Departament de Química, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
Laboratory of Virology and Chemotherapy, Rega Institute, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium.
Int J Mol Sci. 2022 Aug 26;23(17):9704. doi: 10.3390/ijms23179704.
The enantioselective preparation of the two isomers of 4-hydroxy-2-cyclohexanone derivatives , was achieved, starting from a common cyclohexenone, through asymmetric transfer hydrogenation (ATH) reactions using bifunctional ruthenium catalysts. From these versatile intermediates, a stereoselective route to a cytosine analogue built on a bicyclo [4.1.0]heptane scaffold is described. Nucleoside kinase activity assays with this cyclopropyl-fused cyclohexane nucleoside, together with other related nucleosides (-), were performed, showing that thymine- and guanine- containing compounds have affinity for herpes simplex virus Type 1 (HSV-1) thymidine kinase (TK) but not for human cytosolic TK-1, thus pointing to their selectivity for herpetic TKs but not cellular TKs.
通过使用双功能钌催化剂进行不对称转移氢化（ATH）反应，从一种常见的环己烯酮出发，实现了两种 4-羟基-2-环己酮衍生物对映异构体的对映选择性制备。从这些多功能中间体出发，描述了一种基于双环[4.1.0]庚烷支架的胞嘧啶类似物的立体选择性合成路线。对该环丙基稠合环己烷核苷及其它相关核苷（-）进行了核苷激酶活性测定，结果表明胸腺嘧啶和鸟嘌呤化合物对单纯疱疹病毒 1 型（HSV-1）胸苷激酶（TK）具有亲和力，但对人细胞质 TK-1 没有亲和力，因此它们对疱疹 TK 的选择性而不是对细胞 TK 的选择性。
