Vongsutilers Vorasit, Daft Jonathan R, Shaughnessy Kevin H, Gannett Peter M
West Virginia University, Department of Basic Pharmaceutical Sciences, Morgantown, WV 26506, USA.
Molecules. 2009 Sep 2;14(9):3339-52. doi: 10.3390/molecules14093339.
A general scheme for the synthesis of C8-arylpurine phosphoramidites has been developed. C8-Arylation of C8-bromo-2'-deoxyguanosine is the key step and has been achieved through the use of a Suzuki coupling. Since the coupling reaction is conducted under aqueous conditions, it is unnecessary to protect and then deprotect the hydroxyl groups, thus saving several steps and improving overall yields. Once the C8-arylgroup is introduced, the glycosidic bond becomes very sensitive to acid catalyzed cleavage. Protection of the amino groups as the corresponding N,N-dimethylformamidine derivative improves stability of the derivatives. Synthetic C8-arylpurines were successfully used to prepare synthetic oligonucleotides.
已开发出一种合成C8-芳基嘌呤亚磷酰胺的通用方案。C8-溴-2'-脱氧鸟苷的C8-芳基化是关键步骤，已通过铃木耦合反应实现。由于耦合反应是在水性条件下进行的，因此无需保护然后脱保护羟基，从而节省了几个步骤并提高了总产率。一旦引入C8-芳基，糖苷键对酸催化的裂解就变得非常敏感。将氨基保护为相应的N,N-二甲基甲脒衍生物可提高衍生物的稳定性。合成的C8-芳基嘌呤已成功用于制备合成寡核苷酸。
