School of Chemistry, Analytical and Biological Chemistry Research Facility , University College Cork , Cork , Ireland.
Rega Institute for Medical Research , KU Leuven , B-3000 Leuven , Belgium.
J Org Chem. 2018 Sep 7;83(17):10510-10517. doi: 10.1021/acs.joc.8b01124. Epub 2018 Aug 22.
The synthesis of guanine α-carboxy nucleoside phosphonate (G-α-CNP) is described. Two routes provide access to racemic G-α-CNP 9, one via base construction and the other utilizing Tsuji-Trost allylic substitution. The latter methodology was also applied to the enantiopure synthesis of both antipodes of G-α-CNP, each of which showing interesting antiviral DNA polymerase activity. Additionally, we report an improved multigram scale preparation of the cyclopentene building block 10, starting material for the preferred Tsuji-Trost route to 9.
本文描述了鸟嘌呤α-羧基核苷膦酸（G-α-CNP）的合成。有两种方法可以得到外消旋的 G-α-CNP9，一种是通过碱基构建，另一种是利用 Tsuji-Trost 烯丙基取代。后一种方法也被应用于 G-α-CNP 的对映体纯的合成，每个对映体都表现出有趣的抗病毒 DNA 聚合酶活性。此外，我们还报告了改进的多克规模制备环戊烯砌块 10 的方法，这是 Tsuji-Trost 路线制备 9 的首选原料。
