Enzymatic Knoevenagel condensation in dual‐functionalized water‐mimicking ionic liquids and tertiary amide solvents
Enzymatic Knoevenagel condensation in dual‐functionalized water‐mimicking ionic liquids and tertiary amide solvents
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在双官能化水中进行酶促 Knoevenagel 缩合，模拟离子液体和叔酰胺溶剂
DOI：
10.1002/jctb.7603
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发表时间：
2024
影响因子：
3.4
通讯作者：
Campbell, Chante' D.
中科院分区：
文献类型：
--
作者：
Zhao, Hua;Campbell, Chante' D.
Knoevenagel缩合是构建碳-碳（C → C）键的重要工具，特别是当被酶催化时，以实现潜在的高化学选择性、区域选择性和/或立体选择性。虽然许多Knoevenagel缩合反应在水溶液中进行，但不溶性疏水底物通常导致催化效率差。水混溶性有机溶剂的使用改善了底物的溶解，但通常会导致酶的活性抑制或失活。在C → C键形成反应中，非常需要开发用于底物溶解和酶相容性的替代溶剂。我们的团队先前开发了双官能化的仿水离子液体（IL），用于活化和稳定水解酶（例如脂肪酶和蛋白酶）。在本研究中，我们评估了4-氯苯甲醛与乙酰丙酮的Knoevenagel缩合反应，发现猪胰脂肪酶在携带铵、咪唑和苯并咪唑阳离子的仿水离子液体中能够实现更高的反应速率（高达3.22 μmol min−1g− 1脂肪酶）和比叔丁醇、甘醇二甲醚和[BMIM][Tf 2N]更好的产率。有趣的是，叔酰胺溶剂如N-甲基-2-吡咯烷酮（NMP）、N，N-二甲基甲酰胺（DMF）和N，N-二甲基乙酰胺（DMAc）导致初始速率增加8.2至11.1倍。（高达35.66 μmol min-1g-1脂肪酶），这可能是由于这些叔酰胺与脂肪酶的一些协同效应。与叔丁醇和甘醇二甲醚相比，咪唑鎓和苯并咪唑鎓阳离子提高了Knoevenagel缩合反应的速率和产率。叔酰胺（NMP，DMF和DMAc）显着增加反应速率。© 2024 The Authors.Journal of Chemical Technology and Biotechnology由John Wiley & Sons Ltd代表化学工业协会（SCI）出版。
BACKGROUNDKnoevenagel condensation is an important tool for building carbon–carbon (CC) bonds, especially when catalyzed by enzymes to enable a potentially high chemo‐, regio‐ and/or stereoselectivity. Although many Knoevenagel condensation reactions are carried out in aqueous solutions, insoluble hydrophobic substrates often lead to poor catalytic efficiencies. The use of water‐miscible organic solvents improves the substrate solubilization, but usually induces activity suppression or inactivation of enzymes. There is a great need to develop alternative solvents for both substrate dissolution and enzyme compatibility in CC bond formation reactions.RESULTSOur group previously developed dual‐functionalized water‐mimicking ionic liquids (ILs) for the activation and stabilization of hydrolases (e.g. lipase and protease). In the present study, we evaluated the Knoevenagel condensation of 4‐chlorobenzaldehyde with acetylacetone, and found that porcine pancreas lipase in water‐mimicking ILs carrying ammonium, imidazolium and benzimidazolium cations enabled higher reaction rates (up to 3.22 μmol min−1g−1lipase) and better yields thantert‐butanol, glymes and [BMIM][Tf2N]. Interestingly, tertiary amide solvents such asN‐methyl‐2‐pyrrolidone (NMP),N,N‐dimethylformamide (DMF) andN,N‐dimethylacetamide (DMAc) led to 8.2‐ to 11.1‐fold increases in the initial rate (up to 35.66 μmol min−1g−1lipase) when compared with dual‐functionalized ILs, which is likely due to some synergistic effect of these tertiary amides with the lipase.CONCLUSIONDual‐functionalized ILs based on ammonium, imidazolium and benzimidazolium cations improved Knoevenagel condensation reaction rates and yields when compared withtert‐butanol and glymes. Tertiary amides (NMP, DMF and DMAc) significantly increased the reaction rate. © 2024 The Authors.Journal of Chemical Technology and Biotechnologypublished by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).