Applications of innovative synthetic strategies in anticancer drug Discovery: The Driving Force of new chemical reactions

Bioorganic & Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: 119, P. 130096 - 130096

Published: Jan. 9, 2025

Language: Английский

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Acceptor‐Reactivity‐Controlled Stereoconvergent Synthesis and Immunological Activity of a Unique Pentasaccharide from the Cell Wall Polysaccharide of Cutibacterium acnes C7

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(27)

Published: April 23, 2024

Bacterial cell-surface polysaccharides are involved in various biological processes and have attracted widespread attention as potential targets for developing carbohydrate-based drugs. However, the accessibility to structurally well-defined polysaccharide or related active oligosaccharide domains remains challenging. Herein, we describe an efficiently stereocontrolled approach first total synthesis of a unique pentasaccharide repeating unit containing four difficult-to-construct 1,2-cis-glycosidic linkages from cell wall Cutibacterium acnes C7. The features our include: 1) acceptor-reactivity-controlled glycosylation stereoselectively construct two challenging rare 1,2-cis-ManA2,3(NAc)

Language: Английский

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Gut microbiota in patients with sarcopenia: a systematic review and meta-analysis

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 22, 2025

Background Intestinal dysbiosis was considered a pivotal pathological mechanism underlying sarcopenia. Despite the fervor surrounding research in this domain, substantial controversy persists regarding obtained outcomes. Objective To systematically summarized disparities gut microbiota composition between group afflicted by sarcopenia and non-sarcopenia controls. Methods PubMed, Medline, CINAHL, EMBASE, Scopus, Web of Science Google Scholer, Cochrane Library gray literature sources were searched for randomized controlled trials. Meta-analysis random-effects meta-regression conducted using Rev. Man 5.3. Overall effect measured Hedges’s g determined Z-statistics. Cochran’s Q test I 2 used to investigate heterogeneity. The Newcastle-Ottawa Scale assess overall quality evidence. Results Ten studies, including 421 cases 1,642 controls, included meta-analysis. Patients with showed significantly reduced α diversity, β diversity different 8/9 studies. We also found more abundance phylum Proteobacteria genus Escherichia-Shigella , less Firmicutes Faecalibacterium Prevotella 9 Blautia group. Conclusion patients has undergone alterations, serving as fundamental reference further investigation into potential pathogenic mechanisms treatment strategies

Language: Английский

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Chemical synthesis elucidates the absolute configuration and key antigenic epitope of Vibrio cholerae serotype O100 O-antigen

Science Advances, Journal Year: 2025, Volume and Issue: 11(17)

Published: April 25, 2025

The emergence of drug-resistant strains Vibrio cholerae , coupled with the current limitations oral vaccines, underscores urgent need for development new vaccines. O-antigen V. serotype O100 has emerged as a promising candidate vaccine development. To investigate absolute configuration 3,5-dihydroxyhexanoyl (dHh) and to evaluate structure-activity relationship trisaccharide repeating unit, we completed total synthesis four potential isomers, along 11 additional oligosaccharide fragments O-antigen. Stereoselective reduction was used dHh, efficient assembly dHh ( R )-3-hydroxybutanoyl Hb) achieved through post-glycosylation modification strategy. Through NMR analysis, assigned 3 S ,5 . Glycan microarray screening indicated that Hb is essential antigenicity nonreducing end disaccharide 59 may serve minimal antigenic epitope. These findings are an important step toward design semi-synthetic carbohydrate vaccines against

Language: Английский

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Chemical Synthesis of a Densely Functionalized Aminodisaccharide from Fusobacterium nucleatum ATCC 23726 O-Antigen

Organic Letters, Journal Year: 2024, Volume and Issue: 26(19), P. 4142 - 4146

Published: May 8, 2024

Fusobacterium nucleatum, a colorectal-cancer-associated oncomicrobe, can trigger or accelerate numerous pathologies. We report the first synthesis of conjugation-ready disaccharide containing six amino groups from F. nucleatum ATCC 23726 O-antigen. Rare 2,3-diamido-d-glucuronic acid amide and 2-acetamido-4-amino-d-fucose were synthesized d-glucosamine through configuration inversion, nucleophilic substitution, C6 oxidation, deoxygenation. A judicious choice protecting reaction conditions enabled selective installation N-acetyl, N-propanoyl, N-formyl, carboxamido groups.

Language: Английский

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Structure‐Based Design and Synthesis of Lipid A Derivatives to Modulate Cytokine Responses

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(32)

Published: April 8, 2024

Abstract Agonists of Toll like receptors (TLRs) have attracted interest as adjuvants and immune modulators. A crystal structure TLR4/MD2 with E. coli LPS indicates that the fatty acid at C‐2 lipid component induces dimerization two TLR4‐MD2 complexes, which in turn initiates cell signaling leading to production (pro)inflammatory cytokines. To probe importance ( R )‐3‐hydroxymyristate A, a range bis‐ mono‐phosphoryl derivatives different modifications were prepared by strategy 2‐methylnaphthyl ethers employed permanent protecting group could be readily removed catalytic hydrogenation. The amine was protected 9‐fluorenylmethyloxycarbamate, later stage give free modified acids. synthetic As induced same cytokines, however, large differences activity observed. compound having hexanoyl moiety still showed agonistic properties, but further shortening butanoyl abolished activity. had larger influence on monophosphoryl As. selectively antagonize TRIF associated cytokines or A.

Language: Английский

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Stereocontrolled Synthesis of a Heptose- and Kdo-Containing Common Inner-Core Trisaccharide of Lipopolysaccharides from Multiple Pathogenic Bacteria

Synlett, Journal Year: 2024, Volume and Issue: unknown

Published: April 6, 2024

Abstract Lipopolysaccharides (LPSs) are major virulence determinants in Gram-negative bacteria and responsible for many pathophysiological processes during bacterial infections. However, the accessibility of LPS-associated oligosaccharides infectious mechanism study vaccine development remains challenging. We report an efficient stereocontrolled approach synthesis a common inner-core trisaccharide containing difficult-to-access, rare, higher-carbon sugars: heptose (Hep) 3-deoxy-α-d-manno-oct-2-ulosonic acid (Kdo). Key features include comprehensive elaboration practical versatile Hep Kdo building blocks, stereoselective assembly from multiple pathogenic bacteria.

Language: Английский

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Acceptor‐Reactivity‐Controlled Stereoconvergent Synthesis and Immunological Activity of a Unique Pentasaccharide from the Cell Wall Polysaccharide of Cutibacterium acnes C7

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(27)

Published: April 23, 2024

Abstract Bacterial cell‐surface polysaccharides are involved in various biological processes and have attracted widespread attention as potential targets for developing carbohydrate‐based drugs. However, the accessibility to structurally well‐defined polysaccharide or related active oligosaccharide domains remains challenging. Herein, we describe an efficiently stereocontrolled approach first total synthesis of a unique pentasaccharide repeating unit containing four difficult‐to‐construct 1,2‐ cis ‐glycosidic linkages from cell wall Cutibacterium acnes C7. The features our include: 1) acceptor‐reactivity‐controlled glycosylation stereoselectively construct two challenging rare ‐ManA2,3(NAc) 2 (β‐2,3‐diacetamido‐2,3‐dideoxymannuronic acid) linkages, 2) combination use 6‐ O ‐ tert ‐butyldiphenylsilyl (6‐ ‐TBDPS)‐mediated steric shielding effect ether solvent install ‐glucosidic linkage, 3) bulky 4,6‐di‐ ‐butylsilylene (DTBS)‐directed stereospecifically ‐galactosidic 4) stereoconvergent [2+2+1] one‐pot chemoselective rapidly assemble target pentasaccharide. Immunological activity tests suggest that can induce production proinflammatory cytokine TNF‐α dose‐dependent manner.

Language: Английский

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Chemical Synthesis of a Disaccharide from Vibrio vulnificus Biotype 2 Serovar A O-Antigen Containing a Rare l-GalpNAmA

Synthesis, Journal Year: 2024, Volume and Issue: 56(19), P. 3009 - 3018

Published: June 7, 2024

Abstract The bacterium Vibrio vulnificus can cause severe infections internally and externally. mortality rate of V. vulnificus-associated gangrene septicemia has increased due to antibiotic resistance the absence human vaccine. Bacterial carbohydrates have been widely used in development bacterial vaccines. Here, a rare l-GalpNAmA-containing disaccharide that exists biotype 2 serovar A O-antigen was synthesized from d-glucose l-galactose. An investigation on influence different linkers synthetic efficiency indicated amine linker more practicality. Two α-glycosidic linkages were constructed with good stereoselectivity by using nonparticipating C2 azido group solvent effect. orthogonal protection strategy allowed introductions carboxyl acetamidino (Am) groups at stage. synthesis amine-linked will provide basis for preparation trisaccharide repeating unit longer fragments O-antigen, as well other complex glycans.

Language: Английский

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Chemical Synthesis of an Orthogonally Protected 5,7-Diamino-3,5,7,9-tetradeoxy-d-glycero-l-gluco-2-nonulosonic Acid from N-Acetylneuraminic Acid

Organic Letters, Journal Year: 2024, Volume and Issue: 26(24), P. 5215 - 5219

Published: June 11, 2024

Bacterial nonulosonic acids (NulOs), which feature a nine-carbon backbone, are associated with the biological functions of bacterial glycans. Here, an orthogonally protected 5-amino-7-azido-3,5,7,9-tetradeoxy-d-glycero-l-gluco-2-nonulosonic acid related to Fusobacterium nucleatum ATCC 23726 NulO was synthesized from N-acetylneuraminic sequential performance C5,7 azidation, C9 deoxygenation, C4 epimerization, and N5,7 differentiation. The C5 azido group in obtained 5,7-diazido-NulO can be regioselectively reduced differentiate two amino groups.

Language: Английский

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