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摘要：特拉万星(telavancin)属于脂糖肽类化合物中的一种，是万古霉素的半合成衍生物。它做为一种快速杀菌的注射用抗生素，用于治疗耐药革兰阳性菌感染特别是甲氧西林耐药金葡菌(MRSA)感染。该药最初由Theravance公司研发，已于2009年通过美国FDA审批用于治疗革兰阳性菌包括MRSA引起的复杂性皮肤软组织感染(cSSTI)。而N-(9-芴甲氧羰基)-癸胺基乙醛作为特拉万星的一条侧链，是它的关键中间体。在特拉万星的合成过程中，第一步反应就是加上该侧链，该反应是特拉万星结构中的一个伯胺基官能团与该侧链的醛基发生还原胺化反应。虽然N-(9-芴甲氧羰基)-癸胺基乙醛的合成路线有多条，但成熟的工业化生产的路线只有一条，那就是以N-癸基氨基乙醇为原料，经过Fmoc-Cl 保护、斯文氧化等步骤制得该中间体。然而该路线存在产率较低，副产物较多等缺点，因此现在急需更好的合成路线。现就特拉万星及其侧链侧链N-(9-芴甲氧羰基)-癸胺基乙醛的作用机制、合成路线等进行综述。
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关键词：特拉万星 万古霉素 N-(9-芴甲氧羰基)-癸胺基乙醛 斯文氧化4197
The synthesis of Telavancin intermediate of N-(9-fluorenyl methoxy-carbonyl)-decyl-amino-acetaldehyde
Abstract: telavancin is one of lipoglycopeptide compounds , is a semi-synthetic derivative of vancomycin , It is for the treatment of resistant Gram -positive bacteria infections as a rapid bactericidal injectable antibiotic, especially methicillin-resistant Staphylococcus aureus ( MRSA ) infection. The drug was originally developed by Theravance, It has Approved by the U.S. FDA for the treatment of Gram-positive bacteria in 2009, including the complicated skin and soft tissue infections ( cSSTI ) caused by MRSA. N-(9- fluorenyl methoxy carbonyl)- decyl amine acetaldehyde is a key intermediate of telavancin as one of its side chain. In the synthesis process of telavancin, the first step reaction was coupled with the side chain，The reaction is that a primary amine functional group of telavancin structure react the reductive amination reaction with the aldehyde group of the side chain. Although there is a number of the Synthesis route of N-(9-fluorenyl methoxy carbonyl )-decyl amine acetaldehyde, But the mature industrialized production route is only one, that is made by N-decyl aminoethanol which is one of the primary material after the steps of Fmoc-Cl protection and Sven oxidation and so on. However, the route exists many shortcomings such as low yield and more byproducts, Hence there is a urgent need of a better synthetic route. Now we summarize the mechanism of action and the synthetic route that are in respect of the telavancin and its side chain N-(9-fluorenyl methoxy carbonyl)-the Kuei amino acetaldehyde mechanism, ect.
keyword: Telavancin vancomycin N-(9- fluorenyl methoxy carbonyl)- decyl amine acetaldehyde Sven oxidation
目录
1.绪论4
1.1细菌耐药性的产生及其发展概况 4
1.2 抗菌药物作用机制5
1.3 N-烷基化的介绍 6
1.3.1 N-烷基化剂常用类型6
1.4 氨基的保护8
1.4.1 有机合成中的氨基保护的方法8
1.4.1.1形成酰胺法8
1.4.1.2形成氨基甲酸酯和尿素型化合物的保护法9
1.4.1.3形成N2烷基衍生物的保护法9
1.4.1.4形成 C = N 键保护氨基10
1.4.1.5质子化反应和熬合反应对氨基的保护10
1.4.1.6用含磷有机物保护氨基10
1.4.2 常见的氨基保护基11
1.4.3 氨基保护基的选择策略11
1.4.4 各种烷氧羰基类氨基保护基的优劣分析11