Rare Sugar Research Articles

Safety evaluation and maximum use level for transient ingestion in humans of allitol.

Allitol is a hexitol produced by reducing the rare sugar D-allulose with a metal catalyst under hydrogen gas. To confirm the safe level of allitol, we conducted a series of safety assessments. From the results of Ames mutagenicity assay using Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, Escherichia coli strain WP2uvrA, and an in vitro chromosomal aberration test on cultured Chinese hamster cells, allitol did not show any significant genotoxic effect. No significant effects on general condition, urinalysis, hematology, physiology, histopathology, or at necropsy were observed at a dose of 1,500 mg/kg body weight of allitol in the acute and 90-day sub-chronic oral-toxicity assessments for rats. A further study performed on healthy adult humans showed that the acute use level of allitol for diarrhea was 0.2 g/kg body weight for both men and women. The results of current safety assessment studies suggest that allitol is safe for human consumption.

Total Synthesis of 6-Deoxy-l-talose Containing a Pentasaccharide Repeating Unit of Acinetobacter baumannii K11 Capsular Polysaccharides.

Herein, we report a concise synthetic approach for the first total synthesis of a pentasaccharide repeating unit of Acinetobacter baumannii K11 capsular polysaccharides containing a rare sugar 6-deoxy-l-talose. The pentasaccharide was synthesized in a convergent manner using a [3 + 2] block glycosylation strategy. During this synthetic strive, we used a 2,2,2-trichloroethoxycarbonyl (Troc)-protected monosaccharide unit to achieve a high yield during the glycosylation to synthesize a trisaccharide, and chemoselective deprotection of the Troc group from the trisaccharide was carried out under a mild, pH-neutral condition, keeping the O-glycosidic bond, azido, and acid/base sensitive group intact. A thiotolylglycoside disaccharide donor containing 6-deoxy-l-talose was synthesized for the first time by the armed-disarmed glycosylation method between two thiotolylglycosides.

Synthesis of l-Rare Sugars from d-Sorbitol Using a TiO2 Photocatalyst

In recent years, l-rare sugars have been attracting attention, both as active compounds and useful building blocks for use in the pharmaceutical industry; however, these compounds have low natural abundances and cannot be extracted from natural products. Therefore, it is necessary to convert widely available substrates, such as biomass-derived compounds, to produce rare sugars. In this study, we examined the production of l-rare sugars using a TiO2 photocatalyst. d-Sorbitol was treated with a TiO2 photocatalyst under light irradiation, and the products were identified as glucose, gulose, fructose, sorbose, arabinose, xylose, erythrose, threose, and glyceraldehyde using high-performance liquid chromatography, liquid chromatography–mass spectrometry, and proton nuclear magnetic resonance spectroscopy. Furthermore, the production of the l-rare sugars, l-gulose and l-xylose, was confirmed by optical rotation measurements. Analysis of the product concentrations as a function of time suggested that d-sorbitol undergoes a decarbonization reaction and C–C bond cleavage when treated with a TiO2 photocatalyst.

Feedback Inhibition of Bacterial Nucleotidyltransferases by Rare Nucleotide l-Sugars Restricts Substrate Promiscuity.

Bacterial glycomes are rich in prokaryote-specific or "rare" sugars that are absent in mammals. Like common sugars found across organisms, rare sugars are typically activated as nucleoside diphosphate sugars (NDP-sugars) by nucleotidyltransferases. In bacteria, the nucleotidyltransferase RmlA initiates the production of several rare NDP-sugars, which in turn regulate downstream glycan assembly through feedback inhibition of RmlA via binding to an allosteric site. In vitro, RmlA activates a range of common sugar-1-phosphates to produce NDP-sugars for biochemical and synthetic applications. However, our ability to probe bacterial glycan biosynthesis is hindered by limited chemoenzymatic access to rare NDP-sugars. We postulate that natural feedback mechanisms impact nucleotidyltransferase utility. Here, we use synthetic rare NDP-sugars to identify structural features required for regulation of RmlA from diverse bacterial species. We find that mutation of RmlA to eliminate allosteric binding of an abundant rare NDP-sugar facilitates the activation of noncanonical rare sugar-1-phosphate substrates, as products no longer affect turnover. In addition to promoting an understanding of nucleotidyltransferase regulation by metabolites, this work provides new routes to access rare sugar substrates for the study of important bacteria-specific glycan pathways.

Total Synthesis of the Repeating Units of Proteus penneri 26 and Proteus vulgaris TG155 via a Common Disaccharide.

Herein, we report the first total synthesis of the trisaccharide and tetrasaccharide repeating units of P. penneri 26 and P. vulgaris TG155, respectively, having a common disaccharide unit, 3-α-l-QuipNAc-(1 → 3)-α-d-GlcpNAc-(1 →. Striking features of the targets are the presence of rare sugar units, l-quinovosamine and l-rhamnosamine, all joined through α-glycosidic linkages. Major challenges in the formation of 1,2-cis glycosidic linkages in the case of d-glucosamine, l-quinovosamine, and d-galactosamine have been addressed.

Fluorinated Analogues to the Pentuloses of the Pentose Phosphate Pathway.

Fluorinated carbohydrates are valuable tools for enzymological studies due to their increased metabolic stability compared to their non-fluorinated analogues. Replacing different hydroxyl groups within the same monosaccharide by fluorine allows to influence a wide range of sugar-receptor interactions and enzymatic transformations. In the past, this principle was frequently used to study the metabolism of highly abundant carbohydrates, while the metabolic fate of rare sugars is still poorly studied. Rare sugars, however, are key intermediates of many metabolic routes, such as the pentose phosphate pathway (PPP). Here we present the design and purely chemical synthesis of a set of three deoxyfluorinated analogues of the rare sugars d-xylulose and d-ribulose: 1-deoxy-1-fluoro-d-ribulose (1DFRu), 3-deoxy-3-fluoro-d-ribulose (3DFRu) and 3-deoxy-3-fluoro-d-xylulose (3DFXu). Together with a designed set of potential late-stage radio-fluorination precursors, they have the potential to become useful tools for studies on the complex equilibria of the non-oxidative PPP.

Production of d-aldotetrose from l-erythrulose using various isomerases.

d-Aldotetroses are rare sugars that are obtained via chemical synthesis in low yield. In this study, we demonstrated that d-aldotetroses could be produced using 3 isomerases. First, l-erythrulose was epimerized using d-tagatose 3-epimerase from Pseudomonas cichorii ST-24. The specific optical rotation of the reaction solution gradually decreased to zero, indicating that approximately 50% of the l-erythrulose was converted to d-erythrulose. d, l-Erythrulose mixture was isomerized with d-arabinose isomerase from Klebsiella pneumoniae 40bXX to produce d-threose, resulting in a conversion rate of 9.35%. d-Erythrose production using l-rhamnose isomerase from Pseudomonas stutzeri LL172 resulted in a conversion rate of 12.9%. Because of the low purity of the purchased d-erythrose, the product was reduced by the Raney nickel catalyst compared with authentic erythritol. We confirmed the products using HPLC and 13C-NMR spectra. This is the first report of d-aldotetrose production using an enzymatic reaction.

Influence of rare sugar syrup on quality attributes and acceptability of bread

SummaryRare sugar syrup (RSS) prepared by alkaline isomerisation of high‐fructose corn syrup (HFCS) contains rare sugars as well as D‐glucose (Glc) and D‐fructose (Fru) and has antiobesity and antidiabetic effects. RSS was used in making bread, and the quality of the final bread product was compared with bread with added sucrose (Suc). 20°Bx RSS‐ and 20°Bx HFCS‐added breads had lower loaf height and volume, moisture content and water activity compared with 20°Bx Suc‐added bread and had higher hardness and gumminess of bread crumb. In contrast, adding 2°Bx RSS did not affect the physical and texture characteristics of the bread. GC–MS analysis of the RSS‐added bread showed that acetol, 3,5‐dihydroxy‐6‐methyl‐2,3‐dihydro‐4H‐pyran‐4‐one, 5‐methylfurfural and acetic acid were the main volatiles, and the amounts were higher than in the Suc‐ and HFCS‐added breads. The addition of 20°Bx RSS resulted in the lowest liking scores for the bread texture, hardness and elasticity. The RSS‐added bread, with a lower evaluation than the 20°Bx Suc‐added bread, was acceptable in overall preference as the 20°Bx HFCS‐added bread. Moreover, after processing, the 20°Bx RSS‐bread retained 86% of the rare sugar D‐allulose with its health functions, so it could be beneficial to consumer health compared with HFCS and Suc.

Arginine-catalyzed isomerization of ribose to ribulose

Arginine, one of the basic amino acids known as green catalysts for sugar isomerization, was used to isomerize ribose to ribulose, a rare keto-pentose sugar, and the effects of reaction conditions on the yield of ribulose and degree of browning were investigated using a batch-type reactor. The initial pH of the mixture of ribose and arginine was in the range of 9.39–10.01. A high yield of ribulose and low degree of browning of the reaction mixture were achieved at a molar ratio of arginine to ribose of 0.05 and a temperature of 110 °C. To achieve the highest possible ribulose concentration, an initial ribose concentration of 0.75 mol/L was preferable. It was found that once isomerization had progressed, acidic by-products caused a reduction in pH and brown-colored compounds were continuously formed. This study showed that the method used is relatively simple and effective for producing ribulose.

Scalable Synthesis of Versatile Rare Deoxyamino Sugar Building Blocks from d-Glucosamine.

We report the syntheses of 1,3,4-tri-O-acetyl-2-amino-2,6-dideoxy-β-d-glucopyranose and allyl 2-amino-2,6-dideoxy-β-d-glucopyranoside from d-glucosamine hydrochloride. The potential of these two versatile scaffolds as key intermediates to a diversity of orthogonally protected rare deoxyamino hexopyranosides is exemplified in the context of fucosamine, quinovosamine, and bacillosamine. The critical C-6 deoxygenation step to 2,6-dideoxy aminosugars is performed at an early stage on a precursor featuring an imine moiety or a trifluoroacetamide moiety in place of the 2-amino group, respectively. Robustness and scalability are demonstrated for a combination of protecting groups and incremental chemical modifications that sheds light on the promise of the yet unreported allyl 2,6-dideoxy-2-N-trifluoroacetyl-β-d-glucopyranoside when addressing the feasibility of synthetic zwitterionic oligosaccharides. In particular, allyl 3-O-acetyl-4-azido-2,4,6-trideoxy-2-trifluoroacetamido-β-d-galactopyranoside, an advanced 2-acetamido-4-amino-2,4,6-trideoxy-d-galactopyranose building block, was achieved on the 30 g scale from 1,3,4,6-tetra-O-acetyl-β-d-glucosamine hydrochloride in 50% yield and nine steps, albeit only two chromatography purifications.

Intestinal absorption of D-fructose isomers, D-allulose, D-sorbose and D-tagatose, via glucose transporter type 5 (GLUT5) but not sodium-dependent glucose cotransporter 1 (SGLT1) in rats.

D-allulose, D-sorbose and D-tagatose are D-fructose isomers that are called rare sugars. These rare sugars have been studied intensively in terms of biological production and food application as well as physiological effects. There are limited papers with regard to the transporters mediating the intestinal absorption of these rare sugars. We examined whether these rare sugars are absorbed via sodium-dependent glucose cotransporter 1 (SGLT1) as well as via GLUT type 5 (GLUT5) using rats. High-fructose diet fed rats, which express more intestinal GLUT5, exhibited significantly higher peripheral concentrations, Cmax and AUC0–180 min when D-allulose, D-sorbose and D-tagatose were orally administrated. KGA-2727, a selective SGLT1 inhibitor, did not affect the peripheral and portal vein concentrations and pharmacokinetic parameters of these rare sugars. The results suggest that D-allulose, D-sorbose and D-tagatose are likely transported via GLUT5 but not SGLT1 in rat small intestine.

Conditioned preference and avoidance induced in mice by the rare sugars isomaltulose and allulose

Isomaltulose, a slowly digested isocaloric analog of sucrose, and allulose, a noncaloric fructose analog, are promoted as "healthful" sugar alternatives in human food products. Here we investigated the appetite and preference conditioning actions of these sugar analogs in inbred mouse strains. In brief-access lick tests (Experiment 1), C57BL/6 (B6) mice showed similar concentration dependent increases in licking for allulose and fructose, but less pronounced concentration-dependent increases in licking for isomaltulose than sucrose. In Experiment 2, B6 mice were given one-bottle training with a CS+ flavor (e.g., grape) mixed with 8% isomaltulose or allulose and a CS- flavor (e.g., cherry) mixed in water followed by two-bottle CS flavor tests. The isomaltulose mice showed only a weak CS+ flavor preference but a strong preference for the sugar over water. The allulose mice strongly preferred the CS- flavor and water over the sugar. The allulose avoidance may be due to gut discomfort as reported in humans consuming high amounts of the sugar. Experiment 3 found that the preference for 8% sucrose over 8% isomaltulose could be reversed or blocked by adding different concentrations of a noncaloric sweetener mixture (sucralose + saccharin, SS) to the isomaltulose. Experiment 4 revealed that the preference of B6 or FVB/N mice for isomaltulose+0.01%SS or sucrose over 0.1%SS increased after separate experience with the sugars and SS. This indicates that isomaltulose, like sucrose, has postoral appetition effects that enhances the appetite for the sugar. In Experiments 5 and 6, the appetition actions of the two sugars were directly compared by giving mice isomaltulose+0.05%SS vs. sucrose choice tests before and after separate experience with the two sugars. In general, the initial preference the mice displayed for isomaltulose+0.05%SS was reduced or reversed after separate experience with the two sugars although some strain and sex differences were obtained. This indicates that isomaltulose has weaker postoral appetition effects than sucrose.

Resistance: Stories from World War II France by Édith Thomas, and: Résistance: Contes de la seconde Guerre mondiale en France par Édith Thomas

Reviewed by: Resistance: Stories from World War II France by Édith Thomas, and: Résistance: Contes de la seconde Guerre mondiale en France par Édith Thomas E. Nicole Meyer Thomas, Édith. Resistance: Stories from World War II France. Trans. Michelle Chilcoat. MLA, 2022. ISBN 978-1-60329-502-4. Pp. 65. Thomas, Édith. Résistance: Contes de la seconde Guerre mondiale en France. Ed. Michelle Chilcoat. MLA, 2022. ISBN 978-1-60329-499-7. Pp. 67. Paired with the French original offered as a companion text, this edition of stories "transcrit[s] du réel" offers instructors and students the opportunity to read Thomas's narratives that reveal responses of ordinary people to extraordinary choices during the Vichy-Nazi era. Originally published anonymously in 1943 under the title Contes d'Auxois by what was then a clandestine publishing house founded by the Thomas and two other members of the Resistance, Les Éditions de Minuit, the stories offered alternative views to the Vichy and Nazi propaganda dropped from airplanes or handed out to French citizens. Thomas chose to serve the Resistance through her words, in the hope of inspiring others to resist the current path towards destruction of death, "des cimetières et des camps de concentration, l'ordre moral des morts" to quote Thomas (viii). "Que peut-on faire?" she wrote in 1940 (viii). These stories pose a cogent answer. Thanks to Chilcoat's new English translation and the updated French companion complete with detailed historical footnotes, we have the opportunity to share a contemporaneous narrative of the difficult choices faced on a daily basis by French citizens during World War II. Furthermore, women's stories of contemporary wartime events were rare, so this edition makes a wonderful companion to World War II-related works by women, for instance, Marguerite Duras's La douleur (1985) and other women's recounting of their war experience, published decades after the war. In one story, an elderly man waits for hours in line with the unlikely chance of bringing home some mussels or tripe for his wife. Her kind act of preparing tea with a rare sugar cube to warm him up after his failure brings him joy. In another, "The Relief" / "La Relève," the accuracy of description is stunning. As I have studied the actual Vichy propaganda designed to encourage the French to go to Germany in order to replace Germans sent to the Russian front, the details of the various pamphlets and images ring true. Thomas describes how "volunteers" soon transformed into "mandatory volunteers" ordered to go. Thus, these men and their companions faced untenable choices as they postponed the inevitable violence to come. Other stories bring back from Germany hints of what is to come if one supports Pétain's and Hitler's programs as well as the dangers of being caught if one resists. Beautifully written, Thomas captures indelible, quiet moments. For instance, "Night Watch" begins with "The Wind has picked up from the west and a full moon gallops behind the clouds above. Trees arch their naked backs along both sides of the road. All is movement and stillness" (22). These two volumes would complement many French literature courses or serve as examples of translation for students pursuing such a focus. With these seven tales, Thomas offers [End Page 182] us the chance to better understand the gray area that sometimes appears between resisting and collaborating as well as the courage required to decide what to do when faced with the difficult decisions the French faced during World War II. [End Page 183] E. Nicole Meyer Augusta University (GA) Copyright © 2023 American Association of Teachers of French

Highly efficiency production of D-allulose from inulin using curli fiber multi-enzyme cascade catalysis

D-Allulose is a rare sugar with numerous physiological benefits and low caloric content, which can be obtained from inulin through enzymatic catalysis. In this study, we combined D-allulose 3-epimerase, exo- and endo-inulinases (EXINU and ENINU) with the NGTag/NGCatcher/CsgA system to accelerate D-allulose accumulation from inulin. Molecular dynamics simulations were used to screen linkers of appropriate length for ENINU. In vitro, we successfully observed the assembled NGCatcher_ENINU_CsgA, NGTag_EXINU, and DAERK fibers using fluorescent labelling with GFP, YFP, and mCherry. The optimal pH and temperature of the tagged variants were comparable to those of the wild-type, and the MD simulations showed that NGCatcher_ENINU_CsgA had improved stability in the working environment of EXINU. D-Allulose accumulation rate of the assembled enzymes cascade (NGCatcher_ENINU_CsgA/NGTag_EXINU_CsgA/DAERK) reached 0.25 g/L min−1 (1.25 mgD-allulose mgDAERK−1 min−1) at an inulin concentration of 100 g/L. The assembled system greatly improves the high-valued productions of rare sugars from cheap biomass.

Total Synthesis of Trisaccharide Repeating Unit of Staphylococcus aureus Strain M

An efficient total synthesis of a conjugation-ready trisaccharide repeating unit of Staphylococcus aureus strain M is reported here. The main challenges involved in this synthesis are the procurement of rare sugars (d-FucNAc and d-GalNAcA) and installation of consecutive 1,2-cis-glycosidic linkages between them. Stereoselective 1,2-cis glycosylation with the linker acceptor was achieved with easily accessible benzylidene protected d-galactosamine thioglycoside by employing a DMF modulated preactivation glycosylation method. The consecutive 1,2-cis linkages were installed with the help of solvent participation. The carboxylic acid functionality was introduced via postglycosylation oxidation on the disaccharide moiety. The total synthesis of trisaccharide repeating unit was accomplished with the longest linear sequence of 24 steps in 4.5% overall yield.

Allulose for the attenuation of postprandial blood glucose levels in healthy humans: A systematic review and meta-analysis.

D-Allulose is a rare sugar that exists in nature. It is a food ingredient with nearly zero calories (<0.4 kcal/g) and has many physiological functionalities such as attenuation of postprandial blood glucose levels, attenuation of postprandial fat mass accumulation, and anti-aging property. This study focused on the postprandial blood glucose changes in healthy humans by a systematic review and meta-analysis. They were chosen because of its importance to a prevention from diabetes. The study objective was to examine acute blood glucose concentrations of healthy humans after the meal with and without allulose. The study collected all D-allulose related studies from various databases. A forest plot of the comparison between an allulose intake group and the control group showed both 5g and 10g intake groups have the significantly smaller area under the curve of postprandial blood glucose levels. It means that D-Allulose attenuates postprandial blood glucose concentrations in healthy humans. As the result, D-Allulose is a valuable blood glucose management tool for healthy humans and diabetes patients. Allulose Diet enables reduction of sucrose intake through Sugar Reformulation in the future diet.

희소당 알룰로스의 침입외래식물 단풍잎돼지풀 생육 억제 효과 연구

희소당 알룰로스의 침입외래식물 단풍잎돼지풀 생육 억제 효과 연구

Chemoenzymatic Total Synthesis of Haemophilus ducreyi Lipooligosaccharide Core Octasaccharides Containing Natural and Unnatural Sialic Acids

The first total synthesis of Haemophilus ducreyi lipooligosaccharide core octasaccharides containing natural and unnatural sialic acids has been achieved by an efficient chemoenzymatic approach. A highly convergent [3 + 3] coupling strategy was developed to chemically assemble a unique hexasaccharide bearing multiple rare higher-carbon sugars d-glycero-d-manno-heptose (d,d-Hep), l-glycero-d-manno-heptose (l,d-Hep), and 3-deoxy-α-d-manno-oct-2-ulosonic acid (Kdo). Key features include sequential one-pot glycosylations for oligosaccharide assembly and the construction of the challenging α-(1 → 5)-linked Hep-Kdo glycosidic bond by gold-catalyzed glycosylation with a glycosyl ortho-alkynylbenzoate donor. Furthermore, the sequential enzyme-catalyzed regio- and stereoselective introduction of a galactose residue using β-1,4-galactosyltransferase and different sialic acids using a one-pot multienzyme sialylation system was efficiently accomplished to provide the target octasaccharides.

Rare Sugar Metabolism and Impact on Insulin Sensitivity along the Gut-Liver-Muscle Axis In Vitro.

Rare sugars have recently attracted attention as potential sugar replacers. Understanding the biochemical and biological behavior of these sugars is of importance in (novel) food formulations and prevention of type 2 diabetes. In this study, we investigated whether rare sugars may positively affect intestinal and liver metabolism, as well as muscle insulin sensitivity, compared to conventional sugars. Rare disaccharide digestibility, hepatic metabolism of monosaccharides (respirometry) and the effects of sugars on skeletal muscle insulin sensitivity (impaired glucose uptake) were investigated in, respectively, Caco-2, HepG2 and L6 cells or a triple coculture model with these cells. Glucose and fructose, but not l-arabinose, acutely increased extracellular acidification rate (ECAR) responses in HepG2 cells and impaired glucose uptake in L6 cells following a 24 h exposure at 28 mM. Cellular bioenergetics and digestion experiments with Caco-2 cells indicate that especially trehalose (α1-1α), D-Glc-α1,2-D-Gal, D-Glc-α1,2-D-Rib and D-Glc-α1,3-L-Ara experience delayed digestion and reduced cellular impact compared to maltose (α1-4), without differences on insulin-stimulated glucose uptake in a short-term setup with a Caco-2/HepG2/L6 triple coculture. These results suggest a potential for l-arabinose and specific rare disaccharides to improve metabolic health; however, additional in vivo research with longer sugar exposures should confirm their beneficial impact on insulin sensitivity in humans.

Rational design of GDP‑d‑mannose mannosyl hydrolase for microbial l‑fucose production

Backgroundl‑Fucose is a rare sugar that has beneficial biological activities, and its industrial production is mainly achieved with brown algae through acidic/enzymatic fucoidan hydrolysis and a cumbersome purification process. Fucoidan is synthesized through the condensation of a key substance, guanosine 5′‑diphosphate (GDP)‑l‑fucose. Therefore, a more direct approach for biomanufacturing l‑fucose could be the enzymatic degradation of GDP‑l‑fucose. However, no native enzyme is known to efficiently catalyze this reaction. Therefore, it would be a feasible solution to engineering an enzyme with similar function to hydrolyze GDP‑l‑fucose.ResultsHerein, we constructed a de novo l‑fucose synthetic route in Bacillus subtilis by introducing heterologous GDP‑l‑fucose synthesis pathway and engineering GDP‑mannose mannosyl hydrolase (WcaH). WcaH displays a high binding affinity but low catalytic activity for GDP‑l‑fucose, therefore, a substrate simulation‑based structural analysis of the catalytic center was employed for the rational design and mutagenesis of selected positions on WcaH to enhance its GDP‑l‑fucose‑splitting efficiency. Enzyme mutants were evaluated in vivo by inserting them into an artificial metabolic pathway that enabled B. subtilis to yield l‑fucose. WcaHR36Y/N38R was found to produce 1.6 g/L l‑fucose during shake‑flask growth, which was 67.3% higher than that achieved by wild‑type WcaH. The accumulated l‑fucose concentration in a 5 L bioreactor reached 6.4 g/L.ConclusionsIn this study, we established a novel microbial engineering platform for the fermentation production of l‑fucose. Additionally, we found an efficient GDP‑mannose mannosyl hydrolase mutant for L‑fucose biosynthesis that directly hydrolyzes GDP‑l‑fucose. The engineered strain system established in this study is expected to provide new solutions for l‑fucose or its high value‑added derivatives production.