2',3'-C-二甲基碳环核苷类似物作为潜在抗丙型肝炎病毒药物的合成及体外活性评价
Synthesis and in vitro activity evaluation of 2',3'-C-dimethyl carbocyclic nucleoside analogues as potential anti-HCV agents.
作者信息
Ko Ok Hyun, Hong Joon Hee
机构信息
BK21-Project Team, College of Pharmacy, Chosun University, Kwangju, Republic of Korea.
出版信息
Nucleosides Nucleotides Nucleic Acids. 2009 Aug;28(8):761-71. doi: 10.1080/15257770903155642.
The first synthetic route of novel 2'(beta),3'(beta)-C-dimethyl carbodine analogues is described. The key intermediate cyclopentenyl alcohol 11(beta) prepared from Weinreb amide 4 via ring-closing metathesis (RCM) and vicinal dihydroxylation. Coupling of 12 with nucleosidic bases via the Pd(0) catalyzed reaction followed by stereoselective dihydoxylation and deprotection afforded the target carbocyclic nucleoside analogues. The synthesized compounds were evaluated as inhibitors of the hepatitis C virus (HCV) in Huh-7 cell line in vitro. However, the nucleosides failed to inhibit HCV RNA replication in the cell-based replicon assay (EC(50) > microM).
描述了新型2'(β),3'(β)-C-二甲基卡波定类似物的第一条合成路线。关键中间体环戊烯醇11(β)由Weinreb酰胺4通过闭环复分解反应（RCM）和邻位二羟基化反应制备。12与核苷碱基通过钯(0)催化反应偶联，随后进行立体选择性二羟基化和脱保护反应，得到目标碳环核苷类似物。在体外Huh-7细胞系中对合成的化合物进行了丙型肝炎病毒（HCV）抑制剂的评估。然而，这些核苷在基于细胞的复制子试验中未能抑制HCV RNA复制（半数有效浓度>微摩尔）。
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