Cheek Marcus A, Dobrikov Mikhail I, Wennefors Charlotta K, Xu Zhihong, Hashmi Syed Nadeem, Shen Xiaoying, Shaw Barbara Ramsay
Department of Chemistry, Duke Universty, BOX 90346, Durham, NC 27708, USA.
Nucleic Acids Symp Ser (Oxf). 2008(52):81-2. doi: 10.1093/nass/nrn041.
The alpha-P-borano modification, where one of the alpha-phosphate oxygens is replaced by borane, of chain terminating nucleoside triphosphates are currently being tested in cell culture and are showing promise as effective viral polymerase inhibitors. The goal of this project is to combine the alpha-P-borano and Nanogel drug delivery technology to increase the antiviral potency of chain terminating sugar and base modified purine nucleosides versus the Hepatitis C Viral RNA dependent RNA polymerase (HCV RdRp). Here we show the synthesis of Cordycepin and 2'-O-methyl alpha-P-borano triphosphate via a one-pot phosphorochloridite synthesis under mild conditions. These analogues will be used for future structure-activity relationship (SAR) studies.
α-P-硼烷修饰是指链终止核苷三磷酸的一个α-磷酸氧原子被硼烷取代，目前正在细胞培养中进行测试，并显示出有望成为有效的病毒聚合酶抑制剂。该项目的目标是将α-P-硼烷和纳米凝胶药物递送技术相结合，以提高链终止糖和碱基修饰的嘌呤核苷对丙型肝炎病毒RNA依赖性RNA聚合酶（HCV RdRp）的抗病毒效力。在此，我们展示了在温和条件下通过一锅法亚磷酰氯合成法合成虫草素和2'-O-甲基α-P-硼烷三磷酸。这些类似物将用于未来的构效关系（SAR）研究。
