Zhu Ran, Mo Xuhua, Gulder Tanja, Gulder Tobias A M
Chair of Technical Biochemistry, Department of Chemistry and Food Chemistry, Technical University of Dresden, Bergstraße 66, Dresden, 01069, Germany.
Biosystems Chemistry, Faculty of Chemistry, Technical University of Munich, Lichtenbergstraße 4, Garching, 85748, Germany.
Angew Chem Int Ed Engl. 2025 Aug 18;64(34):e202504378. doi: 10.1002/anie.202504378. Epub 2025 Jul 4.
The combination of bio- and chemo-catalytic processes has tremendous potential for the sustainable production of important synthetic building blocks. Such approaches capitalize on the often-high selectivity of enzymes and the broad arsenal of synthetic transformations to access highly functionalized molecules from simple precursors. However, the strict requirement of enzymes for an aqueous reaction environment, often combined with their lack of stability under harsh reaction conditions, makes the development of efficient chemo-enzymatic cascade reactions challenging. Within this work, we developed a chemo-enzymatic platform that combines regioselective enzymatic Halogenation, chemo-catalytic Heck coupling, and an enzyme-catalyzed Hydrolysis reaction (H Catalytic Platform = HCP) in a single reaction vessel. HCP uses water as a reaction solvent to facilitate the enzymatic transformations, with the cross-coupling reaction taking place in dynamic and protective super-molecular reaction vessels composed of the commercially available TPGS-705-M. Our work utilizes various halogenating enzymes (FDHs and VHPOs), selectively functionalizing diverse substrates, thus enabling subsequent metal-catalyzed cross-coupling followed by enzymatic hydrolysis. HCP gives access to a broad range of valuable acrylic acid building blocks with diverse functionalization at the aromatic portion.
生物催化与化学催化过程的结合在可持续生产重要合成砌块方面具有巨大潜力。此类方法利用了酶通常具有的高选择性以及丰富多样的合成转化手段，能够从简单前体获得高度官能化的分子。然而，酶对水相反应环境的严格要求，以及它们在苛刻反应条件下往往缺乏稳定性，使得开发高效的化学酶级联反应具有挑战性。在这项工作中，我们开发了一个化学酶平台，该平台在单个反应容器中结合了区域选择性酶促卤化、化学催化的Heck偶联反应和酶催化的水解反应（H催化平台 = HCP）。HCP使用水作为反应溶剂以促进酶促转化，交叉偶联反应则在由市售的TPGS - 705 - M组成的动态保护超分子反应容器中进行。我们的工作利用了各种卤化酶（FDHs和VHPOs），对多种底物进行选择性官能化，从而实现后续的金属催化交叉偶联反应及酶促水解反应。HCP能够获得一系列在芳香部分具有不同官能化的有价值的丙烯酸类砌块。
