A plug-and-play chemobiocatalytic route for the one-pot controllable synthesis of biobased C4 chemicals from furfural

Chemobiocatalytic selective transformation is an attractive yet challenging task, due to the incompatibility issues between different types of catalysts. In this work, one-pot, multi-step cascades integrating biocatalysis with organo-, base- and photocatalysis in a plug-and-play fashion were constructed for the controllable synthesis of eight C4 chemicals from furfural. Furfural was converted to 5-hydroxy-2(5H)-furanone (HFO) by sequential biocatalytic oxidation and photooxygenation in phosphate buffer, in >90% yields. Ring opening and concurrent isomerization of HFO to fumaric semialdehyde (FSA) were readily realized under mild conditions by a weakly basic resin (e.g., DVB resin). The versatile intermediate FSA could be oxidized to fumaric acid (FA) using a laccase–2,2,6,6-tetramethylpiperidinyl-1-oxy (TEMPO) system, which was further upgraded to amino acids including L-aspartic acid (L-Asp) and β-alanine (β-Ala) by whole-cell catalysis. Notably, amino acids were obtained from biobased furfural in a one-pot, four-step process with yields of up to 75%, without the isolation of any intermediates. Besides, the scale-up synthesis of L-Asp was demonstrated. This work demonstrates the great potential of the combination of chemo- and biocatalysis for selective furfural valorization.