氟代碳环核苷：2'-和6'-氟代碳环嘧啶核苷的合成及抗病毒活性，包括碳环1-(2-脱氧-2-氟-β-D-阿拉伯呋喃糖基)-5-甲基尿嘧啶和碳环1-(2-脱氧-2-氟-β-D-阿拉伯呋喃糖基)-5-碘尿嘧啶。

Fluoro carbocyclic nucleosides: synthesis and antiviral activity of 2'- and 6'-fluoro carbocyclic pyrimidine nucleosides including carbocyclic 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-methyluracil and carbocyclic 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil.

作者信息

Borthwick A D, Evans D N, Kirk B E, Biggadike K, Exall A M, Youds P, Roberts S M, Knight D J, Coates J A

机构信息

Department of Microbiological Chemistry, Glaxo Group Research, Greenford, Middlesex, U.K.

出版信息

J Med Chem. 1990 Jan;33(1):179-86. doi: 10.1021/jm00163a030.

DOI:10.1021/jm00163a030

PMID:2153201

Abstract

The racemic carbocyclic 2'-fluoroarabinosyl pyrimidine nucleosides 8, 9 (C-FIAU), 12, and 13 (C-FMAU) and the 2'-fluororibosyl pyrimidine nucleosides 17, 20, and 21 were prepared from their respective protected 2'-fluoro amino diols 5 and 14. The carbocyclic 2'-2'-difluorothymidine analogue 27 was obtained from the protected difluoro amino diol 24 which was prepared from the ketone 23 and (diethylamino)sulfur trifluoride (DAST). The chiral carbocyclic 2'-deoxy-6'-fluorouridines 33, 34, 38, and 39 were synthesized from the protected 6'-fluoro amino diols 30 and 36, which were prepared by reduction of the azides 28 and 35. C-FMAU (13) and C-FIAU (9) were active in vitro against HSV-1 with ID50 values of 4.4 and 11 micrograms/mL, respectively, but they were inactive against HSV-2. The cytidine analogues 12 and 20 displayed modest activity in vitro against HSV-1 and HSV-2 but were inactive against human influenza A virus.

摘要

外消旋碳环2'-氟阿拉伯糖基嘧啶核苷8、9（C-FIAU）、12和13（C-FMAU）以及2'-氟核糖基嘧啶核苷17、20和21是由它们各自的受保护的2'-氟氨基二醇5和14制备而成。碳环2'-2'-二氟胸苷类似物27是从受保护的二氟氨基二醇24获得的，该二氟氨基二醇24是由酮23和三氟甲磺酸二乙胺基酯（DAST）制备的。手性碳环2'-脱氧-6'-氟尿苷33、34、38和39是由受保护的6'-氟氨基二醇30和36合成的，而这些受保护的6'-氟氨基二醇30和36是通过叠氮化物28和35的还原制备的。C-FMAU（13）和C-FIAU（9）在体外对单纯疱疹病毒1型（HSV-1）具有活性，ID50值分别为4.4和11微克/毫升，但它们对单纯疱疹病毒2型（HSV-2）无活性。胞苷类似物12和20在体外对HSV-1和HSV-2表现出适度活性，但对甲型人流感病毒无活性。