Abstract Synthesis of 1-((4 R,5S,6R,7R)-5,6-dihydroxy-7-(hydroxymethyl)spiro[2.4]heptan-4-yl)pyrimidine-2,4(1H,3H)-dione (12) and its phosphoramidate prodrug 18 is reported. The synthesis of the targeted compound 12 was initiated from triol 1. By the introduction of a substituent methylene group at 6-position of 4, followed by Simmons-Smith cyclopropanation and amination, key intermediate 10 was synthesized. The intermediate amine 10 was utilized to synthesize the nucleoside 12. Furthermore, the nucleoside 12 was derivatized to 2′-α-hydroxy-2′-β-methyl (23) and 2′-α-fluoro-2′-β-methyl (27) analogs. All synthesized derivatives of spiro-cyclopropyl carbocyclic uridine analogs 12, 18, 23 and 27 were evaluated for anti-HCV activity, but none of the compounds, reported in this article show any anti-HCV activity.

中文翻译：

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2'-脱氧-2'-氟-2'-C-甲基螺环戊基碳环尿苷类似物的合成作为HCV NS5B聚合酶的潜在抑制剂

摘要 1-((4 R,5S,6R,7R)-5,6-二羟基-7-(羟甲基)螺[2.4]庚烷-4-基)嘧啶-2,4(1H,3H)-二酮的合成(12)及其氨基磷酸酯前药18有报道。目标化合物12的合成从三醇1开始。通过在4的6位引入取代基亚甲基，然后进行Simmons-Smith环丙烷化和胺化，合成了关键中间体10。中间体胺10用于合成核苷12。此外，核苷12衍生为2'-α-羟基-2'-β-甲基（23）和2'-α-氟-2'-β-甲基(27) 类似物。对螺环丙基碳环尿苷类似物 12、18、23 和 27 的所有合成衍生物进行了抗 HCV 活性评估，但本文报道的所有化合物均未显示任何抗 HCV 活性。