Synthesis of Adenine Nucleosides with a Reactive (β-Iodovinyl)sulfone or (β-Keto)sulfone Group at the C2 Position and Their Polymerase-Catalyzed Incorporation into DNA.
A Hasan Howlader, Richard Fernandez, Pawlos S Tsegay, Yuan Liu, Stanislaw F Wnuk
{"title":"Synthesis of Adenine Nucleosides with a Reactive (<i>β</i>-Iodovinyl)sulfone or (<i>β</i>-Keto)sulfone Group at the C2 Position and Their Polymerase-Catalyzed Incorporation into DNA.","authors":"A Hasan Howlader, Richard Fernandez, Pawlos S Tsegay, Yuan Liu, Stanislaw F Wnuk","doi":"10.3390/molecules30061358","DOIUrl":null,"url":null,"abstract":"<p><p>Iodosulfonylation of an ethynyl group at the C2 position of 2'-deoxyadenosine or adenosine with TsI provides (<i>E</i>)-2-(<i>β</i>-iodovinyl)sulfones. The latter undergo nucleophilic substitution with amines via an addition-elimination to give <i>β</i>-sulfonylvinylamines (enamines). Acid-catalyzed hydrolysis of the <i>β</i>-sulfonylvinylamines provides 2-(<i>β</i>-keto)sulfones, mechanistically different probes that react with alkyl halides, resulting in α-alkylation. Adenine nucleosides with a β-ketosulfone group at C2, during conversion to their 5'-triphosphate form, undergo an unexpected conversion to 2-carboxylic acid nucleotides. The 5'-triphosphate of 2'-deoxyadenosine-2-carboxylic acid was incorporated by a human DNA polymerase into a one-nucleotide gap DNA substrate.</p>","PeriodicalId":19041,"journal":{"name":"Molecules","volume":"30 6","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944392/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecules","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.3390/molecules30061358","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Iodosulfonylation of an ethynyl group at the C2 position of 2'-deoxyadenosine or adenosine with TsI provides (E)-2-(β-iodovinyl)sulfones. The latter undergo nucleophilic substitution with amines via an addition-elimination to give β-sulfonylvinylamines (enamines). Acid-catalyzed hydrolysis of the β-sulfonylvinylamines provides 2-(β-keto)sulfones, mechanistically different probes that react with alkyl halides, resulting in α-alkylation. Adenine nucleosides with a β-ketosulfone group at C2, during conversion to their 5'-triphosphate form, undergo an unexpected conversion to 2-carboxylic acid nucleotides. The 5'-triphosphate of 2'-deoxyadenosine-2-carboxylic acid was incorporated by a human DNA polymerase into a one-nucleotide gap DNA substrate.
期刊介绍：
Molecules (ISSN 1420-3049, CODEN: MOLEFW) is an open access journal of synthetic organic chemistry and natural product chemistry. All articles are peer-reviewed and published continously upon acceptance. Molecules is published by MDPI, Basel, Switzerland. Our aim is to encourage chemists to publish as much as possible their experimental detail, particularly synthetic procedures and characterization information. There is no restriction on the length of the experimental section. In addition, availability of compound samples is published and considered as important information. Authors are encouraged to register or deposit their chemical samples through the non-profit international organization Molecular Diversity Preservation International (MDPI). Molecules has been launched in 1996 to preserve and exploit molecular diversity of both, chemical information and chemical substances.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
