Synthesis of cyclopentenyl carbocyclic nucleosides as potential antiviral agents against orthopoxviruses and SARS
Synthesis of cyclopentenyl carbocyclic nucleosides as potential antiviral agents against orthopoxviruses and SARS
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DOI：
10.1021/jm0509750
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发表时间：
2006-02-09
影响因子：
7.3
通讯作者：
Chu, CK
中科院分区：
文献类型：
--
作者：
Cho, JH;Bernard, DL;Chu, CK
研究了手性环戊烯醇衍生物(+)-12a的合成方法，并将其作为合成具有生物活性的碳环核苷的关键中间体。烯丙基羟基的选择性保护，随后与Grubbs催化剂进行闭合环复分解（RCM）反应，在10 g规模上提供(+)-12a， d -核糖的总收率为52%(4)。利用关键中间体(+)-12a合成了非天然的五元环杂环碳环核苷。新合成的1,2,3-三唑类似物（17c）对牛痘病毒具有强抗病毒活性（EC50 0.4 μ M），对牛痘病毒和严重急性呼吸综合征冠状病毒（SARSCoV）具有中等抗病毒活性（EC50 39 μ M） （EC50 47 μ M）。1,2,4-三唑类似物（17a）对SARSCoV也表现出中等的抗病毒活性（EC50为21 μ M）。
A practical and convenient methodology for the synthesis of chiral cyclopentenol derivative (+)-12a has been developed as the key intermediate that was utilized for the synthesis of biologically active carbocyclic nucleosides. The selective protection of allylic hydroxyl group followed by the ring-closing metathesis (RCM) reaction with Grubbs catalysts provided (+)-12a on a 10 g scale with 52% overall yield from D-ribose (4). The key intermediate (+)-12a was utilized for the synthesis of unnatural five-membered ring heterocyclic carbocyclic nucleosides. The newly synthesized 1,2,3-triazole analogue (17c) exhibited potent antiviral activity (EC50 0.4 mu M) against vaccinia virus and moderate activities (EC50 39 mu M) against cowpox virus and severe acute respiratory syndrome coronavirus (SARSCoV) (EC50 47 mu M). The 1,2,4-triazole analogue (17a) also exhibited moderate antiviral activity (EC50 21 mu M) against SARSCoV.