Indium-mediated atom-transfer and reductive radical cyclizations of iodoalkynes: synthesis and biological evaluation of HIV-protease inhibitors.
Indium-mediated atom-transfer and reductive radical cyclizations of iodoalkynes: synthesis and biological evaluation of HIV-protease inhibitors.
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DOI：
10.1021/jo035482m
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发表时间：
2004-02
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影响因子：
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通讯作者：
R. Yanada;Y. Koh;Nobuaki Nishimori;A. Matsumura;Shingo Obika;H. Mitsuya;N. Fujii;Y. Takemoto
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文献类型：
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作者：
R. Yanada;Y. Koh;Nobuaki Nishimori;A. Matsumura;Shingo Obika;H. Mitsuya;N. Fujii;Y. Takemoto
已经研究了新型的铟介导的脂肪族碘代炔的自由基环化反应。用催化量的In（0.1当量）和I(2)（0.05当量）处理碘炔可促进原子转移5-外环化，得到五元烯基碘化物。相反，与In（2当量）和I(2)（1当量）的反应通过相同的5-外环化产生还原性5-外环化产物。这两个过程很可能都是由低价铟物质引发的。为了证明这些反应的多功能性，通过这种还原环化方法合成了光学活性 HIV 蛋白酶抑制剂。其中，含有羟乙胺二肽电子等排物作为模拟过渡态子结构的几种产品，被证明对多种 HIV 病毒株（包括多重耐药变体）具有有效活性 (IC(50) = 5-39 nM)。
Novel indium-mediated radical cyclization reactions of aliphatic iodoalkynes have been studied. Treatment of iodoalkynes with a catalytic amount of In (0.1 equiv) and I(2) (0.05 equiv) promotes atom-transfer 5-exo cyclization to give five-membered alkenyl iodides. In contrast, reaction with In (2 equiv) and I(2) (1 equiv) yields reductive 5-exo cyclization products via the same 5-exo cyclization. Both processes are most likely initiated by low-valent indium species. To demonstrate versatility of these reactions, optically active HIV protease inhibitors were synthesized by this reductive cyclization method. Among them, several products, which contain a hydroxyethylamine dipeptide isostere as a transition state-mimicking substructure, proved to possess potent activity (IC(50) = 5-39 nM) against a wide spectrum of HIV strains, including multidrug-resistant variants.