New reaction pathways by integrating chemo- and biocatalysis

Abstract

The combination of chemo- and biocatalysis in one pot (integrated catalysis) can serve as an environmentally benign substitute for classical chemical methods. Enzymes and chemocatalysts are often complementary and their combination can enable completely new chemical transformations. Compartmentalisation strategies allow mutual inactivation of otherwise incompatible chemo- and biocatalysts to be overcome. Transition metals and organocatalysts have been successfully merged with biocatalysis, taking advantage of the broad scope of chemocatalysts and the exquisite regio-, stereo-, and enantioselectivity of enzymes. The combination of photoredox and enzymatic catalysis has been found to enable elusive chemical transformations. Moreover, biocatalysts and photocatalysts can act synergistically and enable non-natural enzyme reactivities. The combination of chemo- and biocatalysis in one pot (integrated catalysis) is a powerful approach to develop new routes towards important products under mild and environmentally benign reaction conditions. Integrated catalysis can improve overall synthetic efficiency and, due to the complementary nature of chemo- and biocatalysts, transformations can be performed, which would be otherwise challenging using a single catalyst. In this review, we highlight recent trends for the combination of enzymes with chemocatalysts. Transition-metal catalysis, organocatalysis, and photoredox catalysis have been combined with different biocatalysts and are discussed accordingly. We highlight further how integrated catalysis not only delivers benign substitutes for known transformations but moreover enables transformations that would be otherwise impossible. The combination of chemo- and biocatalysis in one pot (integrated catalysis) is a powerful approach to develop new routes towards important products under mild and environmentally benign reaction conditions. Integrated catalysis can improve overall synthetic efficiency and, due to the complementary nature of chemo- and biocatalysts, transformations can be performed, which would be otherwise challenging using a single catalyst. In this review, we highlight recent trends for the combination of enzymes with chemocatalysts. Transition-metal catalysis, organocatalysis, and photoredox catalysis have been combined with different biocatalysts and are discussed accordingly. We highlight further how integrated catalysis not only delivers benign substitutes for known transformations but moreover enables transformations that would be otherwise impossible. a stable (persistent) aminooxyl radical often used as a single-electron oxidant. chemocatalysts often enable broad substrate scopes and functional group tolerance. The selectivity of enzymes achieved through the 3D architecture of their active site is often beyond the reach of chemical methods, but they often suffer from limited substrate scope. Hence, the pros and cons of bio- and chemocatalysis complement each other well. a one-pot reaction with at least two successive reactions in which all reagents and catalysts are present from the beginning and the product is formed through two or more sequential noninterfering catalytic processes in a linear cascade. interconnected reactions that rely on other concurrent processes in such a way that yields and selectivity cannot be achieved if the reactions are conducted in a sequential manner. This can occur by a catalyst maintaining a dynamic equilibrium or enhancing the reactivity of a second catalyst. immobilised enzymes prepared via cross-linking with difunctional cross-linkers such as glutaraldehyde. CLEAs can enhance the overall stability and productivity of enzymes while also allowing enzyme recycling due to the heterogeneous nature of immobilisation. a system in which multiple catalysts perform sequences of reactions in a one-pot process without external interruption (i.e., isolation of intermediates). This may include spatial or temporal separation of catalysts. self-assembling nanosized (usually with particle size in the range 10–100 nm) colloidal dispersions with a hydrophobic core and hydrophilic shell. the performance of successive (or multiple) chemical transformations in the same reaction vessel without isolation of intermediates. lipophilic polymers that allow the physical separation of reaction vessels by flux exclusion of charged and hydrophilic molecules, while allowing diffusion of PDMS-soluble motifs across the membrane. a one-pot reaction with at least two reactions in succession, which requires additional manipulation such as catalyst/reagent addition, solvent changes, pH adjustments, degassing, or protein removal. designer surfactant DL-α-tocopherol methoxypolyethylene glycol succinate, comprising a lipophilic vitamin E core, a succinic acid linker, and a hydrophilic polyethylene glycol tail.