{"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}
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.