Van Ostrand Robert, Jacobsen Casey, Delahunty Alicia, Stringer Carley, Noorbehesht Ryan, Ahmed Haidi, Awad Ahmed M
a Chemistry Program, California State University Channel Islands , Camarillo , CA , USA.
Nucleosides Nucleotides Nucleic Acids. 2017 Mar 4;36(3):181-197. doi: 10.1080/15257770.2016.1250906. Epub 2017 Jan 3.
Reported is an efficient synthesis of adenyl and uridyl 5'-tetrachlorophthalimido-5'-deoxyribonucleosides, and guanylyl 5'-azido-5'-deoxyribonucleosides, which are useful in solid-phase synthesis of phosphoramidate and ribonucleic guanidine oligonucleotides. Replacement of 5'-hydroxyl with tetrachlorophthalimido group was performed via Mitsunobu reaction for adenosine and uridine. An alternative method was applied for guanosine which replaced the 5'-hydroxyl with an azido group. The resulting compounds were converted to 5'-amino-5'-deoxyribonucleosides for oligonucleotide synthesis. Synthetic intermediates were tested as antimicrobials against six bacterial strains. All analogs containing the 2',3'-O-isopropylidine protecting group demonstrated antibacterial activity against Neisseria meningitidis, and among those analogs with 5'-tetrachlorophthalimido and 5'-azido demonstrated increased antibacterial effect.
报道了一种高效合成腺苷基和尿苷基5'-四氯邻苯二甲酰亚胺-5'-脱氧核糖核苷以及鸟苷基5'-叠氮基-5'-脱氧核糖核苷的方法，这些核苷可用于磷酸酰胺和核糖胍寡核苷酸的固相合成。对于腺苷和尿苷，通过 Mitsunobu 反应将5'-羟基用四氯邻苯二甲酰亚胺基团取代。对于鸟苷则应用了另一种方法，即用叠氮基团取代5'-羟基。所得化合物被转化为5'-氨基-5'-脱氧核糖核苷用于寡核苷酸合成。合成中间体针对六种细菌菌株进行了抗菌测试。所有含有2',3'-O-异丙叉基保护基团的类似物均表现出对脑膜炎奈瑟菌的抗菌活性，并且在那些具有5'-四氯邻苯二甲酰亚胺和5'-叠氮基取代的类似物中显示出增强的抗菌效果。
