Design, synthesis, and antiviral evaluation of some 3'-carboxymethyl-3'-deoxyadenosine derivatives.
Design, synthesis, and antiviral evaluation of some 3'-carboxymethyl-3'-deoxyadenosine derivatives.
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一些 3-羧甲基-3-脱氧腺苷衍生物的设计、合成和抗病毒评价。
DOI：
10.1080/15257770701426278
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
RobinsonJr,WEdward
中科院分区：
文献类型：
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作者：
Peterson,MattA;Ke,Pucheng;Shi,Houguang;Jones,Carl;McDougall,BrendaR;RobinsonJr,WEdward
以2'-O-TBDMS-3'-[(乙氧基羰基)甲基]-3'-脱氧腺苷(1)为原料，通过简单高效的工艺制备了3'-羧甲基-3'-脱氧腺苷衍生物。通过一种新颖的一锅法，采用 5'-活化 (TosCl)，然后用叠氮化四甲基胍进行有效的亲核置换，将 1 转化为 5'-叠氮基-5'-脱氧衍生物 5。化合物5经H2/Pd-C一锅还原/酰化，再用对硝基苯基N-甲基氨基甲酸酯处理，转化为5'-[(N-甲基氨基甲酰基)氨基]衍生物8。异氰酸苯酯处理引入N6-苯基氨基甲酰基，是2'-O-TBDMS-3'-[(乙氧基羰基)甲基]-3'-脱氧腺苷内酯化的高效新方法还开发了相应的2',3'-内酯。评估了目标化合物的抗 HIV 和抗 HIV 整合酶活性，但在测试浓度下没有活性。
3′-Carboxymethyl-3′-deoxyadenosine derivatives were prepared from 2′-O-TBDMS-3′-[(ethoxycarbonyl)methyl]-3′-deoxyadenosine (1) via simple and efficient procedures. Conversion of1to its 5′-azido-5′-deoxy derivative5was accomplished via a novel one-pot method employing 5′-activation (TosCl) followed by efficient nucleophilic displacement with tetramethylguanidinium azide. Compound5was converted to 5′-[(N-methylcarbamoyl)amino] derivative8via one-pot reduction/acylation employing H2/Pd-C followed by treatment withp-nitrophenylN-methylcarbamate.N6-phenylcarbamoyl groups were introduced by treatment with phenylisocyanate, and an efficient new method for lactonization of 2′-O-TBDMS-3′-[(ethoxycarbonyl)methyl]-3′-deoxyadenosines to give corresponding 2′,3′-lactones was also developed. Target compounds were evaluated for anti-HIV and anti-HIV integrase activities, but were not active at the concentrations tested.