Synthesis of 6-Aza-2-Hydroxyimino-5-Methylpyrimidine Nucleosides for Antiviral Evaluation.

Current Protocols Pub Date : 2021-12-01 DOI:10.1002/cpz1.329
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
{"title":"Synthesis of 6-Aza-2-Hydroxyimino-5-Methylpyrimidine Nucleosides for Antiviral Evaluation.","authors":"Reham A I Abou-Elkhair,&nbsp;Jinxi Du,&nbsp;Abdalla A Wasfy,&nbsp;Nisrin A Khaill,&nbsp;Hend M Maaroof,&nbsp;Marwa H Hassan,&nbsp;Ayman S Ahmed,&nbsp;Abdalla E A Hassan,&nbsp;Jia Sheng","doi":"10.1002/cpz1.329","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11174,"journal":{"name":"Current Protocols","volume":" ","pages":"e329"},"PeriodicalIF":0.0000,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Protocols","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/cpz1.329","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
自引率
0.00%
发文量
0
期刊最新文献
Using the Sleeping Beauty (SB) Transposon to Generate Stable Cells Producing Enveloped Virus-Like Particles (eVLPs) Pseudotyped with SARS-CoV-2 Proteins for Vaccination. Assessment of Antitumor and Antiproliferative Efficacy and Detection of Protein-Protein Interactions in Cancer Cells from 3D Tumor Spheroids. Genome Reporting for Healthy Populations-Pipeline for Genomic Screening from the GENCOV COVID-19 Study. "SIT" with Emx1-NuTRAP Mice: Simultaneous INTACT and TRAP for Paired Transcriptomic and Epigenetic Sequencing. Maize Seedling Growth and Hormone Response Assays Using the Rolled Towel Method.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1