Chemoenzymatic access to enantiopure N-containing furfuryl alcohol from chitin-derived N-acetyl-D-glucosamine

Abstract

Background Chiral furfuryl alcohols are important precursors for the synthesis of valuable functionalized pyranones such as the rare sugar L-rednose. However, the synthesis of enantiopure chiral biobased furfuryl alcohols remains scarce. In this work, we present a chemoenzymatic route toward enantiopure nitrogen-containing (R)- and (S)-3-acetamido-5-(1-hydroxylethyl)furan (3A5HEF) from chitin-derived N-acetyl-D-glucosamine (NAG). Findings 3-Acetamido-5-acetylfuran (3A5AF) was obtained from NAG via ionic liquid/boric acid-catalyzed dehydration, in an isolated yield of approximately 31%. Carbonyl reductases from Streptomyces coelicolor (ScCR) and Bacillus sp. ECU0013 (YueD) were found to be good catalysts for asymmetric reduction of 3A5AF. Enantiocomplementary synthesis of (R)- and (S)-3A5HEF was implemented with the yields of up to > 99% and the enantiomeric excess (ee) values of > 99%. Besides, biocatalytic synthesis of (R)-3A5HEF was demonstrated on a preparative scale, with an isolated yield of 65%. Conclusions A two-step process toward the chiral furfuryl alcohol was successfully developed by integrating chemical catalysis with enzyme catalysis, with excellent enantioselectivities. This work demonstrates the power of the combination of chemo- and biocatalysis for selective valorization of biobased furans. Graphic abstract

Engineering carbonyl reductase for one-pot chemobiocatalytic enantioselective synthesis of a value-added N-containing chiral alcohol from N-acetyl-d-glucosamine

“…It, in turn, highlights the great advantages of a one-pot chemobiocatalytic process over two-pot chemoenzymatic synthesis requiring intermediate (3A5AF) isolation. 27 The E factor (35.4) obtained from the chemical dehydration reaction was more than 4-fold of that (7.9) obtained from enzymatic reduction. The E factor may be considerably reduced by optimizing synthesis and purification processes as well as by recycling catalysts and solvents.…”

“…5). Compared to our recent two-pot chemoenzymatic route, 27 this chemobiocatalytic approach provided a higher yield (53% vs. 31%) and led to decreased solvent consumption and waste generation, because of no requirement of isolating the intermediate 3A5AF.…”

“…It was recently found that Streptomyces coelicolor CR (ScCR) could accept 3A5AF as a substrate, but its specific activity remains very low (approximately 5.6 mU mg −1 protein). 27 On the other hand, a great improvement in the tolerance of this enzyme toward unfriendly environments (e.g., non-aqueous solvents and chemical catalysts) of chemical dehydration is in demand. The crystal structure of this enzyme (PDB ID: 5H5X) was solved.…”

“…20 Recently, our group reported the chemoenzymatic synthesis of ( R )- and ( S )-3A5HEF from NAG; although high enantioselectivity was achieved by harnessing biocatalysts, the isolation of the intermediate 3A5AF was required (Scheme 1), resulting in reduced overall synthetic efficiency as well as increased solvent consumption and waste production. 27 Therefore, we envisage that a direct chemobiocatalytic cascade incorporating sequential chemical dehydration of NAG and biocatalytic reduction of 3A5AF may be of great interest, as no isolation of intermediates is required. It was recently found that Streptomyces coelicolor CR ( Sc CR) could accept 3A5AF as a substrate, but its specific activity remains very low (approximately 5.6 mU mg −1 protein).…”

(Chemo)biocatalytic Upgrading of Biobased Furanic Platforms to Chemicals, Fuels, and Materials: A Comprehensive Review

“…Recently, our group reported the chemoenzymatic access to enantiopure N-containing FAL from chitin-derived N -acetyl- d -glucosamine (NAG) via sequential ionic liquid/boric acid-catalyzed dehydration and enzymatic asymmetric reduction, with the isolation of the intermediate 3-acetamido-5-acetylfuran (3A5AF) (Scheme ). Sc CR and CR from Bacillus sp. ECU0013 (YueD) were found to be appropriate catalysts for the asymmetric reduction of 3A5AF, affording ( R )- and ( S )-3-acetamido-5-(1-hydroxylethyl)­furan (3A5HEF) with >86% yields and >99% ee, respectively (Table , entry 10).…”