Bamford M J, Coe P L, Walker R T
School of Chemistry, University of Birmingham, Edgbaston, England.
J Med Chem. 1990 Sep;33(9):2488-94. doi: 10.1021/jm00171a024.
The synthesis and antiviral activity of a number of 3'-C-difluoromethyl and 3'-deoxy-3'-C-fluoromethyl nucleosides are reported. The 3'-C-difluoromethyl nucleosides 26a and 26b were obtained by treatment of the corresponding 2',5'-di-O-protected-3'-C-formyl nucleosides 25a and 25b with (diethylamino)sulfur trifluoride (DAST). Removal of the 2'-O-protecting group from 26a and subsequent reaction with DAST furnished the 2'-deoxy-2'-fluoro-beta-D-ribo-pentofuranosyl nucleoside 29. Selective fluorination with DAST of the 5'-O-protected analogues 3'-deoxy-3'-C-hydroxymethyl derivatives 13a and 13b gave the 3'-deoxy-3'-C-fluoromethyl derivatives 30a and 30b, while nonselective fluorination afforded the 2',3'-dideoxy-2'-fluoro-3'-C-fluoromethyl analogues 31a and 31b. The deprotected uracil analogue 17a was iodinated to the 5-iodouracil derivative 18. The fully deprotected fluorinated 3'-C-branched nucleosides 14-18 and 32 were evaluated for their antiviral activity. None were active against human immunodeficiency virus type-1 (HIV-1) at concentrations up to 100 microM. However, 5-iodouracil analogue 18 showed activity, comparable to that of acyclovir, against varicella zoster virus without observed cytotoxicity.
报道了多种3'-C-二氟甲基和3'-脱氧-3'-C-氟甲基核苷的合成及其抗病毒活性。3'-C-二氟甲基核苷26a和26b是通过用（二乙氨基）三氟化硫（DAST）处理相应的2',5'-二-O-保护的3'-C-甲酰基核苷25a和25b得到的。从26a中除去2'-O-保护基并随后与DAST反应得到2'-脱氧-2'-氟-β-D-核糖戊呋喃糖基核苷29。用DAST对5'-O-保护的类似物3'-脱氧-3'-C-羟甲基衍生物13a和13b进行选择性氟化得到3'-脱氧-3'-C-氟甲基衍生物30a和30b，而非选择性氟化得到2',3'-二脱氧-2'-氟-3'-C-氟甲基类似物31a和31b。脱保护的尿嘧啶类似物17a被碘化得到5-碘尿嘧啶衍生物18。对完全脱保护的氟化3'-C-支链核苷14 - 18和32的抗病毒活性进行了评估。在浓度高达100 microM时，没有一种对1型人类免疫缺陷病毒（HIV-1）有活性。然而，5-碘尿嘧啶类似物18对水痘带状疱疹病毒显示出与阿昔洛韦相当的活性，且未观察到细胞毒性。
