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    张梦思, 李保君, 李竞, 胡爱国. 伯胺对烯二炔化合物的Michael加成反应[J]. 华东理工大学学报(自然科学版), 2018, (5): 670-674,706. DOI: 10.14135/j.cnki.1006-3080.20171113003
    引用本文: 张梦思, 李保君, 李竞, 胡爱国. 伯胺对烯二炔化合物的Michael加成反应[J]. 华东理工大学学报(自然科学版), 2018, (5): 670-674,706. DOI: 10.14135/j.cnki.1006-3080.20171113003
    ZHANG Meng-si, LI Bao-jun, LI Jing, HU Ai-guo. Michael Addition of Primary Amine to Enediyne Compounds[J]. Journal of East China University of Science and Technology, 2018, (5): 670-674,706. DOI: 10.14135/j.cnki.1006-3080.20171113003
    Citation: ZHANG Meng-si, LI Bao-jun, LI Jing, HU Ai-guo. Michael Addition of Primary Amine to Enediyne Compounds[J]. Journal of East China University of Science and Technology, 2018, (5): 670-674,706. DOI: 10.14135/j.cnki.1006-3080.20171113003

    伯胺对烯二炔化合物的Michael加成反应

    Michael Addition of Primary Amine to Enediyne Compounds

    • 摘要: 烯二炔类小分子可在常温下发生Bergman环化反应而产生双自由基中间体,并表现出强烈的细胞毒性,成为抗肿瘤抗生素的重要选择。选取一种含有长链烷基的烯二炔作为模型化合物,研究了含有马来酰亚胺基团的烯二炔小分子的Michael加成反应。结果表明,在极性溶剂中,伯胺选择进攻烯二炔的叁键部分形成了无Bergman反应活性的1,6-单加成产物,而在低极性溶剂中或者伯胺上有大体积取代基的情况下,Michael加成反应被极大地抑制。水相体系中的实验证明,中性有利于促进Michael加成反应,在弱酸性条件下,烯二炔不被伯胺进攻,保留了Bergman环化反应活性。研究结果将有助于指导烯二炔类抗生素的分子设计并构建具有临床应用价值的载药系统。

       

      Abstract: Due to the high reactivity of Bergman cyclization at ambient temperature which generates diradical intermediates and high cytotoxicity in physiological environments, enediyne compounds have emerged as a class of promising candidates in anticancer treatment. In this work, the enediyne containing long alkynyl chains was chosen as a model compound to study the Michael addition reaction of maleimide-based enediyne compounds. The results showed that in polar solvents, the triple bond moiety of enediyne was quickly attacked by primary amine to generate a 1, 6-addition product with no Bergman cyclization reactivity. While in nonpolar solvents or when a primary amine with bulky substituents was used, the Michael addition reaction was sluggish. Screening the reaction in aqueous solution showed that the Michael addition was preferred in neutral media. In weak acidic environment, the enediyne compound was intact and maintained its Bergman cyclization activity. The overall results provide an important guide for molecular design of enediyne compounds and show great promise in constructing smart enediyne antibiotics delivery system for potential clinical applications.

       

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