ICIQ, Institute of Chemical Research of Catalonia, The Barcelona Institute of Science and Technology, Avenida Països Catalans 16, 43007, Tarragona, Spain.
University Rovira i Virgili, 43007, Tarragona, Spain.
Angew Chem Int Ed Engl. 2022 Oct 24;61(43):e202212176. doi: 10.1002/anie.202212176. Epub 2022 Sep 14.
Asymmetric catalytic cascade processes offer direct access to complex chiral molecules from simple substrates and in a single step. In biocatalysis, cascades are generally designed by combining multiple enzymes, each catalyzing individual steps of a sequence. Herein, we report a different strategy for biocascades based on a single multifunctional enzyme that can promote multiple stereoselective steps of a domino process by mastering distinct catalytic mechanisms of substrate activation in a sequential way. Specifically, we have used an engineered 4-oxalocrotonate tautomerase (4-OT) enzyme with the ability to form both enamines and iminium ions and combine their mechanisms of catalysis in a complex sequence. This approach allowed us to activate aldehydes and enals toward the synthesis of enantiopure cyclohexene carbaldehydes. The multifunctional 4-OT enzymes could promote both a two-component reaction and a triple cascade characterized by different mechanisms and activation sequences.
不对称催化级联反应为从简单底物一步直接构建复杂手性分子提供了可能。在生物催化中，级联反应通常通过组合多个酶来设计，每个酶催化序列中的单个步骤。在此，我们报道了一种基于单个多功能酶的生物级联的不同策略，该酶可以通过顺序掌握不同的底物激活催化机制，来促进多米诺反应的多个立体选择性步骤。具体来说，我们使用了一种工程化的 4-氧代戊烯酸互变异构酶（4-OT），该酶能够形成烯胺和亚胺离子，并将它们的催化机制结合在一个复杂的序列中。这种方法使我们能够激活醛和烯醛，以合成对映纯环己烯甲醛。多功能 4-OT 酶可以促进由不同机制和激活序列表征的两个组件反应和三重级联。
