摘要：在所有的新型的噁唑烷酮类抗生素中，利奈唑胺为第一个应用于临床的。并且已经在临床疗效方面得到了很多的研究证明，其中包括：抑制蛋白的起始复合物的减少细菌蛋白质的合成，还有在体内以及体外对于葡萄球菌种、链球菌种、肠球菌种等等耐药G+茵等具有很好的抗菌的作用。三氟甲基的引入能改变母体化合物的活性，在医药方面有很多应用。因此，本论文拟以利奈唑胺为先导化合物，将三氟甲基引入到噁唑烷酮结构中，以期得到含三氟甲基的利奈唑胺衍生物，并进行杀菌活性筛选。在本论文中我们以三氟甲基烷氧乙烯基酮为原料与芳基肼反应合成得到含5-三氟甲基-吡唑环结构，并用该结构替换噁唑烷酮类代表药物利奈唑胺中的吗啉环，保持右边基团不变，合成一个含5-三氟甲基-吡唑环的新型噁唑烷酮类化合物。在这个过程中，用1H-NMR来验证最为关键的中间体，用1H-NMR，13C-NMR，19F-NMR和HRMS最后的目标产物结构。29734
毕业论文关键词：利奈唑胺；噁唑烷酮类抗菌药；三氟甲基
Synthesis of New Oxazolidinone Compounds Containing 5- three Fluorine Methyl Pyrazole Ring
Abstract: Linezolid is a new oxazolidinone antibiotic first used in clinical, formation by inhibiting protein initiation complex to inhibit bacterial protein synthesis, in vivo, antibacterial effect on Staphylococcus aureus, Streptococcus broad-spectrum resistant bacteria, Enterococcus G+, its clinical curative effect has been proved a series of clinical research. The introduction of the three methyl fluoride can change the activity of the parent compound, has many applications in medicine. Therefore, this thesis intends to linezolid as lead compound, three methyl fluoride into oxazolidinone structures, linezolid derivatives containing three methyl fluoride was in order, and bactericidal activity screening. In this paper we take three trifluoromethyl alkyl vinyl ketone as raw material and aryl hydrazine was synthesized with 5- three fluorine methyl pyrazole ring structure, and the structure to replace the morpholine ring oxazolidinone linezolid in representative drugs, stay to the right group invariant, new oxazolidinone synthesis of a 5- containing three fluorine methyl pyrazole ring. Among them, the key intermediates were verified by 1H-NMR and the target compounds was verified by all NMR and HRMS spectrum.
Key Words: Linezolid ;oxazolidinoneantibacterials; Trifluoromethyl
目录
1 前言 5
1.1抗菌药物的简介 5
1.1.1 抗菌药研究现状 6
1.1.2各类合成抗菌药和作用机制 7
1.2噁唑烷酮类化合物 9
1.2.1噁唑烷酮类化合物的简介 9
1.2.2噁唑烷酮类化合物的作用机制 9
1.3利奈唑胺 10
1.3.1利奈唑胺的简介 10
1.3.2利奈唑胺的作用机制 10
1.3.3利奈唑胺的体内药动学 11
1.4含三氟甲基化合物 11
1.4.1含三氟甲基化合物的简介 11
1.4.2 含三氟甲基的代表性化合物 11
2 文献综述与方案论证 13
2.1噁唑烷酮类化合物的构效关系 13
2.2 文献综述 14
2.3 方案论证 16
2.4 确定实验路线 16
3 实验部分 17
3.1 试剂及仪器 17
3.1.1 试剂 17
3.1.2 仪器 18
3.2实验方法 19
4 结果与讨论 22
4.1混合溶液过柱时产生气泡的原因和解决方法 22
4.2萃取中产生乳化现象 22 新型的含氟的噁唑烷酮类药物中间体的制备:http://www.youerw.com/yixue/lunwen_25093.html