Malkoti Nishkant, Meng Yifan, Zare Richard N, Gnanamani Elumalai
Department of Chemistry, Indian Institute of Technology Roorkee Roorkee 247667 India
Department of Chemistry, Stanford University Stanford CA 94305-5080 USA
Chem Sci. 2025 Jul 3. doi: 10.1039/d5sc03761a.
The unique environment of water microdroplets has enabled several novel organic transformations to be reported in recent years. Given the significance of the retro-Diels-Alder (rDA) reaction in organic and natural product synthesis, we demonstrate a highly accelerated rDA reaction using water microdroplets. The rDA reaction is a reversible process of the classical Diels-Alder cycloaddition, triggered by the dissociation of a six-membered ring, typically under thermal conditions. In this study, Diels-Alder adducts dissolved in water/methanol were electro-sprayed using nitrogen gas at a pressure of 120 psi, leading to efficient rDA product formation of benzoquinones. The products were characterized by mass spectrometry (MS) and tandem mass spectrometry (MS). Additionally, crude samples were collected after passage through a 40 mm heated channel (150 °C) for ≈1.2 ms in xylene solvents sprayed under 50 psi for 30 minutes, the distance between sprayer and collection chamber kept at 240 mm. The structures were further confirmed using MS, IR, H-NMR, and C-NMR analyses. Notably, 2.6 mg of the blue scorpion venom compound, 5-methoxy-2,3-bis(methylthio)cyclohexa-2,5-diene-1,4-dione, was obtained in 60% isolated yield. This compound, originally isolated from scorpion venom, exhibits remarkable antimicrobial activity against and the priority pathogen . The products were formed within milliseconds, representing a significant rate enhancement compared to traditional bulk-phase rDA reactions.
近年来，水微滴的独特环境使得一些新型有机转化反应得以报道。鉴于逆狄尔斯-阿尔德（rDA）反应在有机合成和天然产物合成中的重要性，我们展示了一种利用水微滴实现的高度加速的rDA反应。rDA反应是经典狄尔斯-阿尔德环加成反应的可逆过程，通常在热条件下由六元环的解离引发。在本研究中，将溶解于水/甲醇中的狄尔斯-阿尔德加合物在120 psi的氮气压力下进行电喷雾，从而高效地形成了苯醌的rDA产物。产物通过质谱（MS）和串联质谱（MS）进行表征。此外，在二甲苯溶剂中于50 psi压力下喷雾30分钟，喷雾器与收集室之间的距离保持在240 mm，使样品通过一个40 mm长、150 °C的加热通道约1.2 ms后收集粗样品。通过MS、红外光谱（IR）、氢核磁共振（H-NMR）和碳核磁共振（C-NMR）分析进一步确认了结构。值得注意的是，以60%的分离产率获得了2.6 mg蓝色蝎子毒液化合物5-甲氧基-2,3-双（甲硫基）环己-2,5-二烯-1,4-二酮。该化合物最初从蝎子毒液中分离得到，对[具体病原体1]和主要病原体[具体病原体2]表现出显著的抗菌活性。产物在数毫秒内形成，与传统的本体相rDA反应相比，反应速率有显著提高。
