β-d-2'-脱氧-2'-α-氯-2'-β-氟和β-d-2'-脱氧-2'-α-溴-2'-β-氟核苷及其膦酰胺前药的合成及抗 HCV 活性。
Synthesis and anti-HCV activity of β-d-2'-deoxy-2'-α-chloro-2'-β-fluoro and β-d-2'-deoxy-2'-α-bromo-2'-β-fluoro nucleosides and their phosphoramidate prodrugs.
机构信息
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
出版信息
Bioorg Med Chem. 2019 Feb 15;27(4):664-676. doi: 10.1016/j.bmc.2019.01.005. Epub 2019 Jan 9.
Abstract
We report herein the synthesis and evaluation of a series of β-d-2'-deoxy-2'-α-chloro-2'-β-fluoro and β-d-2'-deoxy-2'-α-bromo-2'-β-fluoro nucleosides along with their corresponding phosphoramidate prodrugs. Key intermediates, lactols 11 and 12, were obtained by a diastereoselective fluorination of protected 2-deoxy-2-chloro/bromo-ribonolactones 7 and 8. All synthesized nucleosides and prodrugs were evaluated with a hepatitis C virus (HCV) subgenomic replicon system.
摘要
我们在此报告了一系列β-d-2'-脱氧-2'-α-氯-2'-β-氟和β-d-2'-脱氧-2'-α-溴-2'-β-氟核苷及其相应的磷酰胺酯前药的合成和评价。关键中间体，内酯 11 和 12，通过保护的 2-脱氧-2-氯/溴-核糖内酰胺 7 和 8 的非对映选择性氟化得到。所有合成的核苷和前药均通过丙型肝炎病毒（HCV）亚基因组复制子系统进行了评估。
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