| 一种HCV抑制剂中间体9-羟基-6-氧-4-甲基菲啶的全合成 |
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| 作者单位： | ;1.云南大学化学科学与工程学院;2.南京农业大学动物医学院;3.中国科学院昆明植物研究所植物化学与西部植物资源持续利用国家重点实验室;4.云南中医学院中药学院 |
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| 摘 要： | 石蒜碱具有明显的抗丙肝病毒感染HCV(hepatitis C virus,HCV)活性,在对石蒜碱衍生物进行抗HCV活性研究时发现其中菲啶类化合物普遍具有比较良好的抗HCV活性,由于此类化合物活性优良,毒性较低,因此有必要对其进行深入的结构修饰与构效关系研究.对菲啶类衍生物重要合成中间体9-羟基-6-氧-4-甲基菲啶进行了全合成,该方法以2-溴-5-甲氧基苯甲酸为原料,包括酰胺化、偶联反应、以及脱甲基等3步,其中钯催化芳基-芳基,N-芳基一步偶联为该合成方法关键步骤,该方法步骤简便,原料简单易得,收率较高(总收率54%)可以为后续研究提供稳定的化合物来源.
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| 关 键 词： | 全合成 9-羟基-6-氧-4-甲基菲啶 钯催化烷基-烷基 N-芳基一步偶联 |
Total synthesis of 9-hydroxy-6-oxo-4-methylphenanthridine for a HCV-inhibiting intermediate |
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| Affiliation: | ,School of Chemical Science and Engineering,Yunnan University,College of Veterinary Medicine,Nanjing Agricultural University,State Key Laboratory of Phytochemistry and Plant Resources in West China,Kunming Institute of Botany,Chinese Academy of Sciences,School of Traditional Chinese Medicine,Yunnan University of Traditional Chinese Medicine |
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| Abstract: | The previous studies reveal that galanthidine has obvious anti- HCV activities. The phenanthridine compounds as the derivative of galanthidine have good anti- HCV activities and low toxicity,which deserves further studies. This research focuses on a three- step synthesis of 9- hydroxy- 6- oxo- 4- methylphenanthridine,as the key intermediate of a series of potent HCV inhibitors. This synthesis features a consecutive aryl- aryl and N- aryl coupling,leading to 9- methyl- 6- oxo- 4- methylphenanthridine,whose structure is determined by the spectroscopic analysis and X- ray crystallography,in a one- pot aryl- aryl and N- aryl coupling sequence with the presence of palladium catalyst and the usage of TFP( Tri( 2- furyl) phosphine) as the ligand. For higher yields,the conditions of the key reaction are studied and optimized with an overall yield of 54%. |
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| Keywords: | total synthesis 9-hydroxy-6-oxo-4-methylphenanthridine palladium-catalyzed one-pot aryl-aryl N-aryl coupling |
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