Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai 200438, PR China.
Research Centre for Analysis and Measurement, Fudan University, 2005 Songhu Road, Shanghai 200438, PR China.
J Org Chem. 2022 Jan 7;87(1):464-478. doi: 10.1021/acs.joc.1c02484. Epub 2021 Dec 28.
Novel annulated azaheterocycles of benzo[1,2,4]triazoloazepine and tetrahydronaphtho[1,2-][1,2,4]triazine derivatives have been synthesized. Treatment of 2-diazenyl-1,2,3,4-tetrahydronaphthalen-2-yl acetates with BF·EtO generates 1-aza-2-azoniaallenium cation intermediates (or azocarbenium ions), which are intercepted by nitriles via cascade polar [3 + 2]-cycloaddition/rearrangement reactions to afford benzo[1,2,4]triazoloazepinium salts. These literature unprecedented fused tricycle compounds have been shown to exhibit antimicrobial activity against Gram-positive with in silico docking studies, suggesting that they may exhibit their antibiotic activity through inhibition of DNA gyrase. Additionally, when ethyl 2-(1-acetoxy-1,2,3,4-tetrahydronaphthalen-2-yl)diazene-1-carboxylate is employed, the reaction with BF·EtO produces 1,2-diaza-1,3-diene, which reacts with nitriles via a diaza-Diels-Alder reaction with inverse electron demand, leading to ethyl tetrahydronaphtho[1,2-][1,2,4]triazine carboxylates. The DFT calculation has been performed to further prove the D-A reaction speculation.
新型稠合氮杂芳环苯并[1,2,4]三唑并氮杂环庚因和四氢萘并[1,2-][1,2,4]三嗪衍生物已被合成。用 BF·EtO 处理 2-重氮基-1,2,3,4-四氢萘-2-基乙酸酯会生成 1-氮杂-2-氮杂烯翁阳离子中间体（或氮杂碳正离子），这些中间体通过级联极性[3+2]-环加成/重排反应与腈类反应，得到苯并[1,2,4]三唑并氮杂环庚因盐。这些文献中前所未有的稠合三环化合物表现出对革兰氏阳性菌的抗菌活性，并且通过计算机对接研究表明，它们可能通过抑制 DNA 拓扑异构酶发挥其抗生素活性。此外，当使用乙基 2-(1-乙酰氧基-1,2,3,4-四氢萘-2-基)重氮-1-羧酸酯时，与 BF·EtO 的反应会生成 1,2-二氮杂-1,3-二烯，该二烯与腈类通过逆电子需求的氮杂-Diels-Alder 反应反应，生成乙基四氢萘并[1,2-][1,2,4]三嗪羧酸酯。进行了 DFT 计算以进一步证明 D-A 反应的推测。
