A new synthesis and an antiviral assessment of the 4'-fluoro derivative of 4'-deoxy-5'-noraristeromycin.
A new synthesis and an antiviral assessment of the 4'-fluoro derivative of 4'-deoxy-5'-noraristeromycin.
复制标题
4-脱氧-5-去甲阿里霉素的 4-氟衍生物的新合成和抗病毒评估。
DOI：
10.1016/j.bmc.2009.03.004
复制
发表时间：
2009
影响因子：
3.5
通讯作者：
Schneller,StewartW
中科院分区：
文献类型：
--
作者：
Yin,Xue-qiang;Li,Wei-kuan;Yang,Minmin;Schneller,StewartW
描述了通过氟化环戊醇合成（1 S，2S，3R，5S）-3-（6-氨基-9H-嘌呤-9-基）-5-氟环戊烷-1，2-二醇（即4′-脱氧-5 ′-去甲嘌呤霉素的4′-氟代衍生物3）的合成路线，这与现有的方案（一旦嘌呤环存在就发生取代反应）相反。测定化合物3对多种病毒的作用。观察到对麻疹的有利反应（中性红测定法中的IC 50为1.2μg/mL，目视测定法为14μg/mL），但这伴随着CV-1宿主细胞中的细胞毒性（21-36μg/mL）。不受3影响的病毒包括人巨细胞病毒和痘病毒（牛痘和牛痘），这三种病毒可被3的4′，4 ′-二氟类似物（即2）抑制。
A synthetic route to (1S,2S,3R,5S)-3-(6-amino-9H-purin-9-yl)-5-fluorocyclopentane-1,2-diol (that is, the 4′-fluoro derivative of 4′-deoxy-5′-noraristeromycin, 3) is described via a fluorinated cyclopentanol, which is in contrast to existing schemes where fluorination occurred once the purine ring was present. Compound 3 was assayed versus a number of viruses. A favorable response was observed towards measles (IC50of 1.2μg/mL in the neutral red assay and 14μg/mL by the visual assay) but this was accompanied by cytotoxicity in the CV-1 host cells (21–36μg/mL). Among the viruses unaffected by 3 were human cytomegalovirus and the poxviruses (vaccinia and cowpox), which are three viruses that were inhibited by the 4′,4′-difluoro analog of 3 (that is, 2).