6857-22-3

Upstream product

• 106-31-0 butanoic acid anhydride 
• 14131-63-6 D-glucosamine hydrochloride 
• 90-76-6 2-deoxy-2-amino glucose 
• 7165-13-1 acetic butyric anhydride 
• 1078691-95-8 (+)-D-glucosamine hydrochloride 
• 70741-39-8 2,5-dioxopyrrolidin-1-yl butyrate 
• 66-84-2 D-(+)-glucosamine hydrochloride 
• 107-92-6 butyric acid 
• 7512-17-6 N-Acetyl-D-glucosamine 

Relevant academic research and scientific papers

An Enzymatic N-Acylation Step Enables the Biocatalytic Synthesis of Unnatural Sialosides

Chitin is one of the most abundant and cheaply available biopolymers in Nature. Chitin has become a valuable starting material for many biotechnological products through manipulation of its N-acetyl functionality, which can be cleaved under mild conditions using the enzyme family of de-N-acetylases. However, the chemoselective enzymatic re-acylation of glucosamine derivatives, which can introduce new stable functionalities into chitin derivatives, is much less explored. Herein we describe an acylase (CmCDA from Cyclobacterium marinum) that catalyzes the N-acylation of glycosamine with a range of carboxylic acids under physiological reaction conditions. This biocatalyst closes an important gap in allowing the conversion of chitin into complex glycosides, such as C5-modified sialosides, through the use of highly selective enzyme cascades.

Highly efficient and selective biocatalytic production of glucosamine from chitin

N-Acetyl glucosamine (GlcNAc) is one of the most abundant biomolecules on Earth and is cheaply available from chitin, a major component of crustaceans. The key step in the conversion of GlcNAc to high-value products is the de-N-acetylation to glucosamine, in itself a valuable dietary supplement that is produced at over 29:000 tons scale per annum by chemical hydrolysis, a process that requires harsh reaction conditions and leads to side products requiring separation. Here, we report for the first time the isolation and characterisation of an enzyme, a deacetylase from Cyclobacterium marinum that is able to catalyse the highly selective quantitative hydrolysis of GlcNAc to glucosamine under mild reaction conditions. This enzyme is small (38 kDa), is easily obtainable by heterologous expression in E. coli, has high turnover rates (kcat=61 s-1), tolerates high substrate concentrations (over 100 g L-1) and can be repeatedly re-used as an immobilised catalyst. When coupled with chitinase, the high selectivity of the enzyme for GlcNAc over other biomolecules allowed one-pot extraction of glucosamine from crude solid mushroom fractions containing chitin, thus allowing for alternative production of glucosamine from non-animal sources, of benefit to consumers with crustacean allergies and vegan diets. We suggest that the deacetylase fills an important gap in the sustainable exploitation of GlcNAc and chitin.

Synthesis and characterization of N-acyl-tetra-O-acyl glucosamine derivatives

Novel 1,3,4,6-tetra-O-acyl-N-acyl-d-glucosamine derivatives were synthesized from glucosamine hydrochloride (GlcN·HCl) by the acylation with pyridine as a catalyst. A derivative of tetra-O-acetyl glucosamine contained ketoprofen, a non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects, was first synthesized. In analysis of the NMR spectra, the ratio of α:β-anomer showed that penta-acyl-d- glucosamine derivatives and N-acetylated glucosamines containing O-acyl groups have been only the α-anomer. Meanwhile, both the intermediates and the glucoconjugate compound of ketoprofen have only the β-anomer.

A chemoenzymatic route to N-acetylglucosamine-1-phosphate analogues: Substrate specificity investigations of N-acetylhexosamine 1-kinase

Reports an efficient chemoenzymatic production of an N-acetylhexosamine 1-phophate analogues library by N-acetylhexosamine 1-kinase (NahK) and describes the respective substrate specificity on this enzyme.

Sialic acid and N-acyl sialic acid analog production by fermentation of metabolically and genetically engineered Escherichia coli

Sialic acid is the terminal sugar found on most glycoproteins and is crucial in determining serum half-life and immunogenicity of glycoproteins. Sialic acid analogs are antiviral therapeutics as well as crucial tools in bacterial pathogenesis research, immunobiology and development of cancer diagnostic imaging. The scarce supply of sialic acid hinders production of these materials. We have developed an efficient, rapid and cost effective fermentation route to access sialic acid. Our approach uses low cost feedstock, produces an industrially relevant amount of sialic acid and is scalable to manufacturing levels. We have also shown that precursor directed biosynthesis can be used to produce a N-acyl sialic acid analog. This work demonstrates the feasibility of engineering manufacturing-friendly bacteria to produce complex, unavailable small molecules. The Royal Society of Chemistry.

N-butyryl glucosamine increases matrix gene expression by chondrocytes

Proteoglycan synthesis is dependent on N-acetyl glucosamine (GlcNAc) produced by the hexosamine biosynthetic pathway or obtained exogenously. Although used therapeutically to relieve symptoms of osteoarthritis, the actions of glucosamine and its analogs on cartilage are poorly understood. The purpose of this study was to determine the effects on chondrocytes of N-acylated-glucosamine analogs bearing alkyl chains of different lengths. Chondrocytes isolated from neonatal rat femoral condyles were cultured in the presence of glucosamine analogs. GlcNAc, N-proprionyl glucosamine (GlcNPro), or N-butyryl glucosamine (GlcNBu) did not alter cell number, lactate dehydrogenase release, or metabolic acid production, consistent with lack of cytotoxicity. Treatment of chondrocyte cultures with GlcNBu for 6 days significantly increased levels of type II collagen and aggrecan mRNA as determined by Northern blot analysis. In contrast, GlcNAc and GlcNPro had no significant effect. A significant increase in type II collagen mRNA was induced by GlcNBu within 3 days. GlcNBu did not alter stability of type II collagen mRNA, suggesting it acts on gene transcription. We have previously shown that tumor necrosis factor-α (TNFα) decreases levels of type II collagen mRNA. However, chondrocytes pretreated with GlcNBu maintained type II collagen mRNA at control levels in the presence of TNFα. These results establish that the N-butyrylated analog of glucosamine but not GlcNAc promotes matrix gene expression by chondrocytes. Thus, GlcNBu has the potential for use as a chondro-protective agent in osteoarthritis.

Synthesis and antiperoxidant activity of new phenolic O-glycosides

We describe the synthesis of some 3-tert-butyl-4-hydroxyphenyl D-glycopyranosides by reaction of tert-butylhydroquinone with β-D-pentaacetyl-glucose, β-D-pentaacetyl-galactose, 2-acetamido- and 3,4,6-tri-O-acetyl-2-butanamido-2-deoxy-β-D-glucopyranosyl chlorides as well as the formation of anomeric 3-tert-butyl-4-hydroxyphenyl 4,6-di-O-acetyl-2,3-dideoxy-D-erythro-hex-2-eno-pyranosides by reaction between tert-butylhydroquinone and 3,4,6-tri-O-acetyl-D-glucal. All compounds, except 3-tert-butyl-4-hydroxyphenyl α- and β-D-glucopyranosides, inhibited lipid peroxidation with a degree of potency comparable to that of tert-butyl hydroxyanisole.