Enzyme-Friendly\nSolvent for One-Pot Chemobiocatalytic\nValorization of Fructose into Valuable Furanics via 5‑Hydroxymethylfurfural

Direct conversion of inexpensive fructose into value-added\nfuranic\nchemicals via chemobiocatalytic cascades is a highly attractive yet\nchallenging task due to the incompatibility issues between chemo-\nand biocatalysts. Among the issues, the solvent is crucial to make\nthe two worlds of catalysts work well in one pot. In this work, we\npresent an enzyme-friendly natural deep eutectic solvent (NADES)-based\nmedium for the one-pot chemobiocatalytic valorization of fructose\ninto valuable furanics via 5-hydroxymethylfurfural (HMF). HMF was\nobtained with approximately 40% yield and 64% selectivity within 1.5\nh under 150 °C in 15 wt % NADES (choline chloride/oxalic acid,\n1:1, mol/mol) aqueous solution. HMF selectivity was significantly\nimproved to approximately 91% by applying 15 vol % methyl isobutyl\nketone/NADES biphasic medium. A NADES/unreacted fructose recycle process\nwas designed to improve both the fructose overall conversion (77%)\nand HMF overall yield (72%). The NADES-based medium was benign toward\nvarious biocatalysts such as alcohol and aldehyde dehydrogenases,\nacyltransferase, and ω-transaminase, evidenced by good yields\n(86–97%) of the desired products in subsequent biotransformations.\nSpecifically, 2,5-bis(hydroxymethyl)furan was obtained from fructose\nwith a 41% isolated yield in gram-scale synthesis. This work may lay\nthe foundation for the sustainable manufacture of high-value furanics\nfrom biomass.