Branched-chain Amino Sugars Research Articles

The metabolomic signature of weight loss and remission in the Diabetes Remission Clinical Trial (DiRECT)

Aims/hypothesisHigh-throughput metabolomics technologies in a variety of study designs have demonstrated a consistent metabolomic signature of overweight and type 2 diabetes. However, the extent to which these metabolomic patterns can be reversed with weight loss and diabetes remission has been weakly investigated. We aimed to characterise the metabolomic consequences of a weight-loss intervention in individuals with type 2 diabetes.MethodsWe analysed 574 fasted serum samples collected within an existing RCT (the Diabetes Remission Clinical Trial [DiRECT]) (N=298). In the trial, participating primary care practices were randomly assigned (1:1) to provide either a weight management programme (intervention) or best-practice care by guidelines (control) treatment to individuals with type 2 diabetes. Here, metabolomics analysis was performed on samples collected at baseline and 12 months using both untargeted MS and targeted 1H-NMR spectroscopy. Multivariable regression models were fitted to evaluate the effect of the intervention on metabolite levels.ResultsDecreases in branched-chain amino acids, sugars and LDL triglycerides, and increases in sphingolipids, plasmalogens and metabolites related to fatty acid metabolism were associated with the intervention (Holm-corrected p<0.05). In individuals who lost more than 9 kg between baseline and 12 months, those who achieved diabetes remission saw greater reductions in glucose, fructose and mannose, compared with those who did not achieve remission.Conclusions/interpretationWe have characterised the metabolomic effects of an integrated weight management programme previously shown to deliver weight loss and diabetes remission. A large proportion of the metabolome appears to be modifiable. Patterns of change were largely and strikingly opposite to perturbances previously documented with the development of type 2 diabetes.Data availabilityThe data used for analysis are available on a research data repository (https://researchdata.gla.ac.uk/) with access given to researchers subject to appropriate data sharing agreements. Metabolite data preparation, data pre-processing, statistical analyses and figure generation were performed in R Studio v.1.0.143 using R v.4.0.2. The R code for this study has been made publicly available on GitHub at: https://github.com/lauracorbin/metabolomics_of_direct.Graphical

Diabetes Leads to Alterations in Normal Metabolic Transitions of Pregnancy as Revealed by Time-Course Metabolomics.

Women with diabetes during pregnancy are at increased risk of poor maternal and neonatal outcomes. Despite this, the effects of pre-gestational (PGDM) or gestational diabetes (GDM) on metabolism during pregnancy are not well understood. In this study, we utilized metabolomics to identify serum metabolic changes in women with and without diabetes during pregnancy and the cord blood at birth. We observed elevations in tricarboxylic acid (TCA) cycle intermediates, carbohydrates, ketones, and lipids, and a decrease in amino acids across gestation in all individuals. In early gestation, PGDM had elevations in branched-chain amino acids and sugars compared to controls, whereas GDM had increased lipids and decreased amino acids during pregnancy. In both GDM and PGDM, carbohydrate and amino acid pathways were altered, but in PGDM, hemoglobin A1c and isoleucine were significantly increased compared to GDM. Cord blood from GDM and PGDM newborns had similar increases in carbohydrates and choline metabolism compared to controls, and these alterations were not maternal in origin. Our results revealed that PGDM and GDM have distinct metabolic changes during pregnancy. A better understanding of diabetic metabolism during pregnancy can assist in improved management and development of therapeutics and help mitigate poor outcomes in both the mother and newborn.

Synthesis of new branched-chain amino sugars

1,3-Dipolar cycloaddition of methylideneaniline N-oxide to sugar enones is described. The addition occurred exclusively from the side opposite to the aglycone affording the corresponding alkyl α- d- lyxo-hexopyranosid-(2,3:5′,4′)-phenylisoxazolidin-4-uloses. Hydrogenation of these compounds readily yielded the corresponding alkyl 3-deoxy-3- N-phenylaminomethyl-α- d-talopyranoside, that were readily transformed to the acetates. The structure and conformation of the bicyclic compounds were determined by 1H NMR studies and semi-empirical molecular orbital calculations employing the AM1 method.

A new stereoselective route to branched-chain nitro and amino sugars: synthesis of both enantiomers of decilonitrose and avidinosamine

Short, efficient, and highly diastereoselective syntheses of the title carbohydrates (15, 21, and 22), components of new anthracycline antibiotics, on a gram scale from readily available keto sugar precursors 6 and 17 are described. The syntheses feature the smooth and clean addition of organocerium compounds to benzyloxyimino derivatives 7 and 18; which provide the branched-chain hydroxyamino sugars (9, 20) bearing an equatorial methyl group with complete regio- and stereocontrol. Treatment of oximino deoxy sugars (7, 18) with methyllithium resulted in β-elimination and afforded pyranoid 1-enol 3-one oximes (8, 19)

Synthesis of branched-chain sugars: A stereoselective route to sibirosamine, kansosamine, and vinelose from a common precursor

Methyl 4,6-dideoxy-3- C-methyl-4-( N-methyl- N-phenylsulfonylamino)-α- l-mannopyranoside and methyl 4-amino-4,6-dideoxy-3- C-methyl-α- l-mannopyranoside, derivatives of the branched-chain amino sugars sibirosamine and kansosamine, respectively, were synthesized by nucleophilic ring-opening of methyl 3,4-anhydro-6-deoxy-3- C-methyl-α- l-talopyranoside. Catalytic reduction of methyl 6-deoxy-2,3- O-isopropylidene-3- C-methyl-α- l- lyxo-hexopyranosid-4-ulose gave the axial alcohol methyl 6-deoxy-2,3- O-isopropylidene-3- C-methyl-α- l-talopyranoside, a known precursor to vinelose.

A route to functionalized branched-chain amino sugars via nitrous acid promoted spiroaziridine formation

A route to functionalized branched-chain amino sugars via nitrous acid promoted spiroaziridine formation

Synthesis of novel branched-chain amino sugars: methyl l-sibirosaminide and N-acylkansosamine

Methyl l-sibirosaminide and N-acylkansosamine were synthesized via the same intermediate, methyl 4-amino-4,6-dideoxy-2,3- O-isopropylidene-3- C-methyl-α- l-mannopyranoside ( 7), from l-rhamnose in 7 and 10 steps, respectively. Conversion of 7 into the title compounds was performed by N-methylation or N-(2-methoxypropanoyl)ation followed by appropriate derivatization.

Branched-chain Sugars. XXXVI. A New Synthesis of Methyl 4-O-Benzoyl-3-benzoylamino-2,3,6-trideoxy-3-C-methyl-α-l-xylo-hexopyranoside, a Derivative of the Branched-chain Amino Sugar of Antibiotic A35512B

Abstract The title compound was synthesized from methyl 4-O-benzyl-2,6-dideoxy-β-l-threo-hexopyranosid-3-ulose (19) through cyanomesylation, reductive spiro aziridine formation, and reductive ring-opening. When (2-methoxyethoxymethyl) group was used as the protecting group at O-4 of the above intermediate, it could not be removed at the final stage.

A stereochemically defined route to branched-chain amino sugars, via spirooxiranes, and related studies

A stereochemically defined route to branched-chain amino sugars, via spirooxiranes, and related studies

ChemInform Abstract: A NOVEL SYNTHESIS OF A BRANCHED‐CHAIN AMINO SUGAR, METHYL 2‐AMINO‐2,3‐DIDEOXY‐3‐C‐FORMYL‐α‐D‐XYLOFURANOSIDE‐3′R,5‐HEMIACETAL

AbstractDas aus dem Glucopyranosid (Ia) erhältliche Derivat (Ib) wird in die Derivate (Ic)+(II) bzw. die Verbindung (III) übergeführt.

Branched-chain sugars. Part 16. The synthesis of a derivative of 3-amino-2,3,6-trideoxy-3-C-methyl-L-xylo-hexopyranose, the novel branched-chain amino sugar of antibiotic A35512B

Methyl 2,6-dideoxy-4-O-methoxymethyl-α-L-erythro-hexopyranosid-3-ulose (1) reacted with potassium cyanide under equilibrating conditions to give methyl 3-C-cyano-2,6-dideoxy-4-O-methoxymethyl-α-L-arabino-hexopyranoside (11). The mesylate (12) derived from this cyanohydrin was converted by established procedures, although not without difficulty, into methyl 3-acetamido-2,3,6-trideoxy-4-O-methoxymethyl-3-C-methyl-α-L-ribo-hexopyranoside (17), which was then converted in a straightforward manner into methyl 3-acetamido-2,3,6-trideoxy-3-C-methyl-α-L-ribo-hexopyranoside (20). Inversion of the configuration at C-4 of the latter compound, by means of an oxidation–reduction sequence, yielded methyl 3-acetamido-2,3,6-trideoxy-3-C-methyl-α-L-xylo-hexopyranoside (22), a derivative of the novel branched-chain amino sugar found in antibiotic A35512B.

An approach to branched-chain amino sugars, particularly derivatives of l-vancosamine (3-amino-2,3,6-trideoxy-3- C-methyl- l- lyxo-hexose) and its d enantiomer, via the cyanohydrin route

Methyl 4,6- O-benzylidene-2-deoxy-α- d- erythro-hexopyranosid-3-ulose reacted with potassium cyanide under equilibrating conditions to give, initially, methyl 4,6- O-benzylidene-3- C-cyano-2-deoxy-α- d- ribo-hexopyranoside ( 7), which, because it reverted slowly to the thermodynamically stable d- arabino isomer, could be crystallised directly from the reaction mixture. The mesylate derived from the kinetic product 7 could be converted by published procedures into methyl 3-acetamido-2,3,6-trideoxy-3- C-methyl-α- d- arabino-hexopyranoside, which was transformed into methyl N-acetyl-α- d-vancosaminide on inversion of the configuration at C-4. A related approach employing methyl 2,6-dideoxy-4- O-methoxymethyl-α- l- erythro-hexopyranosid-3-ulose gave the kinetic cyanohydrin and thence, via the spiro-aziridine 27, methyl 3-acetamido-2,3,6-trideoxy-3- C-methyl-α- l- arabino-hexopyranoside, a known precursor of methyl N-acetyl-α- l-vancosaminide.

A Novel Synthesis of a Branched-chain Amino Sugar, Methyl 2-Amino-2,3-dideoxy-3-C-formyl-α-d-xylofuranoside-3′R,5-hemiacetal

Abstract Methyl 2-amino-2N,3O-(o-benzenedisulfonyl)-2-deoxy-α-d-glucopyranoside, which was prepared from methyl 2-amino-2-deoxy-α-d-glucopyranoside and o-benzenedisulfonyl dichloride, was treated with sodium methoxide to afford exclusively a branched-chain amino sugar, methyl 2,3-dideoxy-3-C-formyl-2-(o-sulfobenzenesulfonyl)amino-α-d-xylofuranoside-3′R,5-hemiacetal sodium salt (6). Some derivatives were synthesized from 6.

The synthesis of derivatives of 3-amino-2,3,6-trideoxy-3-C-methyl-l-xylo-hexopyranose, the novel branched-chain amino sugar of antibiotic A35512B

The synthesis of derivatives of 3-amino-2,3,6-trideoxy-3-C-methyl-l-xylo-hexopyranose, the novel branched-chain amino sugar of antibiotic A35512B

ChemInform Abstract: ISOLATION AND STRUCTURE OF THE NOVEL BRANCHED‐CHAIN AMINO SUGAR DERIVED FROM ANTIBIOTIC A35512B

Chemischer InformationsdienstVolume 12, Issue 21 Natural Products ChemInform Abstract: ISOLATION AND STRUCTURE OF THE NOVEL BRANCHED-CHAIN AMINO SUGAR DERIVED FROM ANTIBIOTIC A35512B M. DEBONO, M. DEBONOSearch for more papers by this authorR. M. MOLLOY, R. M. MOLLOYSearch for more papers by this author M. DEBONO, M. DEBONOSearch for more papers by this authorR. M. MOLLOY, R. M. MOLLOYSearch for more papers by this author First published: May 26, 1981 https://doi.org/10.1002/chin.198121343Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume12, Issue21May 26, 1981 RelatedInformation

Isolation and structure of the novel branched-chain amino sugar derived from antibiotic A35512B

Isolation and structure of the novel branched-chain amino sugar derived from antibiotic A35512B

Branched-Chain Deoxy Nitro and Amino Sugar Derivatives from Ketose

Abstract The nitromethane addition to 1,2-O-isopropylidene-5-O-trityl-α-d-erythro-pentofuranos-3-ulose (1) proceeded smoothly to give the corresponding branched-chain sugar (2), which on acetylation afforded (3) followed by elimination of acetic acid in presence of a base catalyst, resulted in the formation of the corresponding nitro olefin (4). The nitro olefin when subjected to borohydride reduction gave 5-O-acetyl-3-deoxy-1,2-O-isopropylidene-3-(nitromethyl)-α-d-ribofuranose (5), which on catalytic hydrogenation followed by acetylation yielded the 3-(acetamidomethyl)-5-O-acetyl-3-deoxy-1,2-O-isopropylidene-α-d-ribofuranose (6). By the study of the NMR spectra of 3-deoxy derivatives (5) and (6), their d-ribo configurations were established.

An approach to the synthesis of branched-chain amino sugars from c-methylene sugars

The reaction of 1,2:5,6-di- O-isopropylidene-3- C-methylene-α- D- ribo-hexofuranose ( 4) with mercuric azide in hot 50% aqueous tetrahydrofuran yielded, after reductive demercuration, 3-azido-3-deoxy-1,2:5,6-di- O-isopropylidene-3- C-methyl-α- D-glucofuranose ( 5). Partial, acid hydrolysis of 5 afforded the diol 7, which gave 3-azido-3-deoxy-1,2- O-isopropylidene-5,6-di- O-methanesulphonyl-3- C-methyl-α- D-glucofuranose ( 8) on sulphonylation. On hydrogenation over a platinum catalyst and N-acetylation, the dimethanesulphonate 8 furnished 3,6-acetylepimino-3,6-dideoxy-1,2- O-isopropylidene-5- O-methanesulphonyl-3- C-methyl-α- D-glucofuranose ( 9), which was also prepared by an analogous sequence of reactions on 3-azido-3-deoxy-1,2- O-isopropylidene-5- O-methanesulphonyl-3- C-methyl-6- O-toluene- p-sulphonyl-α- D-glucofuranose ( 13). The formation of the N-acetylepimine 9 establishes the D- gluco configuration for 5. 1,2- O-Isopropylidene-3- C-methylene-α- D- ribo-hexofuranose ( 20) reacted with mercuric azide in aqueous tetrahydrofuran at ≈85° to give 3,6-anhydro-1,2- O-isopropylidene-3- C-methyl-α- D-glucofuranose ( 22) as a result of intramolecular participation by the C-6 hydroxyl group in the initial intermediate.

The synthesis of branched-chain amino sugars from C-methylene sugars: a re-assignment of structure

The synthesis of branched-chain amino sugars from C-methylene sugars: a re-assignment of structure

An approach to the synthesis of branched-chain amino sugars from C-methylene sugars

An approach to the synthesis of branched-chain amino sugars from C-methylene sugars