Amino substituted derivatives of 5'-amino-5'-deoxy-5'-noraristeromycin.
Amino substituted derivatives of 5'-amino-5'-deoxy-5'-noraristeromycin.
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5-氨基-5-脱氧-5-去甲雷斯特霉素的氨基取代衍生物。
DOI：
10.1016/j.bmc.2004.10.031
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Schneller,StewartW
中科院分区：
文献类型：
--
作者：
Yang,Minmin;Schneller,StewartW
5′-氨基-5 ′-脱氧-5 ′-去甲红霉素（2）的强效抗病毒潜力受到相关毒性的限制。为了寻找避免这种不希望的性质的2的衍生物，已经从相同的中间体（1 S，4 R）-4-（6-氯嘌呤-9-基）环庚-2-烯-1-醇（6）在4-7个步骤中制备了2的三种氨基取代的衍生物（乙酰基，3;甲酰基，4;和甲基，5）。关键步骤包括改进的Pd（0）催化的烯丙基叠氮化反应和新的Pd（0）催化的烯丙基酰胺化反应。针对大量病毒评价了三种目标化合物，发现除了5对人巨细胞病毒、水痘带状疱疹病毒和爱泼斯坦-巴尔病毒的作用非常弱外，其余均无活性。也没有与新衍生物相关的值得注意的细胞毒性。因此，这些结果表明2的环戊基胺的变化不能提供改善其抗病毒潜力的手段。
The potent antiviral potential of 5′-amino-5′-deoxy-5′-noraristeromycin (2) is limited by associated toxicity. To seek derivatives of 2 that circumvent this undesirable property, three amino substituted derivatives (acetyl, 3; formyl, 4; and methyl, 5) of 2 have been prepared in 4–7 steps from the same intermediate, (1S,4R)-4-(6-chloropurin-9-yl)cyclopent-2-en-1-ol (6). Key steps involved an improved Pd(0)-catalyzed allylic azidation and a novel Pd(0)-catalyzed allylic amidation. The three target compounds were evaluated against a large number of viruses and found to be inactive except for a very weak effect of 5 on human cytomegalovirus, varicella zoster virus, and Epstein–Barr virus. There was also no noteworthy cytotoxicity associated with the new derivatives. Thus, these results indicate variation of the cyclopentyl amine of 2 does not offer a means to improve upon its antiviral potential.