Di Xie, Jiwei Tang, Tingting Zhang, Wenpei Dong, Tao Jiang, Jinliang Ma* and Chang-Po Chen*,
{"title":"双分子同步大环化策略合成核苷间胍键环二核苷酸类似物","authors":"Di Xie, Jiwei Tang, Tingting Zhang, Wenpei Dong, Tao Jiang, Jinliang Ma* and Chang-Po Chen*, ","doi":"10.1021/acs.joc.5c01753","DOIUrl":null,"url":null,"abstract":"<p >Internucleoside guanidinium linkages are excellent mimics of phosphodiesters and have been used to improve the properties of oligonucleotides. Herein we reported a step economic bimolecular simultaneous macrocyclization (BSM) protocol to prepare cyclic dinucleotide (CDN) analogues with guanidinium linkages. Compared with the 26 steps protocol reported in literature, the current method could provide CDN analogues with internucleoside guanidinium linkages in 9 steps, and the key intermediate prepared in the first 3 steps could be shared to prepare CDN analogues with different nucleobases. The CDN analogues were investigated as STING agonist in mammalian cells, and biofilm inhibitor in Gram-positive and Gram-negative bacteria. Compound <b>13c</b> showed the best biofilm inhibition in <i>Escherichia coli</i>, with the inhibition rate of 54% at the concentration of 78 μM.</p>","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"90 37","pages":"13145–13155"},"PeriodicalIF":3.6000,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A Bimolecular Simultaneous Macrocyclization Strategy to Synthesize Cyclic Dinucleotide Analogues with Internucleoside Guanidinium Linkages\",\"authors\":\"Di Xie, Jiwei Tang, Tingting Zhang, Wenpei Dong, Tao Jiang, Jinliang Ma* and Chang-Po Chen*, \",\"doi\":\"10.1021/acs.joc.5c01753\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Internucleoside guanidinium linkages are excellent mimics of phosphodiesters and have been used to improve the properties of oligonucleotides. Herein we reported a step economic bimolecular simultaneous macrocyclization (BSM) protocol to prepare cyclic dinucleotide (CDN) analogues with guanidinium linkages. Compared with the 26 steps protocol reported in literature, the current method could provide CDN analogues with internucleoside guanidinium linkages in 9 steps, and the key intermediate prepared in the first 3 steps could be shared to prepare CDN analogues with different nucleobases. The CDN analogues were investigated as STING agonist in mammalian cells, and biofilm inhibitor in Gram-positive and Gram-negative bacteria. Compound <b>13c</b> showed the best biofilm inhibition in <i>Escherichia coli</i>, with the inhibition rate of 54% at the concentration of 78 μM.</p>\",\"PeriodicalId\":57,\"journal\":{\"name\":\"Journal of Organic Chemistry\",\"volume\":\"90 37\",\"pages\":\"13145–13155\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-09-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Organic Chemistry\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.joc.5c01753\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Organic Chemistry","FirstCategoryId":"1","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.joc.5c01753","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
A Bimolecular Simultaneous Macrocyclization Strategy to Synthesize Cyclic Dinucleotide Analogues with Internucleoside Guanidinium Linkages
Internucleoside guanidinium linkages are excellent mimics of phosphodiesters and have been used to improve the properties of oligonucleotides. Herein we reported a step economic bimolecular simultaneous macrocyclization (BSM) protocol to prepare cyclic dinucleotide (CDN) analogues with guanidinium linkages. Compared with the 26 steps protocol reported in literature, the current method could provide CDN analogues with internucleoside guanidinium linkages in 9 steps, and the key intermediate prepared in the first 3 steps could be shared to prepare CDN analogues with different nucleobases. The CDN analogues were investigated as STING agonist in mammalian cells, and biofilm inhibitor in Gram-positive and Gram-negative bacteria. Compound 13c showed the best biofilm inhibition in Escherichia coli, with the inhibition rate of 54% at the concentration of 78 μM.
期刊介绍：
Journal of Organic Chemistry welcomes original contributions of fundamental research in all branches of the theory and practice of organic chemistry. In selecting manuscripts for publication, the editors place emphasis on the quality and novelty of the work, as well as the breadth of interest to the organic chemistry community.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
