Total Synthesis of Nona-decasaccharide Motif from Ganoderma sinense Polysaccharide Enabled by Modular and One-Pot Stereoselective Glycosylation Strategy

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(25), С. 17446 - 17455

Опубликована: Июнь 11, 2024

Polysaccharides from a medicinal fungus Ganoderma sinense represent important and adjunctive therapeutic agents for treating various diseases, including leucopenia hematopoietic injury. However, the synthetic accessibility to long, branched, complicated carbohydrates chains polysaccharides remains challenging task in chemical synthesis. Here, we report modular synthesis of nona-decasaccharide motif polysaccharide GSPB70-S with diverse biological activities first time through one-pot stereoselective glycosylation strategy on basis glycosyl ortho-(1-phenyvinyl)benzoates, which not only sped up but also reduced waste avoided aglycones transfer issues inherent thioglycosides. The route highlights following key steps: (1) preactivation-based highly constructions several 1,2-cis-glycosidic linkages, three α-d-GlcN-(1 → 4) linkages one α-d-Gal-(1 bond via reagent N-methyl-N-phenylformamide modulation; (2) orthogonal assembly 1,2-trans-glycosidic linear branched glycans fragments by strategic combinations N-phenyltrifluoroacetimidates, ortho-alkynylbenzoates, ortho-(1-phenyvinyl)benzoates; (3) final [1 × 4 + 15] Yu efficient target. Additionally, shorter sequences 4-mer, 5-mer, 6-mer are prepared structure–activity relationship studies. present work shows that this can offer reliable effective means streamline complex many bonds.

Язык: Английский

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Highly stereoselective α-glycosylation with GalN₃ donors enabled collective synthesis of mucin-related tumor associated carbohydrate antigens

Chemical Science, Год журнала: 2024, Номер 15(17), С. 6552 - 6561

Опубликована: Янв. 1, 2024

Collective synthesis of mucin-related tumor associated carbohydrate antigens has been achieved via this new α-glycosylation method with GalN 3 donors, which features mild conditions, broad substrate scope, high yields and stereoselectivities.

Язык: Английский

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Stereoselective α‐Glycosylation with GlcN₃ Donors Enabled Collective Syntheses of Acinetobacter baumannii Capsular Polysaccharides K43, K47 and K88 Repeating Units^†

Chinese Journal of Chemistry, Год журнала: 2024, Номер 42(14), С. 1593 - 1598

Опубликована: Март 13, 2024

Comprehensive Summary Collective syntheses of A. baumannii CPS K43, K47 and K88 repeating units have been accomplished via a new α‐glycosylation method with GlcN 3 as donors, which features: 1) mild reaction conditions, 2) good to high yields, 3) excellent stereoselectivities. The synthetic route also highlights an orthogonal one‐pot coupling strategy on the basis glycosyl ortho ‐(1‐phenylvinyl)benzoates for stereoselective constructions both 1,2‐ trans cis glycosidic bonds, precluding issues aglycone transfer.

Язык: Английский

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Precision Synthesis and Antiliver Fibrosis Activity of a Highly Branched Acidic 63-Mer Pectin Polysaccharide

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 25, 2025

Natural polysaccharides possess various biological functions and have become increasingly important as drug candidates for biomedical development. However, the accessibility to multiple-branched large-sized acidic with well-defined structures identification of related active glycan domains remain challenging. Here, we report precision synthesis a highly branched pectin polysaccharide up 63-mer containing 10 different glycosidic linkages from Lycium barbarum. The synthetic strategy relies on stereoselective modular assembly an orthogonally protected decasaccharide backbone, efficient three side chain glycans by integration stereocontrolled one-pot chemoselective glycosylations hydrogen-bond-mediated aglycone delivery approach, convergent target in site-specific glycosylation manner via flexible orthogonal protecting group manipulations. Structure–activity relationship studies its short fragments (9-mer, 10-mer, 11-mer, 33-mer) suggest that domain exhibits better antiliver fibrosis activity.

Язык: Английский

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Synthesis of Campylobacter jejuni capsular oligosaccharides and identification of a potential O -antigen against campylobacteriosis

Science Advances, Год журнала: 2025, Номер 11(15)

Опубликована: Апрель 9, 2025

The vaccines against campylobacteriosis are urgently needed because of the rising multidrug resistance pathogenic Campylobacter jejuni . capsular polysaccharides these bacteria, containing unique 6-deoxy-β- d - ido -heptopyranosyl or l glycero -β- residues, have emerged as attractive antigens. Expeditious assembly oligosaccharides derived from glycans is challenging β- -idopyranosidic linkages formidable to directly construct. Furthermore, whether synthetic C. could induce sufficient immunogenicity potential antigens remains unexplored. Here, we report a protocol for forming bonds using α- -6-deoxy- -heptopyranosyl, -idopyranosyl, and -/ -α- ortho -hexynylbenzoates glycosylating agents under gold(I) catalysis. To demonstrate versatility methods, concise synthesis conjugatable di-/tetra-/hexa-/octasaccharides, having backbone [→3)-6-deoxy-β- -heptopyranosyl-(1→4)-2-acetamido-2-deoxy-β- -glucopyranosyl-(1→], has been achieved. assessment glycoconjugates, prepared by conjugating synthesized cross-reactive material 197, reveals disaccharide O -antigen developing campylobacteriosis. This work should facilitate development infections.

Язык: Английский

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Comprehensive synthesis and anticoagulant evaluation of a diverse fucoidan library

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Май 10, 2025

Fucoidan, a sulfated glycan derived from brown algae, has garnered significant attention for its anticoagulant properties. However, the structural complexity and heterogeneity of naturally extracted fucoidan have hindered comprehensive understanding structure-activity relationship, limiting development fucoidan-based drugs. To address this challenge, we synthesize diverse library 58 distinct fucoidans with multiple contiguous 1,2-cis glycosidic bonds, ranging disaccharides to dodecasaccharides, using highly efficient preactivation-based one-pot glycosylation strategy. This includes compounds various sulfation patterns (2,3-O-di-, 3,4-O-di-, 2,3,4-O-tri-sulfation) encompassing nearly all possible structures. In vitro assays demonstrate that both molecular size degree play crucial roles in potency. Notably, 29, 30, 37, significantly prolong human plasma activated partial thromboplastin time (APTT), comparable effect enoxaparin, without affecting prothrombin (PT) or thrombin (TT). selective inhibition intrinsic coagulation pathway suggests reduced risk bleeding, highlighting therapeutic potential these as safer agents.

Язык: Английский

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Expeditious chemical synthesis of xylomannans disproves the proposed antifreeze activities

National Science Review, Год журнала: 2024, Номер 11(10)

Опубликована: Авг. 23, 2024

ABSTRACT Cold-adapted species are able to generate cryoprotective proteins and glycoproteins prevent freezing damage. The [→4)-β-D-Manp-(1→4)-β-D-Xylp-(1→]n xylomannan from the Alaska beetle Upis ceramboides was disclosed by Walters co-workers in 2009 as first glycan-based antifreeze agent, which later reported be found diverse taxa. Here, we report rapid synthesis of four types xylomannans, including proposed up a 64-mer (Type I), regioisomeric [→3)-β-D-Manp-(1→4)-β-D-Xylp-(1→]n 16-mer II), diastereomeric [→4)-β-L-Manp-(1→4)-β-D-Xylp-(1→]n III) block-wise [→4)-β-D-Manp-(1→]m[→4)-β-D-Xylp-(1→]n 32-mer IV), employing strategic iterative exponential glycan growth (IEGG) process. nuclear magnetic resonance spectral data alleged natural accordance only those Type IV none these synthetic xylomannans has been capable inducing thermal hysteresis. These results disprove previous reports about occurrence xylomannans.

Язык: Английский

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A Ligand-Controlled Approach Enabling Gold(I)-Catalyzed Stereoinvertive Glycosylation with Primal Glycosyl ortho-Alkynylbenzoate Donors

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Сен. 24, 2024

A diarylurea-containing phosphine ligand-modulated stereoinvertive

Язык: Английский

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One-Pot Assembly of Octasaccharide Motif from Cranberry Arabinoxyloglucan Oligosaccharides

Synlett, Год журнала: 2024, Номер unknown

Опубликована: Июнь 30, 2024

Abstract Chemical synthesis of octasaccharide motif from cranberry arabinoxyloglucan oligosaccharides with antiadhesion activities has been achieved for the first time. Synthetic approach highlights following features: 1) stereoselective constructions 1,2-cis-Xyl bonds via combination reagent modulation and remote participation; 2) modular [1+3+1+3] orthogonal one-pot assembly target on basis glycosyl ortho-(1-phenylvinyl)benzoate, which avoids issues such as aglycone transfer associated glycosylation based thioglycosides.

Язык: Английский

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ZnI2-Mediated cis-Glycosylations of Various Constrained Glycosyl Donors: Recent Advances in cis-Selective Glycosylations

Molecules, Год журнала: 2024, Номер 29(19), С. 4710 - 4710

Опубликована: Окт. 4, 2024

An efficient and versatile glycosylation methodology is crucial for the systematic synthesis of oligosaccharides glycoconjugates. A direct intermolecular an indirect intramolecular have been developed, former can be applied to medium-to-long-chain glycans like that nucleotides peptides. The development a generally applicable approach stereoselective construction glycosidic bonds remains major challenge, especially 1,2-

Язык: Английский

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