Enzyme-Friendly Solvent for One-Pot Chemobiocatalytic Valorization of Fructose into Valuable Furanics via 5-Hydroxymethylfurfural

Direct conversion of inexpensive fructose into value-added furanic chemicals via chemobiocatalytic cascades is a highly attractive yet challenging task due to the incompatibility issues between chemo- and biocatalysts. Among the issues, the solvent is crucial to make the two worlds of catalysts work well in one pot. In this work, we present an enzyme-friendly natural deep eutectic solvent (NADES)-based medium for the one-pot chemobiocatalytic valorization of fructose into valuable furanics via 5-hydroxymethylfurfural (HMF). HMF was obtained with approximately 40% yield and 64% selectivity within 1.5 h under 150 °C in 15 wt % NADES (choline chloride/oxalic acid, 1:1, mol/mol) aqueous solution. HMF selectivity was significantly improved to approximately 91% by applying 15 vol % methyl isobutyl ketone/NADES biphasic medium. A NADES/unreacted fructose recycle process was designed to improve both the fructose overall conversion (77%) and HMF overall yield (72%). The NADES-based medium was benign toward various biocatalysts such as alcohol and aldehyde dehydrogenases, acyltransferase, and ω-transaminase, evidenced by good yields (86–97%) of the desired products in subsequent biotransformations. Specifically, 2,5-bis(hydroxymethyl)furan was obtained from fructose with a 41% isolated yield in gram-scale synthesis. This work may lay the foundation for the sustainable manufacture of high-value furanics from biomass.