奎宁类单季铵盐催化aza-Michael环化反应:合成Letermovir的有效途径

Liang Chen, Weiyuan Liu, Siju Bi, Ting Zhou, Jingwen Pan, Xunlei Lv, Kuaile Lin, Wei-cheng Zhou
{"title":"奎宁类单季铵盐催化aza-Michael环化反应:合成Letermovir的有效途径","authors":"Liang Chen, Weiyuan Liu, Siju Bi, Ting Zhou, Jingwen Pan, Xunlei Lv, Kuaile Lin, Wei-cheng Zhou","doi":"10.1055/s-0041-1740944","DOIUrl":null,"url":null,"abstract":"A series of mono- or bis-quaternary ammonium salts derived from cinchonidine or quinine was synthesized and screened as potent phase-transfer catalysts for the reaction of aza-Michael cyclization, the key step in the synthesis of letermovir. During the reaction of aza-Michael cyclization, the screened monoquaternary ammonium salt quinine derivative Q1 transferred 7 to 8 with 91.9% yield and 58% ee. The application of Q1 was preferred, due to its enantioselectivity, the possibility of reuse, and the lower cost in large-scale preparation. Furthermore, the racemization condition of letermovir enantiomer was also explored for the possibility to develop the resolution/racemization process. With the optimal catalyst Q1 in hand, the synthesis of letermovir may be more convenient and economical in the future.","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"20 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Enantioselective aza-Michael Cyclization Reaction Catalyzed by Quinine-Derived Monoquaternary Ammonium Salts: an Effective Route to Synthesize Letermovir\",\"authors\":\"Liang Chen, Weiyuan Liu, Siju Bi, Ting Zhou, Jingwen Pan, Xunlei Lv, Kuaile Lin, Wei-cheng Zhou\",\"doi\":\"10.1055/s-0041-1740944\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"A series of mono- or bis-quaternary ammonium salts derived from cinchonidine or quinine was synthesized and screened as potent phase-transfer catalysts for the reaction of aza-Michael cyclization, the key step in the synthesis of letermovir. During the reaction of aza-Michael cyclization, the screened monoquaternary ammonium salt quinine derivative Q1 transferred 7 to 8 with 91.9% yield and 58% ee. The application of Q1 was preferred, due to its enantioselectivity, the possibility of reuse, and the lower cost in large-scale preparation. Furthermore, the racemization condition of letermovir enantiomer was also explored for the possibility to develop the resolution/racemization process. With the optimal catalyst Q1 in hand, the synthesis of letermovir may be more convenient and economical in the future.\",\"PeriodicalId\":19767,\"journal\":{\"name\":\"Pharmaceutical Fronts\",\"volume\":\"20 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2021-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmaceutical Fronts\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1055/s-0041-1740944\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Fronts","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1055/s-0041-1740944","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

合成了一系列由cinchonidine或quinine衍生的单季铵盐或双季铵盐,并筛选了它们作为合成letermovir的关键步骤za- michael环化反应的有效相转移催化剂。在aza-Michael环化反应中,筛选出的单季铵盐奎宁衍生物Q1转移7 ~ 8,产率91.9%,ee 58%。由于Q1具有对映体选择性,可重复使用,且大规模制备成本较低,因此首选应用Q1。此外,还对左旋对映体的外消旋条件进行了探讨,以期开发拆分/外消旋工艺。有了最佳催化剂Q1,未来合成letermovir可能会更加方便和经济。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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
Enantioselective aza-Michael Cyclization Reaction Catalyzed by Quinine-Derived Monoquaternary Ammonium Salts: an Effective Route to Synthesize Letermovir
A series of mono- or bis-quaternary ammonium salts derived from cinchonidine or quinine was synthesized and screened as potent phase-transfer catalysts for the reaction of aza-Michael cyclization, the key step in the synthesis of letermovir. During the reaction of aza-Michael cyclization, the screened monoquaternary ammonium salt quinine derivative Q1 transferred 7 to 8 with 91.9% yield and 58% ee. The application of Q1 was preferred, due to its enantioselectivity, the possibility of reuse, and the lower cost in large-scale preparation. Furthermore, the racemization condition of letermovir enantiomer was also explored for the possibility to develop the resolution/racemization process. With the optimal catalyst Q1 in hand, the synthesis of letermovir may be more convenient and economical in the future.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
24
审稿时长
15 weeks
期刊最新文献
Recent Advances in Mitochondrial Pyruvate Carrier Inhibitors Discovery of a Novel Benzimidazole Necroptosis Inhibitor from an In-House Compound Library Research Strategies for Precise Manipulation of Micro/Nanoparticle Drug Delivery Systems Using Microfluidic Technology: A Review Advances in Tumor Targeting Biomimetic Drug Delivery Systems: A Promising Approach for Antitumor Therapy 3D Printing Pharmaceuticals: Current Status and Future Opportunities
×
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