| 摘要: | 結合化學催化與生物催化之多步驟合成的方法近十年來快速發展，展現高產率、低成本、環保與高選擇性等優勢。然而，由於兩類催化反應在操作條件、試劑耐受性與溶劑環境上存在差異，整合於單一反應系統中仍具挑戰。分級金屬有機骨架（Hierarchical Metal-Organic Frameworks）具備微孔與中孔共存的結構特性，能有效分隔並穩定異質催化劑，特別適用於藥物中間體合成所需之串聯反應。麻黃鹼為具交感神經刺激作用的天然胺類藥物，廣泛應用於感冒與氣喘治療，其合成涉及多步驟反應，極需高選擇性與高效率的催化系統。為解決化學與酵素催化共存問題，本研究建構一雙層結構的分級MOF系統，先將鈀奈米粒子（Pd NPs）封裝於MIL-53-NH₂中形成Pd@MIL-53-NH₂，再透過溫和水相原位合成法（de novo approach），將酵素丙酮酸脫羧酶（PDC）與Pd@MIL-53-NH₂共同包覆於MOF-74中，成功合成(Pd@MIL-53-NH₂+PDC)@MOF-74複合材料。此設計可實現兩種催化功能共存，並有效解決反應條件不相容與催化活性干擾等問題，同時具備模擬生物體內反應之鄰近效應，提升效率與選擇性。另以(MIL-53-NH₂+CAT)@MOF-74為模型驗證其孔洞篩選與酵素保護功能，在proteinase K存在下仍可維持酵素活性，顯示本系統於未來製藥與綠色化學領域具高度應用潛力。;In the past decade, the integration of chemical and enzymatic catalysis for multi-step synthesis has advanced rapidly, offering significant advantages such as high yield, low cost, environmental friendliness, and excellent selectivity. However, due to distinct differences in reaction conditions, reagent tolerance, and solvent systems between these two catalytic domains, their combination within a single reaction system remains challenging. Hierarchical metal-organic frameworks (Hierarchical MOFs), featuring both micro- and mesoporous structures, provide an ideal platform for the spatial separation and stabilization of heterogeneous catalysts and are particularly suited for cascade reactions required in the synthesis of pharmaceutical intermediates.
Ephedrine is a naturally occurring amine with sympathomimetic effects, widely used in the treatment of colds and asthma. Its synthesis involves multiple steps and demands highly selective and efficient catalytic systems. To address the challenges of combining chemical and enzymatic catalysis, this study constructed a bilayer hierarchical MOF system. Palladium nanoparticles (Pd NPs) were first encapsulated within MIL-53-NH₂ to form a Pd@MIL-53-NH₂ composite. Using a mild aqueous-phase de novo synthesis approach, the enzyme pyruvate decarboxylase (PDC) and Pd@MIL-53-NH₂ were co-encapsulated into an MOF-74 outer shell, resulting in the formation of a (Pd@MIL-53-NH₂+PDC)@MOF-74 composite.
This design enables the coexistence of dual catalytic functions within a single system, effectively resolving issues related to incompatible reaction conditions and mutual catalytic interference. It also mimics proximity effects found in biological systems, thereby improving reaction efficiency and selectivity. Additionally, a (MIL-53-NH₂+CAT)@MOF-74 model system was developed to verify the material’s protective and size-selective properties, demonstrating that catalase activity can be maintained even in the presence of proteinase K. These findings highlight the strong potential of this hierarchical catalytic platform for future applications in pharmaceutical manufacturing and green chemistry. |
