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14 pages, 1655 KiB

Open AccessArticle

Synthesis of Sucrose-Mimicking Disaccharide by Intramolecular Aglycone Delivery

by Kanae Sano, Akihiro Ishiwata, Hiroto Takamori, Takashi Kikuma, Katsunori Tanaka, Yukishige Ito and Yoichi Takeda

Molecules 2024, 29(8), 1771; https://doi.org/10.3390/molecules29081771 - 13 Apr 2024

Viewed by 585

Abstract

Rare sugars are known for their ability to suppress postprandial blood glucose levels. Therefore, oligosaccharides and disaccharides derived from rare sugars could potentially serve as functional sweeteners. A disaccharide [α-d-allopyranosyl-(1→2)-β-d-psicofuranoside] mimicking sucrose was synthesized from rare monosaccharides D-allose and [...] Read more.

Rare sugars are known for their ability to suppress postprandial blood glucose levels. Therefore, oligosaccharides and disaccharides derived from rare sugars could potentially serve as functional sweeteners. A disaccharide [α-d-allopyranosyl-(1→2)-β-d-psicofuranoside] mimicking sucrose was synthesized from rare monosaccharides D-allose and D-psicose. Glycosylation using the intermolecular aglycon delivery (IAD) method was employed to selectively form 1,2-cis α-glycosidic linkages of the allopyranose residues. Moreover, β-selective psicofuranosylation was performed using a psicofuranosyl acceptor with 1,3,4,6-tetra-O-benzoyl groups. This is the first report on the synthesis of non-reducing disaccharides comprising only rare d-sugars by IAD using protected ketose as a unique acceptor; additionally, this approach is expected to be applicable to the synthesis of functional sweeteners. Full article

(This article belongs to the Special Issue Carbohydrate Chemistry II)

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13 pages, 3043 KiB

Open AccessArticle

Biocatalytic Synthesis of Coumarin S-Glycosides: Towards Non-Cytotoxic Probes for Biomedical Imaging and Sensing

by Nastassja Burrini, Arnaud Pâris, Guillaume Collet, Pierre Lafite and Richard Daniellou

Molecules 2024, 29(6), 1322; https://doi.org/10.3390/molecules29061322 - 16 Mar 2024

Viewed by 1047

Abstract

This study unveils an innovative method for synthesizing coumarin S-glycosides, employing original biocatalysts able to graft diverse carbohydrate structures onto 7-mercapto-4-methyl-coumarin in one-pot reactions. The fluorescence properties of the generated thio-derivatives were assessed, providing valuable insights into their potential applications in biological [...] Read more.

This study unveils an innovative method for synthesizing coumarin S-glycosides, employing original biocatalysts able to graft diverse carbohydrate structures onto 7-mercapto-4-methyl-coumarin in one-pot reactions. The fluorescence properties of the generated thio-derivatives were assessed, providing valuable insights into their potential applications in biological imaging or sensing. In addition, the synthesized compounds exhibited no cytotoxicity across various human cell lines. This research presents a promising avenue for the development of coumarin S-glycosides, paving the way for their application in diverse biomedical research areas. Full article

(This article belongs to the Special Issue Carbohydrate Chemistry II)

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11 pages, 776 KiB

Open AccessArticle

Synthesis of Pseudooligosaccharides Related to the Capsular Phosphoglycan of Haemophilus influenzae Type a

by Anastasia A. Kamneva, Dmitry V. Yashunsky, Elena A. Khatuntseva and Nikolay E. Nifantiev

Molecules 2023, 28(15), 5688; https://doi.org/10.3390/molecules28155688 - 27 Jul 2023

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Abstract

Synthesis of spacer-armed pseudodi-, pseudotetra-, and pseudohexasaccharides related to the capsular phosphoglycan of Haemophilus influenzae type a, the second most virulent serotype of H. influenzae (after type b), was performed for the first time via iterative chain elongation using H-phosphonate chemistry [...] Read more.

Synthesis of spacer-armed pseudodi-, pseudotetra-, and pseudohexasaccharides related to the capsular phosphoglycan of Haemophilus influenzae type a, the second most virulent serotype of H. influenzae (after type b), was performed for the first time via iterative chain elongation using H-phosphonate chemistry for the formation of inter-unit phosphodiester bridges. These compounds were prepared for the design of neoglycoconjugates, as exemplified by the transformation of the obtained pseudohexasaccharide derivative into a biotinylated glycoconjugate suitable for use in immunological studies, particularly in diagnostic screening systems as a coating antigen for streptavidin-coated plates and chip slides. Full article

(This article belongs to the Special Issue Carbohydrate Chemistry II)

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17 pages, 4332 KiB

Open AccessArticle

Identification of New L-Fucosyl and L-Galactosyl Amides as Glycomimetic Ligands of TNF Lectin Domain of BC2L-C from Burkholderia cenocepacia

by Sarah Mazzotta, Giulia Antonini, Francesca Vasile, Emilie Gillon, Jon Lundstrøm, Annabelle Varrot, Laura Belvisi and Anna Bernardi

Molecules 2023, 28(3), 1494; https://doi.org/10.3390/molecules28031494 - 3 Feb 2023

Cited by 1 | Viewed by 1713

Abstract

The inhibition of carbohydrate-lectin interactions is being explored as an efficient approach to anti adhesion therapy and biofilm destabilization, two alternative antimicrobial strategies that are being explored against resistant pathogens. BC2L-C is a new type of lectin from Burkholderia cenocepacia that binds (mammalian) fucosides [...] Read more.

The inhibition of carbohydrate-lectin interactions is being explored as an efficient approach to anti adhesion therapy and biofilm destabilization, two alternative antimicrobial strategies that are being explored against resistant pathogens. BC2L-C is a new type of lectin from Burkholderia cenocepacia that binds (mammalian) fucosides at the N-terminal domain and (bacterial) mannosides at the C-terminal domain. This double carbohydrate specificity allows the lectin to crosslink host cells and bacterial cells. We have recently reported the design and generation of the first glycomimetic antagonists of BC2L-C, β-C- or β-N-fucosides that target the fucose-specific N-terminal domain (BC2L-C-Nt). The low water solubility of the designed N-fucosides prevented a full examination of this promising series of ligands. In this work, we describe the synthesis and biophysical evaluation of new L-fucosyl and L-galactosyl amides, designed to be water soluble and to interact with BC2L-C-Nt. The protein–ligand interaction was investigated by Saturation Transfer Difference NMR, Isothermal Titration Calorimetry and crystallographic studies. STD-NMR experiments showed that both fucosyl and galactosyl amides compete with α-methyl fucoside for lectin binding. A new hit compound was identified with good water solubility and an affinity for BC2L-C-Nt of 159 μM (ITC), which represents a one order of magnitude gain over α-methyl fucoside. The x-ray structure of its complex with BC2L-C-Nt was solved at 1.55 Å resolution. Full article

(This article belongs to the Special Issue Carbohydrate Chemistry II)

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14 pages, 982 KiB

Open AccessArticle

Investigation of the Protection of the C4 Hydroxyl Group in Macrobicyclic Kdo Donors

by Shogo Hamajima, Naoko Komura, Hide-Nori Tanaka, Akihiro Imamura, Hideharu Ishida, Tsuyoshi Ichiyanagi and Hiromune Ando

Molecules 2023, 28(1), 102; https://doi.org/10.3390/molecules28010102 - 23 Dec 2022

Cited by 6 | Viewed by 1395

Abstract

Chemical synthesis of 3-deoxy-d-manno-2-octulosonic acid (Kdo)-containing glycans, such as bacterial lipopolysaccharides (LPSs) and capsular polysaccharides (CPSs), is in high demand for the development of vaccines against pathogenic bacteria. We have recently achieved the complete α-stereoselective glycosidation of Kdo using a macrobicyclic [...] Read more.

Chemical synthesis of 3-deoxy-d-manno-2-octulosonic acid (Kdo)-containing glycans, such as bacterial lipopolysaccharides (LPSs) and capsular polysaccharides (CPSs), is in high demand for the development of vaccines against pathogenic bacteria. We have recently achieved the complete α-stereoselective glycosidation of Kdo using a macrobicyclic donor tethered at the C1 and C5 positions. In this study, to expand the scope of Kdo glycosidation, we sought to protect the 4-OH group, thereby shortening the reaction time and ensuring the conversion of the glycosyl acceptor via its selective removal. The protection of the 4-OH group influenced the reactivity of the Kdo donor, and the triisopropylsilyl (TIPS) group acted as a selectively removable booster. The 4-O-TIPS donor allowed the synthesis of the α(2,4)-linked dimeric Kdo sequence, which is widely found in bacterial LPSs. Full article

(This article belongs to the Special Issue Carbohydrate Chemistry II)

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13 pages, 5837 KiB

Open AccessArticle

Activation of Thioglycosides with Copper(II) Bromide

by Faranak Pooladian, Samira Escopy and Alexei V. Demchenko

Molecules 2022, 27(21), 7354; https://doi.org/10.3390/molecules27217354 - 29 Oct 2022

Cited by 2 | Viewed by 1730

Abstract

Reported herein is a new protocol for glycosidation of alkyl and aryl thioglycosides in the presence of copper(II) bromide. While the activation with CuBr₂ alone was proven suitable for reactive glycosyl donors, the activation of less reactive donors was more efficient in [...] Read more.

Reported herein is a new protocol for glycosidation of alkyl and aryl thioglycosides in the presence of copper(II) bromide. While the activation with CuBr₂ alone was proven suitable for reactive glycosyl donors, the activation of less reactive donors was more efficient in the presence of triflic acid as an additive. A variety of thioglycoside donors in reactions with different glycosyl acceptors were investigated to determine the initial scope of this reaction. Full article

(This article belongs to the Special Issue Carbohydrate Chemistry II)

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35 pages, 5378 KiB

Open AccessArticle

Synthesis of Four Orthogonally Protected Rare l-Hexose Thioglycosides from d-Mannose by C-5 and C-4 Epimerization

by Fruzsina Demeter, Ilona Bereczki, Anikó Borbás and Mihály Herczeg

Molecules 2022, 27(11), 3422; https://doi.org/10.3390/molecules27113422 - 25 May 2022

Cited by 4 | Viewed by 2272

Abstract

l-Hexoses are important components of biologically relevant compounds and precursors of some therapeuticals. However, they typically cannot be obtained from natural sources and due to the complexity of their synthesis, their commercially available derivatives are also very expensive. Starting from one of [...] Read more.

l-Hexoses are important components of biologically relevant compounds and precursors of some therapeuticals. However, they typically cannot be obtained from natural sources and due to the complexity of their synthesis, their commercially available derivatives are also very expensive. Starting from one of the cheapest d-hexoses, d-mannose, using inexpensive and readily available chemicals, we developed a reaction pathway to obtain two orthogonally protected l-hexose thioglycoside derivatives, l-gulose and l-galactose, through the corresponding 5,6-unsaturated thioglycosides by C-5 epimerization. From these derivatives, the orthogonally protected thioglycosides of further two l-hexoses (l-allose and l-glucose) were synthesized by C-4 epimerization. The preparation of the key intermediates, the 5,6-unsaturated derivatives, was systematically studied using various protecting groups. By the method developed, we are able to produce highly functionalized l-gulose derivatives in 9 steps (total yields: 21–23%) and l-galactose derivatives in 12 steps (total yields: 6–8%) starting from d-mannose. Full article

(This article belongs to the Special Issue Carbohydrate Chemistry II)

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Review

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28 pages, 2171 KiB

Open AccessReview

Impact and Control of Sugar Size in Glycoconjugate Vaccines

by Giuseppe Stefanetti, Calman Alexander MacLennan and Francesca Micoli

Molecules 2022, 27(19), 6432; https://doi.org/10.3390/molecules27196432 - 29 Sep 2022

Cited by 4 | Viewed by 2099

Abstract

Glycoconjugate vaccines have contributed enormously to reducing and controlling encapsulated bacterial infections for over thirty years. Glycoconjugate vaccines are based on a carbohydrate antigen that is covalently linked to a carrier protein; this is necessary to cause T cell responses for optimal immunogenicity, [...] Read more.

Glycoconjugate vaccines have contributed enormously to reducing and controlling encapsulated bacterial infections for over thirty years. Glycoconjugate vaccines are based on a carbohydrate antigen that is covalently linked to a carrier protein; this is necessary to cause T cell responses for optimal immunogenicity, and to protect young children. Many interdependent parameters affect the immunogenicity of glycoconjugate vaccines, including the size of the saccharide antigen. Here, we examine and discuss the impact of glycan chain length on the efficacy of glycoconjugate vaccines and report the methods employed to size polysaccharide antigens, while highlighting the underlying reaction mechanisms. A better understanding of the impact of key parameters on the immunogenicity of glycoconjugates is critical to developing a new generation of highly effective vaccines. Full article

(This article belongs to the Special Issue Carbohydrate Chemistry II)

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