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题目：手性基因靶向药物聚酰胺的构建及其关键二聚体合成工艺条件的优化 摘要：目前，寡聚酰胺（PAS）的合成主要采取两种方法：液相合成法和固相合成法。本文旨在针对寡聚酰胺（PAS）在液相法合成中,出现合成产率低,路线长，操作繁琐等问题，对构建寡聚酰胺所需的关键片断进行研究和工艺方面的改进。采取片断偶合的策略,探索出了一条方法简便、路线简短、高效、高产、绿色环保的合成路线。通过以N-甲基吡咯、N-甲基咪唑作为起始原料，经过F-C酰基化反应、硝化、卤仿反应、还原、水解、Fmoc-氨基保护等反应步骤设计并合成出4个关键二聚体（dimer）片段，并且对市场现有的单体合成工艺进行了改进和优化，简化了其合成步骤，缩短了合成时间，极大的提高了其产率和纯度；为后续手工固相合成吡咯-咪唑聚酰胺提供了必要的原料。文章还设计了由(S)--羟基--氨基丁酸作为手性识别元素，所合成的关键二聚体片段（dimer）作为基本构建元素，通过手工固相合成的方法构建了 2条具有手性修饰的吡咯-咪唑聚酰胺。此法克服了手工固相合成过程中富电子的杂环酸与缺电子的亲核咪唑胺的偶联困难问题，节约试剂的同时提高了产量与固相合成的效率和收率，减少了对环境的污染。为今后进一步研究聚酰胺在细胞分子生物学、动物模型中应用的研究，直至开发成新一代的靶向基因药物打下基础。 |
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moneyhost: 金币+10, 翻译EPI+1, ★有帮助 2013-04-09 19:24:59
phu_grassman: 金币+1, 翻译EPI-1, 杜绝机器翻译。 2013-04-14 09:15:10
moneyhost: 金币+10, 翻译EPI+1, ★有帮助 2013-04-09 19:24:59
phu_grassman: 金币+1, 翻译EPI-1, 杜绝机器翻译。 2013-04-14 09:15:10
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Optimization of the synthesis conditions of the chiral genetically targeted drugs polyamide build their critical dimer Abstract: Currently, the synthesis of polyamides (PAS), mainly taken two ways: the liquid phase synthesis and solid phase synthesis. This article aims to research and technology improvements in the liquid phase synthesis, polyamides (PAS), a synthetic low yield and long routes, complicated operation, building the key pieces required for polyamides. Take the fragment coupling the strategy to explore a method is simple, short routes, efficient, high-yield, green synthetic route. By N-methyl pyrrole, N-methyl imidazole as a starting material, after the acylation reaction to FC, nitration, haloform reaction, reduction, hydrolysis, Fmoc-amino protection reaction step was designed and synthesized four key dimerized body (dimer) fragments and monomer synthesis technology available on the market to improve and optimize, simplify the synthetic steps, shortening the synthesis time, greatly improving the yield and purity; solid-phase synthesis for subsequent manual pyrrole - imidazole polyamide provides the necessary raw materials. Article also by the (S) - - hydroxy - - amino butyric acid as a the chiral recognition element, the synthesized key dimer fragment (dimer) is designed as a basic building element, by manual solid-phase synthesis method of building 2 the strip has a chiral pyrrole - imidazole polyamide modified. This method overcomes the manual solid phase synthesis Cheng Zhongfu electronic heterocyclic acid and the nucleophilic imidazole amine coupling of electron-deficient difficult problem, while saving agents to improve the yield and efficiency of solid-phase synthesis and yield, and to reduce the environmental contamination. For further research polyamide research in cell and molecular biology, animal models of applications in the future, until the development to lay the foundation for a new generation of targeted gene drugs. |
11楼2013-03-15 15:24:55
2楼2013-03-12 22:08:23
hookhans
铁杆木虫 (著名写手)
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