Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924, Łódź, Poland.
Chemistry. 2019 Oct 17;25(58):13309-13317. doi: 10.1002/chem.201902411. Epub 2019 Aug 22.
The synthesis of the protected form of 2-methylthio-N -threonylcarbamoyl adenosine (ms t A) was developed starting from adenosine or guanosine by using the optimized carbamate method and, for the first time, an isocyanate route. The hypermodified nucleoside was subsequently transformed into the protected ms t A-phosphoramidite monomer and used in a large-scale synthesis of the precursor 17nt ms t A-oligonucleotide (the anticodon stem and loop fragment of tRNA from T. brucei). Finally, stereochemically secure ms t A→ms ct A cyclization at the oligonucleotide level efficiently afforded a tRNA fragment bearing the ms ct A unit. The applied post-synthetic approach provides two sequentially homologous ms t A- and ms ct A-oligonucleotides that are suitable for further comparative structure-activity relationship studies.
保护形式的 2-甲基巯基-N-苏氨酰氨基甲酰腺苷（ms t A）的合成是从腺苷或鸟苷开始，通过优化的氨基甲酸酯法和首次采用异氰酸酯路线开发的。随后，将超修饰核苷转化为保护的 ms t A-磷酰胺单体，并用于大规模合成前体 17nt ms t A-寡核苷酸（来自 T. brucei 的 tRNA 的反密码子茎环片段）。最后，在寡核苷酸水平上通过立体化学稳定的 ms t A→ms ct A 环化有效地提供了带有 ms ct A 单元的 tRNA 片段。所应用的合成后方法提供了两个顺序同源的 ms t A-和 ms ct A-寡核苷酸，它们适合进一步进行结构-活性关系研究。
