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Recent Advances on the Use of 2-methyltetrahydrofuran (2-MeTHF) in Biotransformations

[ Vol. 5 , Issue. 2 ]


Andres R. Alcantara* and Pablo Dominguez de Maria*   Pages 86 - 103 ( 18 )


2-methyltetrahydrofuran (2-MeTHF) has become a broadly used (biogenic) solvent in organic synthesis, particularly with promising applications in biocatalysis, due to its excellent behaviour and favourable properties. 2-MeTHF may be derived from renewable sources - such as furfural or levulinic acid and its low water solubility facilitates its complete recovery in reactions in aqueous media, reducing wastes and simplifying the recycling and reuse. 2-MeTHF properties typically outperform those of traditional solvents (such as THF), enabling its application in a wide range of chemical and enzymatic synthetic processes. Remarkably, this trend can be observed not only in academia, but also at industrial scale, where companies start to assess 2-MeTHF for the replacement of non-GRAS solvents (Generally Regarded As Safe). Given that increasing importance, this mini-review discusses the recent advances in biocatalysis using 2-MeTHF, with applications for different enzymes (hydrolases, oxidoreductases, lyases, etc.), as well as in innovative combinations such as gas-liquid mixtures (CO2-2-MeTHF expanded phase), in multi-step enzymatic systems, and flow biocatalysis. The combination of 2-MeTHF with the intrinsic sustainability associated with biotransformations creates an attractive synergy.


2-methyltetrahydrofuran, biogenic solvents, biocatalysis, biotransformations, green chemistry, API.


Department of Chemistry in Pharmaceutical Sciences, Section of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, Complutense University of Madrid, Plaza de Ramon y Cajal, Madrid, Sustainable Momentum, SL. Av. Ansite 3, 4-6, Las Palmas Gran Canaria, Canary Islands

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