结构修饰进行了综述，然后以D-葡萄糖为原料进行了拟螺核苷的合成研究，利用Wittig反应、Michael加成反应、Mannich反应和Henry反应等，立体选择性的合成一系列的葡萄糖拟螺核苷类似物，本文所取得进展情况如下： 一、以D-葡萄糖为原料，经过两步反应得到氧化糖1，然后通过Wittig反应，Michael加成反应得到化合物3，最后通过对化合物3的Mannich反应得到葡萄糖拟螺核苷化合物4，5，6，7，8，9，10。其中6和7，8和9分别是立体异构体。 (a)干燥的CH3COCH3,浓H2SO4;(b) PDC, DCM, Ac2O;(c) Wittig试剂, CHCl3;(d) CH3NO2,DBU;(e) HCHO, C2H5OH, R-NH2 二、以D-葡萄糖为原料，经过四步反应得到饱和硝基化合物11，之后通过上Ts保护其中的6位羟基。(a)干燥的CH3COCH3,浓H2SO4;(b) PDC, DCM, Ac2O;(c) CH3NO2, THF, KF;(d) CH3OH,H2O,冰乙酸;(e) TsCl, Py 三、以D-葡萄糖为原料，，经多步反应得到不饱和硝基化合物13，然后通过Michael加成反应得到化合物14，最后通过羟基脱保护、上Ts得到化合物16。 (a) DMSO, Ac2O;(b) CH3NO2,无水THF, NaH;(c) CH3OH, H2O,冰乙酸;(d) TsCl, Py 在本论文中，共合成了18种化合物，其中13个化合物是新化合物，通过1H NMR，13C NMR，HR-MS，IR等分析方法对新化合物进行了结构表征。
[Abstract]:In this paper, the structure modification of nucleoside drugs and nucleoside compounds was reviewed, and then the synthesis of spiroside from D- glucose was studied. Wittig reaction, Michael addition reaction, Mannich reaction and Henry reaction were used. The progress of stereoselective synthesis of a series of glucospironoside analogues is as follows: first, using D-glucose as raw material, After two steps of reaction, sugar oxide 1 was obtained, then compound 3 was obtained by Wittig reaction and Michael addition reaction. Finally, the glucospironoside compound 4H5, 6, 7, 7, 8, 10 was obtained by the Mannich reaction of compound 3. Of these, 6 and 7, 8 and 9 were CH3COCH3, concentrated H _ 2SO _ 4 dried by stereoisomer. (a), respectively, and (b) PDC, DCM, Ac2O; (c) Wittig reagent, CHCl3; (d) CH3NO2,DBU; (e) HCHO, C _ 2H _ 5OH, R-NH2 _ 2, were used as raw materials for D- glucose. After four steps of reaction, saturated nitrocompound 11 was obtained, and then the 6 hydroxyl. (a) dried CH3COCH3, concentrated H _ 2SO _ 4 was protected by Ts, and (b) PDC, DCM, Ac2O; (c) CH3NO2, THF, KF; (d) CH3OH,H2O, acetic acid; (e) TsCl, Py _ 3 was used as raw material for D- glucose. The unsaturated nitro compound 13 was obtained by multistep reaction, then compound 14 was obtained by Michael addition reaction. Finally, the compound was protected by hydroxyl deprotection. (a) DMSO, Ac2O; (b) CH3NO2, anhydrous THF, NaH; (c) CH3OH, H 2O and acetic acid; (d) TsCl, Py in this thesis, 18 compounds were synthesized, 13 of which were new compounds. The structure of the new compound was characterized by 1H NMR,13C NMR,HR-MS,IR et al.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5
本文编号：2265283
[Abstract]:In this paper, the structure modification of nucleoside drugs and nucleoside compounds was reviewed, and then the synthesis of spiroside from D- glucose was studied. Wittig reaction, Michael addition reaction, Mannich reaction and Henry reaction were used. The progress of stereoselective synthesis of a series of glucospironoside analogues is as follows: first, using D-glucose as raw material, After two steps of reaction, sugar oxide 1 was obtained, then compound 3 was obtained by Wittig reaction and Michael addition reaction. Finally, the glucospironoside compound 4H5, 6, 7, 7, 8, 10 was obtained by the Mannich reaction of compound 3. Of these, 6 and 7, 8 and 9 were CH3COCH3, concentrated H _ 2SO _ 4 dried by stereoisomer. (a), respectively, and (b) PDC, DCM, Ac2O; (c) Wittig reagent, CHCl3; (d) CH3NO2,DBU; (e) HCHO, C _ 2H _ 5OH, R-NH2 _ 2, were used as raw materials for D- glucose. After four steps of reaction, saturated nitrocompound 11 was obtained, and then the 6 hydroxyl. (a) dried CH3COCH3, concentrated H _ 2SO _ 4 was protected by Ts, and (b) PDC, DCM, Ac2O; (c) CH3NO2, THF, KF; (d) CH3OH,H2O, acetic acid; (e) TsCl, Py _ 3 was used as raw material for D- glucose. The unsaturated nitro compound 13 was obtained by multistep reaction, then compound 14 was obtained by Michael addition reaction. Finally, the compound was protected by hydroxyl deprotection. (a) DMSO, Ac2O; (b) CH3NO2, anhydrous THF, NaH; (c) CH3OH, H 2O and acetic acid; (d) TsCl, Py in this thesis, 18 compounds were synthesized, 13 of which were new compounds. The structure of the new compound was characterized by 1H NMR,13C NMR,HR-MS,IR et al.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5
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本文编号：2265283
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