Part-I: 一類四氫吡嗪并[2,1-a:5,4-a']二異喹啉衍生物在以水作為溶劑的環保條件下被成功合成。部分合成化合物的三維結構通過X射線繞射確定。由於天然存在的異喹啉生物鹼對包括冠狀病毒在內的多種病毒具有顯著的抗病毒活性，對所合成的化合物進行了針對SARS-CoV-2的抑制活性測試。結果顯示，活性化合物50和96分別通過抑制SARS-CoV-2刺突蛋白受體結合域（RBD）與人類受體血管緊張素轉化酶2（ACE2）之間的相互作用，阻止Delta SARS-CoV-2進入VeroE6細胞，表現出EC50值分別為26.5 ± 6.9和17.0 ± 3.7 μM，且CC50均大於100 μM。本研究為異喹啉的抗病毒或其他應用提供了一種綠色合成方法。

Part-II: 苯胺與β-氯酮的Michael加成反應通過消除鹽酸（HCl）生成烯胺酮。隨後，這些烯胺酮通過原位的sp² C-H官能化轉化為α-氯烯胺酮。苯胺上的電子供體基團能提高其與β-氯酮的反應性，生成對應產物並具有優異的產率。開發了一種高度原子經濟的方法，使用二甲基亞碸（DMSO）作為綠色氧化劑和溶劑。該方法可高效生成α-官能化烯胺酮，具有良好的產率和極高的Z-選擇性。通過多種底物驗證了該反應的普適性，並且放大實驗證明其實際應用價值。此外，還實現了在無催化劑的條件下，β-氯酮與鄰苯二胺的雙環化反應，可在溫和條件下合成1,4-苯二氮䓬衍生物，並取得中等產率。

Part-III: 一種合成1H-茚類化合物的級聯反應已被開發，通過2-苯乙烯基苯甲醛與吲哚反應實現。該過程包括碘催化的吲哚對2-苯乙烯基苯甲醛醛基的親核加成，形成碳陽離子中間體。這些中間體隨後經歷4π-電子環化反應，生成具有三取代雙鍵的茚類化合物。在反應條件下，這些茚類化合物進一步轉化為熱力學更穩定的全取代雙鍵產物。此外，反應還生成少量吲哚基苯并[b]咔唑類副產物。

关键词:

SARS CoV 2：嚴重急性呼吸系統綜合症
RBD：滾輪驅動
NSP：國際衛生戰略

Part-I: A class of tetrahydropyrazino[2,1-a:5,4-a']diisoquinoline derivatives were synthesized under an environmentally friendly condition using water as a solvent. The 3-D structures of some synthesized compounds were determined by X-ray diffraction. Since naturally occurring isoquinoline alkaloids have significant antiviral activities against a wide range of viruses, including coronaviruses, the synthesized compounds were assayed for their inhibitory activities against SARS-CoV-2. The results showed that the active compounds 50 and 96 blocked the delta SARS-CoV-2 entry into VeroE6 cells to display EC50 of 26.5 ± 6.9 and 17.0 ± 3.7 M, respectively, by inhibiting the interaction between SARS-CoV-2 Spike’s receptor binding domain (RBD) and human receptor angiotensin converting enzyme 2 (ACE2), and CC50 greater than 100 M. This study provides a green synthesis method of isoquinolines for antiviral or other applications.

Part-II: The Michael addition of anilines to β-chloroenones produces enaminones through the elimination of hydrochloric acid (HCl). These enaminones undergo in situ sp² C-H functionalization to yield α-chloroenaminones. The reactivity of anilines with β-chloroenones is significantly enhanced by electron-donating groups, enabling the formation of products with excellent yields. A highly atom-efficient method utilizing dimethyl sulfoxide (DMSO) as a green oxidant and solvent has been developed, offering α-functionalized enaminones with high yields and remarkable Z-selectivity. The reaction demonstrates broad substrate compatibility and scalability, highlighting its practical utility. Furthermore, a catalyst-free double annulation of β-chloroenones with o-phenylenediamine has been successfully implemented, facilitating the synthesis of 1,4-benzodiazepine derivatives in moderate yields under mild conditions.

Part-III: A cascade reaction has been developed for the synthesis of 1H-indenes by reacting 2-styrylbenzaldehydes with indoles. The process involves an iodine-catalyzed nucleophilic addition of indoles to the aldehyde group of 2-styrylbenzaldehydes, resulting in the formation of carbocation intermediates. These intermediates undergo 4π-electrocyclization to yield indenes with a trisubstituted double bond. Under the reaction conditions, these indenes are further transformed into more thermodynamically stable products with a fully substituted double bond. Minor amounts of indolylbenzo[b]carbazoles are also generated as byproducts.

Keywords: SARS CoV 2: Severe acute respiratory syndrome coronavirus 2
RBD: Receptor-Binding Domain
NSP: non-structural proteins

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