Highly Efficient Production and Simultaneous Purification of Lactulose via Isomerization of Lactose through an Innovative Sustainable Anion-Extraction Process

Abstract

The traditional chemical isomerization of lactose into lactulose faces unfavorable thermodynamic limitations, significant side reactions, and high purification cost challenges. Herein, an efficient strategy for combining extraction-assisted isomerization and simultaneous purification of lactulose is presented. Under optimized conditions, 4-vinylphenylboronic acid (VPBA) favored the selective extraction of lactulose and up to 80% of lactulose can be extracted with a high selectivity (>95%). The extracted lactulose can be rapidly (<10 min) back-extracted into an acidic HCl solution as a concentrated lactulose stream (∼20 g/L). Lactulose purity can significantly be improved to 99.64% through a two-staged stripping process as a function of HCl contents. In situ removal of the newly formed lactulose catalyzed by Na 2 HPO 4 + NaOH through selective extraction could significantly promote lactulose yield and minimize the formation of byproducts. The applied extraction-assisted isomerization strategy enabled the yield of lactulose up to ∼70% (batch-extraction model) and ∼85% (in situ extraction model), with the lowest yield of byproducts (<5%) ever found. Remarkably, the VPBA-dominated organic phase and the catalyst-containing aqueous phase could be easily regenerated and reused multiple times, well proving their feasibility in clean and sustainable industrial applications. This trial validates for the first time the use of the extraction-assisted strategy for an effective simultaneous isomerization and isolation of high-purity lactulose.

Reactive extraction of fructose for efficient separation of sucrose-derived glucosides produced by enzymatic glycosylation

“…34 Unless mentioned, mixture of 1-octanol and hexane (4/1, v/v) was used as the organic phase. 1-Octanol is a good solvent for boronic acids, 25,31 however it exhibits a high viscosity, exacerbating the blending of aqueous and organic phase, which hampers the phase contact. Hexane is added to overcome this limitation.…”

“…This represents a notable improvement compared to previous studies, where sugar extraction was carried out with a high excess of boronic acid and Aliquat 336. 25,31,32 This condition was used further to develop the extraction process.…”

“…[25][26][27] Reactive extraction was previously intensively examined for the recovery of carboxylic acids (e.g., lactic and citric acid). [28][29][30] This method can be highly selective, 31 generally avoids product dilution 32 and has already been used for Fru recovery from different product mixtures. 25 Moreover, processes of reactive extraction are usually simple to operate and can be implemented well within existing process lines.…”

“…25 Moreover, processes of reactive extraction are usually simple to operate and can be implemented well within existing process lines. 31 Reactive extraction was shown for monosaccharide isolation in earlier studies, [33][34][35][36] but its application to separate Fru from sucrose-derived glucosides was not explored. The goal of the current study was the development of a dedicated separation process based on reactive extraction.…”

“…Moreover, disaccharides and larger oligosaccharides, apart from some exceptions like lactulose, are generally less well extracted than monosaccharides. 25,31,34 This is due to the occurrence of steric hindrance in disaccharides, preventing the complexation with organoboronic acids. 41 These considerations lent strong support to the idea that, by exploiting differential complexation with an organoboronic acid carrier, efficient separation of Fru and sucrose-derived glucoside might be achieved.…”