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摘要：随着抗生素的大量使用甚至是滥用，使细菌的耐药性问题口益严重。噁唑烷酮类抗菌药物是八十年代逐步发展起来的一类新型的全合成抗生素。该类药物在化学结构上均有一噁唑烷二酮母核，具有全新的抗菌机制，对革兰阳性球菌，特别是多重耐药的革兰阳性球菌，具有较强的抗菌活性, 且与其他抗菌药物无交叉耐药现象，在药用领域应用广泛，代表药物是利奈唑胺。
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本论文针对利奈唑胺类衍生物进行修饰，保留利奈唑胺右边的基团，引入含三氟甲基的吡唑取代吗啉环，以期获得一个含三氟甲基的新的噁唑烷酮类化合物。在有机化合物中引入氟原子可以极大的改变化合物的物理化学性质及在生物体内的生理活性。因而在杂环化合物中引入氟原子的研究引起了国内外化学工作者的广泛兴趣。本论文主要是设计和合成了一个重要的关键中间体：4-(5-(三氟甲基)-1H-吡唑-1-基)苯胺，首先通过三氟乙酸酐和不同的烯醚反应得到烷氧乙烯基三氟甲基酮砌块。再利用该砌块与对硝基苯肼反应合成得到吡唑环，最后用钯碳还原得到含三氟甲基的吡唑取代的苯胺产物，此化合物是合成目标产物的重要中间体。9478
本研究关键中间体和最终目标产物的结构经1H-NMR确认。关键词：利奈唑胺；新型抗菌药噁唑烷酮类合成；三氟甲基
Synthesis of aniline derivatives containing the trifluoromethyl group substituted pyrazolo
Abstract: With the extensive use of antibiotics or even abused, so that bacterial resistance problem Kuchimasu serious. Oxazolidinone antibacterial drugs eighties gradually developed a new class of synthetic antibiotics. In the chemical structure of these drugs have an oxazolidinone nucleus, with a new antibacterial mechanism against Gram-positive bacteria, especially multidrug-resistant Gram-positive cocci, with a strong antibacterial activity, and with other no cross-resistance to antimicrobial drugs phenomenon, widely used in the pharmaceutical field, on behalf of the drug is linezolid.
In this thesis, linezolid modified amine derivatives retain the right linezolid group, including the introduction of trifluoromethyl pyrazole substituted morpholine ring, in order to obtain a new trifluoromethyl-containing oxazolidinone compounds. Introducing a fluorine atom in the organic compound can greatly change the physical and chemical properties of the compound in vivo and physiological activity. Thus the introduction of fluorine atoms in the heterocyclic compound of chemical workers at home and abroad has aroused widespread interest. In this thesis, the design and synthesis of an important key intermediate: 4 - (5 - (trifluoromethyl)-1H-pyrazol-1 - yl) aniline, first by trifluoroacetic anhydride and allyl ether of the type obtained Alkoxyvinyl trifluoromethyl ketone blocks. Re-use of the block with p-nitrophenyl hydrazine synthesized pyrazole ring, the final reduction with palladium on carbon (trifluoromethyl) pyrazole-containing substituted aniline product, this compound is an important intermediate for synthesis of the desired product.
Chemical structure of Linezolid and its intermediates has been confirmed by 1H-NMR．
Key words: Linezolid；New antibacterial drugs Synthesis of the oxazolidinone class of drugs； Trifluoromethyl
目录
1 前言1
1.1 抗菌药物的简介1
1.2 噁唑烷酮类化合物1
1.2.1噁唑烷酮类化合物的概况1
1.2.2噁唑烷酮类药物的意义2
1.2.3噁唑烷酮类化合物的作用机制3
1.3 利奈唑胺3
1.3.1 利奈唑胺概述3
1.3.2 利奈唑胺的作用机制4
1.4 含氟化合物4
2 文献综述与方案论证 6
2.1 文献综述 6
2.1.1 结构修饰6
2.1.2 利奈唑胺的合成方法7