Efficient Lipase‐Catalyzed Synthesis at ≥100°C Through Biocatalyst Entrapment in a Porous Organic Polymer

ABSTRACT Enzymatic synthetic processes beyond the boiling point of water are regarded as extraordinarily challenging. Such a technology based on highly stable and recyclable biocatalysts would not only represent a remarkable scientific achievement, but also be valuable for organic‐synthetic chemistry and even have industrial relevance. Here we present a strategy that enables efficient biotransformations at ≥100°C under solvent‐free conditions with excellent process efficiency. A lipase, which has been encapsulated according to a modified protocol for immobilization within a covalent organic framework, remains catalytically active and structurally stable, allowing continuous operation and recycling over 12 consecutive cycles at 100°C with nearly constant conversion. Furthermore, this heterogeneous enzyme composite exhibits outstanding catalytic activity at 100°C, being about twice as high as that observed at room temperature. Electron diffraction revealed diffuse scattering, which indicates a predominantly amorphous structure of this enzyme immobilizate. The microenvironment of this porous organic polymer (POP) effectively prevents enzyme unfolding and provides a robust, reusable biocatalyst capable of processing molten mixtures of high‐melting substrates at ≥100°C in the absence of organic solvents. This concept expands the process window of biocatalysis toward direct utilization of high‐melting solids as molten substrate mixtures, which opens organic‐synthetic perspectives for improved cosmetic ester production in the chemical industry. Our work also illustrates how tailor‐made POP composites with entrapped lipases can bridge materials chemistry and sustainable catalysis for selective and efficient high‐temperature applications.