Kim Seyeon, Kim Eunae, Hong Joon Hee
a BK21 Project Team, College of Pharmacy , Chosun University , Kwangju , Republic of Korea.
Nucleosides Nucleotides Nucleic Acids. 2015;34(2):79-91. doi: 10.1080/15257770.2014.960977.
Novel 4 'α-trifluoromethyl-2 'β-methyl carbocyclic nucleoside analogs have been prepared and evaluated for inhibition of hepatitis C virus (HCV) RNA replication in cell cultures. Construction of cyclopentene intermediate 10a was achieved via sequential Johnson-Claisen orthoester rearrangement and ring-closing metathesis starting from the α-trifluoromethyl-α,β-unsaturated ester 5. Stereoselective dihydroxylation and desilylation yielded the target carbodine analogs. The synthesized nucleoside analogs mentioned above (18 and 19) were assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon Huh7 cell line (LucNeo#2). However, the synthesized nucleosides showed neither significant antiviral activity nor toxicity up to 50 μM.
已制备新型4'α-三氟甲基-2'β-甲基碳环核苷类似物，并在细胞培养中评估其对丙型肝炎病毒（HCV）RNA复制的抑制作用。环戊烯中间体10a的构建是通过从α-三氟甲基-α,β-不饱和酯5开始的连续约翰逊-克莱森原酸酯重排和闭环复分解反应实现的。立体选择性二羟基化和去硅基化反应生成了目标卡波定类似物。对上述合成的核苷类似物（18和19）在亚基因组复制子Huh7细胞系（LucNeo#2）中抑制HCV RNA复制的能力进行了测定。然而，合成的核苷在高达50μM的浓度下既没有显示出显著的抗病毒活性，也没有毒性。
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