{"id":"doi:10.1002/chem.202503304","kind":"article","title":"Two-Step Synthesis of a Chiral Fluorinated Alcohol With Silica-Supported Enzyme RrADH in Batch and Continuous Flow Mode","authors":["Cermjani E","Nölke G","Fiore SD","Deckers C","Hanselmann D","Herbig B","Wintzheimer S","Rehm TH"],"author_count":8,"year":2026,"published":"2026-02-09","venue":"Chemistry (Weinheim an der Bergstrasse, Germany)","cited_by":0,"doi":"10.1002/chem.202503304","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1002/chem.202503304","archive_url":"https://space-kitty.com/papers/doi:10.1002/chem.202503304","updated":null,"pmid":"41660812","pmcid":"PMC13109679","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13109679/pdf","abstract":"The growing demand for sustainable and efficient methods for synthesizing fine chemicals has increased interest in innovative approaches for accessing high-quality chiral building blocks, particularly fluoroalcohols, which are relevant for the production of active pharmaceutical ingredients (APIs). This study presents the complete integration of a two-step process in a continuous flow reactor system for the synthesis of (R)-2-fluoro-1-phenylethanol as a reference molecule. To this end, the individual reaction steps and technologies for the decarboxylative fluorination of 3-oxo-3-phenylpropanoic acid in aqueous media, followed by an enantioselective biocatalytic reduction of the prochiral intermediate phenacyl fluoride, were adapted and implemented in a compact laboratory system for performance demonstration. Alcohol dehydrogenase (ADH) from Rhodococcus ruber (RrADH) produced in a plant-derived BY2 cell-free expression system was used as the biocatalyst, which was immobilized via an imine bond on glutaraldehyde-modified silica supraparticles. The immobilized enzymes were used in batch mode for comprehensive kinetic studies of the enantioselective reduction, including evaluations of their operational and storage stability. Excellent enantiomeric excess (> 99.9%) and overall yields of up to 91% were achieved for both synthesis steps. These results are a prerequisite for the targeted and stable use of the enzyme in a continuously operated two-step process, which was achieved by using a serial micro batch reactor (SMBR) setup with a capillary reactor for precise temperature control. This study demonstrates the advantages of combining immobilized biocatalysts with continuous-flow operation for achieving high efficiency and selectivity in the synthesis of chiral fluoroalcohols. The integrated process provides a sustainable and versatile basis for future developments in the green synthesis of fluorinated building blocks relevant to pharmaceutical applications.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Two-Step Synthesis of a Chiral Fluorinated Alcohol With Silica-Supported Enzyme RrADH in Batch and Continuous Flow Mode\" by Cermjani E, Nölke G, Fiore SD et al., https://doi.org/10.1002/chem.202503304, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"synthetic-biology","name":"Synthetic Biology & Genome Engineering","domain_slug":"biotech"}],"cited_in_dossiers":[]}