Synthesis of 6-Aza-2-Hydroxyimino-5-Methylpyrimidine Nucleosides for Antiviral Evaluation.
Reham A I Abou-Elkhair, Jinxi Du, Abdalla A Wasfy, Nisrin A Khaill, Hend M Maaroof, Marwa H Hassan, Ayman S Ahmed, Abdalla E A Hassan, Jia Sheng
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引用次数: 1
Abstract
The syntheses of a series of novel 6-aza-2-hydroxyimino-5-methylpyrimidine and related nucleosides are described. A suitably protected 2-methylthiopyrimidine nucleoside was selected as the precursor for installing a hydroxyimino moiety at the C-2 position. The starting nucleobase 6-aza-5-methyl-2-thiouracil is prepared in two steps from thiosemicarbazone and ethyl pyruvate. This is subjected to coupling with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose under Vorbrüggen glycosylation conditions to provide the corresponding nucleoside in high yield. Activation of the nucleoside to the corresponding 2-methylthio derivative followed by treatment with hydroxylamine hydrochloride in pyridine provides the corresponding 2-hydroxyimino derivative in high yield. Finally, the synthesis of five free modified nucleoside analogs is described. The newly synthesized nucleosides have been evaluated against an RNA viral panel and moderate activity was observed against hepatitis C virus, Zika virus, and human respiratory syncytial virus. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Preparation of 6-aza-5-methyl-2-thiouracil Basic Protocol 2: Preparation of 6-aza-5-methyl-2-thiouridine and 6-aza-5-methyluridine Basic Protocol 3: Preparation of 6-aza-2-hydroxyimino-5-methyluridine Basic Protocol 4: Preparation of 6-aza-2-hydroxyimino-5-methyl-4-thiouridine and 6-aza-2-hydroxyimino-5-methylcytosine.
6-叠氮-2-羟亚胺-5-甲基嘧啶核苷的合成及其抗病毒评价
报道了一系列新型6-叠氮-2-羟基亚胺-5-甲基嘧啶及其相关核苷的合成。选择一个适当保护的2-甲基硫代嘧啶核苷作为在C-2位置安装羟基亚胺片段的前体。起始核碱基6-氮杂-5-甲基-2-硫脲嘧啶由硫代氨基脲和丙酮酸乙酯两步合成。在vorbr根糖基化条件下,与1- o -乙酰基-2,3,5-三- o -苯甲酰-β- d -核糖呋喃糖偶联,以高产出相应的核苷。将核苷活化为相应的2-甲基硫代衍生物,然后在吡啶中用盐酸羟胺处理,得到相应的高产2-羟亚胺衍生物。最后,介绍了五种游离修饰核苷类似物的合成。新合成的核苷已对RNA病毒面板进行了评估,并观察到对丙型肝炎病毒、寨卡病毒和人呼吸道合胞病毒有中等活性。©2021 Wiley期刊有限责任公司基本方案1:6-叠氮-5-甲基-2-硫脲嘧啶的制备基本方案2:6-叠氮-5-甲基-2-硫脲嘧啶和6-叠氮-5-甲基尿嘧啶的制备基本方案3:6-叠氮-2-羟基亚胺-5-甲基尿嘧啶的制备基本方案4:6-叠氮-2-羟基亚胺-5-甲基尿嘧啶的制备。
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