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Updated: Feb 10, 2026
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Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
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Two-Step Synthesis of a Chiral Fluorinated Alcohol With Silica-Supported Enzyme RrADH in Batch and Continuous Flow
Egzon Cermjani1,2, Greta Nölke3, Stefano Di Fiore3
1Fraunhofer Institute for Microengineering and Microsystems IMM, Mainz, Germany.
Chemistry (Weinheim an Der Bergstrasse, Germany)
|February 9, 2026
Summary
This study integrates continuous flow and biocatalysis to synthesize chiral fluoroalcohols, key pharmaceutical building blocks. The efficient two-step process achieves high yields and enantiomeric excess, paving the way for green pharmaceutical synthesis.
Area of Science:
- Green Chemistry
- Biocatalysis
- Flow Chemistry
Background:
- Growing demand for sustainable synthesis of chiral building blocks, especially fluoroalcohols for APIs.
- Need for efficient and selective methods to produce high-quality chiral fluoroalcohols.
Purpose of the Study:
- To integrate a two-step synthesis of (R)-2-fluoro-1-phenylethanol in a continuous flow system.
- To demonstrate the performance of immobilized enzymes in a continuous flow process for chiral fluoroalcohol synthesis.
Main Methods:
- Decarboxylative fluorination of 3-oxo-3-phenylpropanoic acid in aqueous media.
- Enantioselective biocatalytic reduction using immobilized Alcohol Dehydrogenase (ADH) from Rhodococcus ruber (RrADH).
- Continuous flow reactor system with a serial micro batch reactor (SMBR) setup and capillary reactor.
Main Results:
- Achieved excellent enantiomeric excess (> 99.9%) and overall yields up to 91% for both synthesis steps.
- Demonstrated operational and storage stability of immobilized RrADH.
- Successfully implemented a continuous two-step process with precise temperature control.
Conclusions:
- The integrated continuous flow and biocatalysis approach offers high efficiency and selectivity for chiral fluoroalcohol synthesis.
- This sustainable and versatile process is suitable for the green synthesis of fluorinated building blocks for pharmaceutical applications.
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