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Direct Conversion of Hydrazones to Amines using Transaminases
Eve M Carter1, Fabiana Subrizi1, John M Ward2
1Department of Chemistry University College London 20 Gordon Street London WC1H 0AJ UK.
Chemcatchem
|July 25, 2022
Summary
This study introduces a novel method using transaminase enzymes to convert hydrazones into amine products. The addition of electrophiles and cofactors like PLP significantly improved amine yields, offering a new route for chiral amine synthesis.
Area of Science:
- Biocatalysis
- Organic Synthesis
- Enzymology
Background:
- Transaminase enzymes (TAms) are crucial biocatalysts for synthesizing optically pure amines from aldehydes and ketones.
- Traditional methods often require specific substrates and conditions for efficient amination.
Purpose of the Study:
- To explore a novel application of transaminases for the direct amination of hydrazones.
- To investigate factors influencing amine yield and explore the synthesis of chiral amines.
Main Methods:
- Direct reaction of transaminases with various hydrazone substrates, including those with furan and phenyl groups.
- Inclusion of electrophiles, pyridoxal 5'-phosphate (PLP), and polyethylene glycol (PEG)-aldehydes to optimize reaction conditions.
- Analysis of amine product yields and stereochemistry.
Main Results:
- Successful synthesis of amine products directly from hydrazones using transaminases.
- Increased amine yields observed with the addition of electrophiles, likely due to hydrazine sequestration.
- Pyridoxal 5'-phosphate (PLP) and PEG-aldehydes were found to enhance amine formation.
- Promising results for the synthesis of chiral β-substituted amines from (S)-(-)-1-amino-2-(methoxymethyl)pyrrolidine (SAMP) hydrazones.
Conclusions:
- Transaminase-mediated amination of hydrazones represents a novel and effective synthetic strategy.
- Optimizing reaction conditions with electrophiles and cofactors can significantly improve yields.
- This method provides a viable route for the enantioselective synthesis of valuable chiral amines.
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