Orthogonal chemistry is a valuable tool in the preparation of complex molecules as heteroglycoclusters. Unfortunately, selective heteroconjugation of multifunctional starting materials remains a ...usually challenging problem to overcome. Herein, we report the first report on harnessing N‐alkylation of N‐acylhydrazone as a key step in the orthogonal synthesis. Sequentially associated with the azido‐alkyne click chemistry, it stands out as a new and straightforward synthetic method of glycoconjugate small molecules, heterodisaccharides, and heteroglycoclusters based on cone p‐tBu‐calix4arene and 1,3‐alt p‐tBu‐thiacalix4arene with potential drug‐like properties.
We report a new orthogonal strategy involving the N‐alkylation of N‐acylhydrazone as a key step. When followed by azido‐alkyne click chemistry, it represents a new and straightforward synthetic method to prepare N‐alkyl‐NAH glycoconjugates of small molecules, heterodisaccharides, and heteroglycoclusters‐based on cone p‐tBu‐calix4arene and 1,3‐alt p‐tBu‐thiacalix4arene with potential drug‐like properties.
When working on the synthesis of substituted cyclodextrins (CDs), the main challenge remains the analysis of the reaction media content. Our objective in this study was to fully characterise a ...complex isomers mixture of Lipidyl-βCDs (LipβCD) obtained with a degree of substitution 1 (DS = 1) from a one-step synthesis pathway. The benefit of tandem mass spectrometry (MS/MS) and ion mobility separation hyphenated with mass spectrometry (IM-MS) was investigated. The MS/MS fragment ion‘s relative intensities were analysed by principal component analysis (PCA) to discriminate isomers. The arrival time distribution (ATD) of each isomer was recorded using a travelling wave ion mobility (TWIM) cell allowing the determination of their respective experimental collision cross section (CCSexp). The comparison with the predicted theoretical CCS (CCSth) obtained from theoretical calculations propose a regioisomer assignment according to the βCD hydroxyl position (2, 3, or 6) involved in the reaction. These results were validated by extensive NMR structural analyses of pure isomers combined with molecular dynamics simulations. This innovative approach seems to be a promising tool to elucidate complex isomer mixtures such as substituted cyclodextrin derivatives.
A straightforward synthesis of heteroglycoclusters based p-t-butylcalix4arene has been achieved. The key step is the formation of hetero-halopentyloxy-p-t-butylcalix 4arene mixture via haloalkylation ...with 1-bromo-5-chloropentane as asymmetric alkylating reagent. Subsequent selective exchange of bromide by azide under mild conditions provides selectively azido-chloro species suitable for click reaction with first propargylglycoside. The products here can then be subjected to further azidation to enable attachment of different glycosides via click chemistry reaction. GRAPHICS .
A systematic study of the suitability of α,α′-dibromo-o-xylene as a reagent for cyclic o-xylylene protection of vic-diols in different monosaccharide substrates is reported. The installation of this ...protecting group, formally equivalent to a di-O-benzylation reaction, proceeds with good regioselectivity toward 1,2-trans-diequatorial diol systems in pyranose and furanose rings. Initially, the benzyl ether-type derivative of the more acidic hydroxyl is preferentially formed. Subsequent intramolecular etherification toward the equatorial-oriented vicinal OH is kinetically favored. The methodology has been implemented for the simultaneous protection of the secondary O-2 and O-3 positions of a single d-glucopyranosyl unit in cyclic oligosaccharides of the cyclodextrin (CD) family (cyclomaltohexa-, -hepta-, and -octaose; α, β, and γCD).
Summary
Sugars modulate many vital metabolic and developmental processes in plants, from seed germination to flowering, senescence and protection against diverse abiotic and biotic stresses. However, ...the exact mechanisms involved in morphogenesis, developmental signalling and stress tolerance remain largely unknown. Here we report the characterization of a novel Arabidopsis thaliana mutant, sweetie, with drastically altered morphogenesis, and a strongly modified carbohydrate metabolism leading to elevated levels of trehalose, trehalose‐6‐phosphate and starch. We additionally show that the disruption of SWEETIE causes significant growth and developmental alterations, such as severe dwarfism, lancet‐shaped leaves, early senescence and flower sterility. Genes implicated in sugar metabolism, senescence, ethylene biosynthesis and abiotic stress were found to be upregulated in sweetie. Our physiological, biochemical, genetic and molecular data indicate that the mutation in sweetie was nuclear, single and recessive. The effects of metabolizable sugars and osmolytes on sweetie morphogenesis were distinct; in light, sweetie was hypersensitive to sucrose and glucose during vegetative growth and a partial phenotypic reversion took place in the presence of high sorbitol concentrations. However, SWEETIE encodes a protein that is unrelated to any known enzyme involved in sugar metabolism. We suggest that SWEETIE plays an important regulatory function that influences multiple metabolic, hormonal and stress‐related pathways, leading to altered gene expression and pronounced changes in the accumulation of sugar, starch and ethylene.
•Three phospholipo-oligohyaluronates (HA-DP) were synthesized to prepare decorated liposomes.•The uptake of these HA-DP-liposomes is higher in lung cancer cell lines with high CD44 ...expression.•HA-DP-liposomes did not show cytotoxicity or inflammatory effects.
In this work hyaluronic acid (HA) oligosaccharides with degree of polymerization (DP) 4, 6 and 8, obtained by enzymatic depolymerization of HA, were conjugated to a PEG-phospholipid moiety. The products (HA-DP4, HA-DP6 and HA-DP8) were used to prepare decorated liposomes. The cellular uptake of HA-DP4, HA-DP6 and HA-DP8-decorated fluorescently labelled liposomes was significantly higher (12 to 14-fold) in lung cancer cell lines with high CD44 expression than in those with low CD44 expression, suggesting a receptor-mediated entry of HA-conjugated formulations. Competition assays showed that the uptake followed this rank order: HA-DP8>HA-DP6>HA-DP4 liposomes. Moreover, they are capable of a faster interaction with CD44, followed by phagocytosis, than HA liposomes obtained from HA of higher molecular weight (4800 and 14800 Da). HA-DP4, HA-DP6 and HA-DP8-liposomes did not show cytotoxicity or inflammatory effects. Overall, we propose our new HA-DP oligosaccharides as biocompatible and effective tools for a potential drug delivery to CD44-positive cells.
Heparan sulfate (HS), a glycosaminoglycan related to heparin, is a linear polysaccharide, consisting of repeating disaccharide units. This compound is involved in multiple biological processes such ...as inflammation, coagulation, angiogenesis and viral infections. Our work focuses on the synthesis of simple HS analogs for the study of structure-activity relationships, with the aim of modulating these biological activities. Thioglycoside analogs, in which the interglycosidic oxygen is replaced by a sulfur atom, are very interesting compounds in terms of therapeutic applications. Indeed, the thioglycosidic bond leads to an improvement of their stability and can allow the inhibition of enzymes involved in physiological and pathological processes. In our previous work, we developed a synthetic sequence which led to a non-sulfated thiodisaccharide analog of HS. In this paper, we report our results of the development of a new synthetic method allowing access to the novel sulfated
-disaccharide, as well as to their oxygenated analogues (
-disaccharide and sulfated
-disaccharide). These 4 compounds were also tested for the inhibition of heparanase, an enzyme involved in biological processes like tumor growth and inflammation. The obtained IC
values in the micromolar range showed the impact of the interglycosidic sulfur atom and the 6-sulfate group.
•Acid treatments of juice wastes led to three families of oligogalacturonic acids.•A medium size oligosaccharide family was easily obtained by ethanol precipitation.•HPAEC, MALDI-MS and SEC-MS were ...used for complete characterization of OGAs families.•These defined fractions are useful to identify the active species for elicitation.
Pectin oligosaccharides, which can be obtained from fruit wastes, have proven their potential as plant immune-system elicitors. Although the precise size of active species is still under investigation, medium size oligosaccharides have been reported as the most active. Three defined oligogalacturonic acid (OGAs) mixtures were produced from commercial pectin, orange peel and apple pomace residues. The methodology developed involves two sequential acid treatments followed by stepwise ethanol precipitation. Without the need of chromatographic separations, three different fractions were obtained. The fractions were analyzed by high performance anion exchange chromatography (HPAEC) and were completely characterized by mass spectrometry, showing that the small size, medium size and large size fractions contained OGAs of degree of polymerization 3 to 9, 6 to 18, and 16 to 55, respectively.
Sulfated oligosaccharides are involved in important biological events that are often modulated by specific sequences and sulfation patterns, but their structural analysis remains challenging. ...Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) analysis of three different sulfated oligosaccharides (Fondaparinux, the octasulfated pentasaccharide, a disulfated heparin-derived tetrasaccharide 1, and an octasulfated maltoheptaose) 2 was performed using the 2-(4-hydroxyphenylazo)benzoic acid-tetramethylguanidinium (HABA-TMG2) matrix. High resolution mass spectrometry of the main ions observed was successful, and this was complemented by tandem mass spectrometry (MS/MS) analysis for structural assessment. Despite sulfate losses, fully sulfated molecular ions were observed and these allowed the determination of oligosaccharide structures: UA-GlcNAc-UA(2S)-AnhMan(6S) for compound 1 and (Glc6S)6-Glc (1S,6S) for compound 2.
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