{"title":"[利用 4'-碳自由基合成修饰核苷]。","authors":"Yuta Ito","doi":"10.1248/yakushi.24-00117","DOIUrl":null,"url":null,"abstract":"<p><p>Nucleosides with a substituent at the 4'-position have received much attention as antiviral drugs and as raw materials for oligonucleotide therapeutics. 4'-Modified nucleosides are generally synthesized using ionic reactions through the introduction of electrophilic or nucleophilic substituents at the 4'-position. However, their synthetic methods have some drawbacks; e.g., (i) it is difficult to control stereoselectivity at the 4'-position; (ii) complex protection-deprotection processes are required; (iii) the range of electrophiles and nucleophiles is limited. With this background, we considered that a carbon radical generated at the 4'-position would be a useful intermediate for the synthesis of 4'-modified nucleosides. In this review, two novel methods for the generation of 4'-carbon radicals are summarized. The first utilizes radical deformylation involving β-fragmentation of a hydroxymethyl group at the 4'-position. The other utilizes radical decarboxylation and 1,5-hydrogen atom transfer (1,5-HAT), which enables the generation of 4'-carbon radicals while retaining the hydroxymethyl group at the 4'-position. These methods enable the rapid and facile generation of 4'-carbon radicals and provide various 4'-modified nucleosides including 2',4'-bridged structures.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":"144 9","pages":"877-886"},"PeriodicalIF":0.3000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"[Synthesis of Modified Nucleosides Using 4'-Carbon Radicals].\",\"authors\":\"Yuta Ito\",\"doi\":\"10.1248/yakushi.24-00117\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Nucleosides with a substituent at the 4'-position have received much attention as antiviral drugs and as raw materials for oligonucleotide therapeutics. 4'-Modified nucleosides are generally synthesized using ionic reactions through the introduction of electrophilic or nucleophilic substituents at the 4'-position. However, their synthetic methods have some drawbacks; e.g., (i) it is difficult to control stereoselectivity at the 4'-position; (ii) complex protection-deprotection processes are required; (iii) the range of electrophiles and nucleophiles is limited. With this background, we considered that a carbon radical generated at the 4'-position would be a useful intermediate for the synthesis of 4'-modified nucleosides. In this review, two novel methods for the generation of 4'-carbon radicals are summarized. The first utilizes radical deformylation involving β-fragmentation of a hydroxymethyl group at the 4'-position. The other utilizes radical decarboxylation and 1,5-hydrogen atom transfer (1,5-HAT), which enables the generation of 4'-carbon radicals while retaining the hydroxymethyl group at the 4'-position. These methods enable the rapid and facile generation of 4'-carbon radicals and provide various 4'-modified nucleosides including 2',4'-bridged structures.</p>\",\"PeriodicalId\":23810,\"journal\":{\"name\":\"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan\",\"volume\":\"144 9\",\"pages\":\"877-886\"},\"PeriodicalIF\":0.3000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1248/yakushi.24-00117\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1248/yakushi.24-00117","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
[Synthesis of Modified Nucleosides Using 4'-Carbon Radicals].
Nucleosides with a substituent at the 4'-position have received much attention as antiviral drugs and as raw materials for oligonucleotide therapeutics. 4'-Modified nucleosides are generally synthesized using ionic reactions through the introduction of electrophilic or nucleophilic substituents at the 4'-position. However, their synthetic methods have some drawbacks; e.g., (i) it is difficult to control stereoselectivity at the 4'-position; (ii) complex protection-deprotection processes are required; (iii) the range of electrophiles and nucleophiles is limited. With this background, we considered that a carbon radical generated at the 4'-position would be a useful intermediate for the synthesis of 4'-modified nucleosides. In this review, two novel methods for the generation of 4'-carbon radicals are summarized. The first utilizes radical deformylation involving β-fragmentation of a hydroxymethyl group at the 4'-position. The other utilizes radical decarboxylation and 1,5-hydrogen atom transfer (1,5-HAT), which enables the generation of 4'-carbon radicals while retaining the hydroxymethyl group at the 4'-position. These methods enable the rapid and facile generation of 4'-carbon radicals and provide various 4'-modified nucleosides including 2',4'-bridged structures.