An antimetastatic tetrasaccharide β-D-Gal-（1 → 4）-β-D- GlcpNAc-（1 →6）-α-D-Manp-（1 → 6）-β-D-Manp-OMe, was syn- thesized with two approaches. The first approach was a conventional method employing thioglyc...An antimetastatic tetrasaccharide β-D-Gal-（1 → 4）-β-D- GlcpNAc-（1 →6）-α-D-Manp-（1 → 6）-β-D-Manp-OMe, was syn- thesized with two approaches. The first approach was a conventional method employing thioglycoside and Koenigs-Knorr glycosylation reaction in 24% overall yield. The second one was a novel route through the azidoiodo-glycosylation strategy by using 2-iodo-2-deoxylactosyl azide as the donor in 36% overall yield.展开更多
Synthesis of the protected tetrasaccharide II is reported as the key intermediate of tetrasaccharide from laminin that is an important glycoprotein on the basement membrane.
Pseudomonas aeruginosa is an opportunistic pathogen responsible for cystic fibrosis,bloodstream infections and hospital-acquired pneumonia.The O-antigen of lipopolysaccharide on the cell surface of P.aeruginosa has be...Pseudomonas aeruginosa is an opportunistic pathogen responsible for cystic fibrosis,bloodstream infections and hospital-acquired pneumonia.The O-antigen of lipopolysaccharide on the cell surface of P.aeruginosa has been identified as a promising target for the development of carbohydrate-based vaccines.In this study,we present the first total synthesis of the tetrasaccharide repeating unit of P.aeruginosa serotype 4 O-antigen using a linear[((1+1)+1)+1]glycosylation strategy.All rare amino sugars were synthesized from commercially available monosaccharides.The formation of 1,2-cis L-fucosamine glycosidic bonds was achieved with high efficiency and stereoselectivity by judicious choice of C3/C4-OH protecting groups of L-fucosamine.The N-phenyl trifluoroacetimidate glycosyl donors have proven to be more efficient than selenoglycoside or thioglycoside donors during glycosylation,particularly when coupling with the low-reactivity C3-OH group of the O4-Bz protected L-FucN3 acceptor.TBSOTf has demonstrated higher efficacy as a catalyst compared to TMSOTf for promoting glycosylation with less reactive acceptors.The synthetic tetrasaccharide repeating unit of P.aeruginosa serotype 4 O-antigen,which incorporates a pentyl amine linker at the reducing end,has been prepared for conjugation with carrier proteins or for utilization in microarray studies aimed at further immunological investigations.展开更多
Treponema is a Gram-negative anaerobic bacterium,among which the pathogenic Treponema can cause various diseases,such as venereal syphilis(Treponema pallidum),yaws(Treponema carateum),and oral diseases(Treponema denti...Treponema is a Gram-negative anaerobic bacterium,among which the pathogenic Treponema can cause various diseases,such as venereal syphilis(Treponema pallidum),yaws(Treponema carateum),and oral diseases(Treponema denticola and Treponema medium).Although different from conventional lipopolysaccharides,the extracellular glycoconjugate of Treponema may still be a potential antigen and provide a candidate for vaccine development.Hence,we completed the first chemical synthesis of Treponema medium ATCC 700293 tetrasaccharide precursor containing L-ornithine(L-Orn)and D-aspartic acid(D-Asp)derivatives.The efficiency of non-reducing end disaccharide formation has been improved by optimizing the assembly of the protecting groups in the donors and acceptors.Our[3+1]glycosylation strategy attempted to reduce the length of the acceptor to increase the nucleophilicity of the hydroxyl group,thereby improving the efficiency of synthesizing the target tetrasaccharide.The L-Orn derivative was introduced at the final stage due to its influence on the glycosylation stereospecificity and efficiency.Therefore,the successful introduction of two amino acid derivatives and the synthesis of a tetrasaccharide precursor with complex functional-group modifications have provided valuable insights for synthesizing other complex bacterial glycans.展开更多
The title compound stachyose （C24H42021）, a biologicaly active tetrasaccharide, was characterized by X-ray diffraction analysis. It crystallizes in the orthorhombic system, space group P21212 with C24H42021, a = 23....The title compound stachyose （C24H42021）, a biologicaly active tetrasaccharide, was characterized by X-ray diffraction analysis. It crystallizes in the orthorhombic system, space group P21212 with C24H42021, a = 23.8760（3）, b = 12.71028（I2）, c = 10.81279（11） A, V = 3281.36（6） A3, Z = 4, Dc= 1.511 g/cm3, Mr = 746.58, F（000） = 1576, and μ = 1.230 mm^-1. The final R = 0.0666 and wR = 0.1797 for 6298 observed reflections （I 〉 2σ（I））. The molecular crystal structure of stachyose shows absolute stereochemistry of fl-D-fructofuranosyl a-D-galactopyranosyl- （1→6）-a-D-galactopyranosyl-（1→6）-a-D-glucopyranoside. The molecule is composed of two a-D-galactoses, one a-D-glucose, and one r-D-fructose and sequentially linked as a-Gal （1 →6） a-Gal （1→6） a-Glc （1→2） fl-Fru. The title compound is stacked into a 3D layer structure through hydrogen bonds. NMR spectra data are also assigned. In the crystal packing, X-ray analysis indicates that there are two intramolecular and eleven intermolecular hydrogen bonds in this compound.展开更多
基金supported by the National Basic Research Program of China(973 program,No.2012CB822100)the National Natural Science Foundation of China(No.20972012)
文摘An antimetastatic tetrasaccharide β-D-Gal-（1 → 4）-β-D- GlcpNAc-（1 →6）-α-D-Manp-（1 → 6）-β-D-Manp-OMe, was syn- thesized with two approaches. The first approach was a conventional method employing thioglycoside and Koenigs-Knorr glycosylation reaction in 24% overall yield. The second one was a novel route through the azidoiodo-glycosylation strategy by using 2-iodo-2-deoxylactosyl azide as the donor in 36% overall yield.
文摘Synthesis of the protected tetrasaccharide II is reported as the key intermediate of tetrasaccharide from laminin that is an important glycoprotein on the basement membrane.
基金funded by the National Natural Science Foundation of China(22207042,22277042,22325803)the National Key R&D Program of China(2023YFC2308000)the Open Project of Key Laboratory of Carbohydrate Chemistry and Biotechnology(Jiangnan University),Ministry of Education(KLCCBKF202203).
文摘Pseudomonas aeruginosa is an opportunistic pathogen responsible for cystic fibrosis,bloodstream infections and hospital-acquired pneumonia.The O-antigen of lipopolysaccharide on the cell surface of P.aeruginosa has been identified as a promising target for the development of carbohydrate-based vaccines.In this study,we present the first total synthesis of the tetrasaccharide repeating unit of P.aeruginosa serotype 4 O-antigen using a linear[((1+1)+1)+1]glycosylation strategy.All rare amino sugars were synthesized from commercially available monosaccharides.The formation of 1,2-cis L-fucosamine glycosidic bonds was achieved with high efficiency and stereoselectivity by judicious choice of C3/C4-OH protecting groups of L-fucosamine.The N-phenyl trifluoroacetimidate glycosyl donors have proven to be more efficient than selenoglycoside or thioglycoside donors during glycosylation,particularly when coupling with the low-reactivity C3-OH group of the O4-Bz protected L-FucN3 acceptor.TBSOTf has demonstrated higher efficacy as a catalyst compared to TMSOTf for promoting glycosylation with less reactive acceptors.The synthetic tetrasaccharide repeating unit of P.aeruginosa serotype 4 O-antigen,which incorporates a pentyl amine linker at the reducing end,has been prepared for conjugation with carrier proteins or for utilization in microarray studies aimed at further immunological investigations.
基金the National Natural Science Foundation of China(22325803,22077052,22277042,22107037,22177041,22207042)the China Postdoctoral Science Foundation(2021M691279)the National Key R&D Program of China(2023YFC2308000).
文摘Treponema is a Gram-negative anaerobic bacterium,among which the pathogenic Treponema can cause various diseases,such as venereal syphilis(Treponema pallidum),yaws(Treponema carateum),and oral diseases(Treponema denticola and Treponema medium).Although different from conventional lipopolysaccharides,the extracellular glycoconjugate of Treponema may still be a potential antigen and provide a candidate for vaccine development.Hence,we completed the first chemical synthesis of Treponema medium ATCC 700293 tetrasaccharide precursor containing L-ornithine(L-Orn)and D-aspartic acid(D-Asp)derivatives.The efficiency of non-reducing end disaccharide formation has been improved by optimizing the assembly of the protecting groups in the donors and acceptors.Our[3+1]glycosylation strategy attempted to reduce the length of the acceptor to increase the nucleophilicity of the hydroxyl group,thereby improving the efficiency of synthesizing the target tetrasaccharide.The L-Orn derivative was introduced at the final stage due to its influence on the glycosylation stereospecificity and efficiency.Therefore,the successful introduction of two amino acid derivatives and the synthesis of a tetrasaccharide precursor with complex functional-group modifications have provided valuable insights for synthesizing other complex bacterial glycans.
基金Supported by the public welfare research special project in State Administration for Quality Supervision and Inspection and Quarantine(No.201210209)
文摘The title compound stachyose （C24H42021）, a biologicaly active tetrasaccharide, was characterized by X-ray diffraction analysis. It crystallizes in the orthorhombic system, space group P21212 with C24H42021, a = 23.8760（3）, b = 12.71028（I2）, c = 10.81279（11） A, V = 3281.36（6） A3, Z = 4, Dc= 1.511 g/cm3, Mr = 746.58, F（000） = 1576, and μ = 1.230 mm^-1. The final R = 0.0666 and wR = 0.1797 for 6298 observed reflections （I 〉 2σ（I））. The molecular crystal structure of stachyose shows absolute stereochemistry of fl-D-fructofuranosyl a-D-galactopyranosyl- （1→6）-a-D-galactopyranosyl-（1→6）-a-D-glucopyranoside. The molecule is composed of two a-D-galactoses, one a-D-glucose, and one r-D-fructose and sequentially linked as a-Gal （1 →6） a-Gal （1→6） a-Glc （1→2） fl-Fru. The title compound is stacked into a 3D layer structure through hydrogen bonds. NMR spectra data are also assigned. In the crystal packing, X-ray analysis indicates that there are two intramolecular and eleven intermolecular hydrogen bonds in this compound.
