- Synthesis of C-Oligosaccharides through Versatile C(sp3)?H Glycosylation of Glycosides
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C-oligosaccharides are pharmacologically relevant because they are more hydrolysis-resistant than O-oligosaccharides. Despite indisputable advances, C-oligosaccharides continue to be underdeveloped, likely due to a lack of efficient and selective strategies for the assembly of the interglycosidic C?C linkages. In contrast, we, herein, report a versatile and robust strategy for the synthesis of structurally complex C-oligosaccharides via catalyzed C(sp3)?H activations. Thus, a wealth of complex interglycosidic (2→1)- and (1→1)-C-oligosaccharides becomes readily available by palladium-catalyzed C(sp3)?H glycoside glycosylation. The isolation of key palladacycle intermediates and experiments with isotopically-labeled compounds identified a trans-stereoselectivity for the C(sp3)?H glycosylation. The glycoside C(sp3)?H activation manifold was likewise exploited for the diversification of furanoses, pyranoses and disaccharides.
- Ackermann, Lutz,Kopp, Adelina,Wu, Jun
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- 2-nitroglycal and efficient synthesis method thereof
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The invention discloses an efficient synthesis method of 2-nitroglycal, and belongs to the technical field of synthesis of sugar. The structure of the 2-nitroglycal is shown in the specification. Secondly, the invention also provides a preparation method of the 2-nitro saccharide alkene, and the preparation method provided by the invention can be used for efficiently preparing the 2-nitroglycal through one-step synthesis.
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Paragraph 0075; 0077
(2021/08/06)
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- From 1,4-Disaccharide to 1,3-Glycosyl Carbasugar: Synthesis of a Bespoke Inhibitor of Family GH99 Endo-α-mannosidase
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Understanding the enzyme reaction mechanism can lead to the design of enzyme inhibitors. A Claisen rearrangement was used to allow conversion of an α-1,4-disaccharide into an α-1,3-linked glycosyl carbasugar to target the endo-α-mannosidase from the GH99 glycosidase family, which, unusually, is believed to act through a 1,2-anhydrosugar "epoxide" intermediate. Using NMR and X-ray crystallography, it is shown that glucosyl carbasugar α-aziridines can act as reasonably potent endo-α-mannosidase inhibitors, likely by virtue of their shape mimicry and the interactions of the aziridine nitrogen with the conserved catalytic acid/base of the enzyme active site.
- Lu, Dan,Zhu, Sha,Sobala, Lukasz F.,Bernardo-Seisdedos, Ganeko,Millet, Oscar,Zhang, Yongmin,Jiménez-Barbero, Jesus,Davies, Gideon J.,Sollogoub, Matthieu
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supporting information
p. 7488 - 7492
(2019/01/03)
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- Synthesis of 2-deoxy-2,2-difluoro-α-maltosyl fluoride and its X-ray structure in complex with Streptomyces coelicolor GlgEI-V279S
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Streptomyces coelicolor (Sco) GlgEI is a glycoside hydrolase involved in α-glucan biosynthesis and can be used as a model enzyme for structure-based inhibitor design targeting Mycobacterium tuberculosis (Mtb) GlgE. The latter is a genetically validated drug target for the development of anti-Tuberculosis (TB) treatments. Inhibition of Mtb GlgE results in a lethal buildup of the GlgE substrate maltose-1-phosphate (M1P). However, Mtb GlgE is difficult to crystallize and affords lower resolution X-ray structures. Sco GlgEI-V279S on the other hand crystallizes readily, produces high resolution X-ray data, and has active site topology identical to Mtb GlgE. We report the X-ray structure of Sco GlgEI-V279S in complex with 2-deoxy-2,2-difluoro-α-maltosyl fluoride (α-MTF, 5) at 2.3 ? resolution. α-MTF was designed as a non-hydrolysable mimic of M1P to probe the active site of GlgE1 prior to covalent bond formation without disruption of catalytic residues. The α-MTF complex revealed hydrogen bonding between Glu423 and the C1F which provides evidence that Glu423 functions as proton donor during catalysis. Further, hydrogen bonding between Arg392 and the axial C2 difluoromethylene moiety of α-MTF was observed suggesting that the C2 position tolerates substitution with hydrogen bond acceptors. The key step in the synthesis of α-MDF was transformation of peracetylated 2-fluoro-maltal 1 into peracetylated 2,2-difluoro-α-maltosyl fluoride 2 in a single step via the use of Selectfluor.
- Thanna, Sandeep,Lindenberger, Jared J.,Gaitonde, Vishwanath V.,Ronning, Donald R.,Sucheck, Steven J.
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supporting information
p. 7542 - 7550
(2015/07/15)
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- Synthesis of 2-deoxy-2,2-difluoro-α-maltosyl fluoride and its X-ray structure in complex with Streptomyces coelicolor GlgEI-V279S
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Streptomyces coelicolor (Sco) GlgEI is a glycoside hydrolase involved in α-glucan biosynthesis and can be used as a model enzyme for structure-based inhibitor design targeting Mycobacterium tuberculosis (Mtb) GlgE. The latter is a genetically validated drug target for the development of anti-Tuberculosis (TB) treatments. Inhibition of Mtb GlgE results in a lethal buildup of the GlgE substrate maltose-1-phosphate (M1P). However, Mtb GlgE is difficult to crystallize and affords lower resolution X-ray structures. Sco GlgEI-V279S on the other hand crystallizes readily, produces high resolution X-ray data, and has active site topology identical to Mtb GlgE. We report the X-ray structure of Sco GlgEI-V279S in complex with 2-deoxy-2,2-difluoro-α-maltosyl fluoride (α-MTF, 5) at 2.3 ? resolution. α-MTF was designed as a non-hydrolysable mimic of M1P to probe the active site of GlgE1 prior to covalent bond formation without disruption of catalytic residues. The α-MTF complex revealed hydrogen bonding between Glu423 and the C1F which provides evidence that Glu423 functions as proton donor during catalysis. Further, hydrogen bonding between Arg392 and the axial C2 difluoromethylene moiety of α-MTF was observed suggesting that the C2 position tolerates substitution with hydrogen bond acceptors. The key step in the synthesis of α-MDF was transformation of peracetylated 2-fluoro-maltal 1 into peracetylated 2,2-difluoro-α-maltosyl fluoride 2 in a single step via the use of Selectfluor.
- Thanna, Sandeep,Lindenberger, Jared J.,Gaitonde, Vishwanath V.,Ronning, Donald R.,Sucheck, Steven J.
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supporting information
p. 7542 - 7550
(2015/11/27)
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- Synthesis of fluorinated maltose derivatives for monitoring protein interaction by 19F NMR
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A novel reporter system, which is applicable to the 19F NMR investigation of protein interactions, is presented. This approach uses 2-F-labeled maltose as a spy ligand to indirectly probe protein-ligand or protein-protein interactions of proteins fused or tagged to the maltose-binding protein (MBP). The key feature is the simultaneous NMR observation of both 19F NMR signals of gluco/ manno-type-2-F-maltose-isomers; one isomer (α-gluco-type) binds to MBP and senses the protein interaction, and the nonbinding isomers (β-gluco- and/or α/β-manno-type) are utilized as internal references. Moreover, this reporter system was used for relative affinity studies of fluorinated and nonfluorinated carbohydrates to the maltose-binding protein, which were found to be in perfect agreement with published X-ray data. The results of the NMR competition experiments together with the established correlation between 19F chemical shift data and molecular interaction patterns, suggest valuable applications for studies of protein-ligand interaction interfaces.
- Braitsch, Michaela,Kaehlig, Hanspeter,Kontaxis, Georg,Fischer, Michael,Kawada, Toshinari,Konrat, Robert,Schmid, Walther
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supporting information; experimental part
p. 448 - 455
(2012/06/30)
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- A rapid synthesis of pyranoid glycals promoted by β-cyclodextrin and ultrasound
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A convenient and environmentally benign procedure for the synthesis of glycals from glycosyl bromides with very low zinc dust loading (1.5 equiv.) is described. The process is activated by β-cyclodextrin and ultrasound. Based on 19 samples, this method has been demonstrated to be highly effective for a broad range of glycosyl bromides, including acid- or base-sensitive and disaccharide glycosyl bromides. A yield of 85%-96% of glycals was obtained. Copyright
- Zhao, Jinzhong,Shao, Huawu,Wu, Xin,Shi, Shaojing
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experimental part
p. 1434 - 1440
(2011/11/05)
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- A mild and environmentally benign method for the synthesis of glycals in PEG-600/H2O
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Glycals were synthesized via a simple, mild, convenient and environmentally benign procedure, in which protected glycosyl bromides undergo the reductive elimination in the presence of zinc in PEG-600/H2O at room temperature. The glycals were obtained in 75-92% isolated yields.
- Zhao, Jinzhong,Wei, Shanqiao,Ma, Xiaofeng,Shao, Huawu
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experimental part
p. 1124 - 1127
(2010/05/02)
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- Versatile and mild synthesis of Di- and trisaccharidic 2-enopyranosyl cyanides by cyanation of per-O-acetylglycals with trimethylsilyl cyanide catalyzed by palladium(II) acetate
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A catalytic amount (1-2 mol%) of palladium(II) acetate was found to work as a catalyst for the cyanation of di- and trisaccharidic per-O-acetylglycals with trimethylsilyl cyanide to afford di- and trisaccharidic 2-enopyranosyl cyanides in high yields and in moderate stereoselectivities. Georg Thieme Verlag Stuttgart.
- Xu, Xiaoyong,Tan, Qitao,Hayashi, Masahiko
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p. 770 - 776
(2008/09/21)
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- Mild synthesis of disaccharidic 2,3-enopyranosyl cyanides and 2-C-2-deoxy pyranosyl cyanides with Hg(CN)2/HgBr2/TMSCN
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Lewis acid-catalyzed dimerization of mono- and disaccharidic per-O-acetylated glycals gave di- and tetrasaccharidic O-acetylated C-glycosides, respectively. 2,3-Enopyranosyl cyanides were obtained from per-O-acetylated glycals by a new, mild anomeric SN′-acetoxy displacement with Hg(CN)2/HgBr2/TMSCN. Per-O-acetylated 2-C-2-deoxy-pyranoses were converted into pyranosyl cyanides by the same reagent. An unprecedented acetic acid elimination from dimers with D-galacto- and L-fuco-configurations accompanied the SN-displacement under those conditions. A new set of 1H NMR coupling constants for 2,3-enopyranosyl systems was used for configurational assignment of complicated tetrasaccharide mimics.
- Franz, Andreas H.,Wei, YiQiu,Samoshin, Vyacheslav V.,Gross, Paul H.
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p. 7662 - 7669
(2007/10/03)
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- Acetobromomaltose, a new source of carbohydrate radicals. EPR characterisation of maltosyl and 2-deoxymaltos-2-yl radicals and syntheses of tetrasaccharide-like mimics, maltal, 3-α-maltosyl propiononitrile, 1,5-anhydromaltitol and 2-deoxymaltopyranoside
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The acetoxy-protected maltosyl radical 1, obtained through bromine abstraction from acetobromomaltose (ABM), was studied by means of EPR spectroscopy. At room temperature, only the spectrum of 1 was observed, but at higher temperatures a second radical, t
- Alberti, Angelo,Bertini, Sabrina,Comoli, Maura,Guerrini, Marco,Mele, Andrea,Vismara, Elena
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p. 6291 - 6297
(2007/10/03)
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- Development of a catalytic cycle for the generation of C1-glycosyl carbanions with Cp2TiCl2: Application to glycal synthesis
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A catalytic cycle has been developed for the conversion of glycosyl halides to their corresponding glycals using Cp2TiCl2. This process can be effectively used with only 30% of the in situ generated single electron reducing agent in contrast to the 2 equivalents normally employed. (C) 2000 Published by Elsevier Science Ltd.
- Hansen,Daasbjerg,Skrydstrup
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p. 8645 - 8649
(2007/10/03)
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- A convenient synthesis of glycals employing in-situ generated Cp2TiCl
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Reductive elimination of acetylated glycosyl bromides to the corresponding glycal is easily achieved by mixing the bromide with Cp2TiCl2 and Mn in THF, and hence does not require the separate preparation of Cp2TiCl using glove-box techniques.
- Hansen, Thomas,Krintel, Sussie L.,Daasbjerg, Kim,Skrydstrup, Troels
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p. 6087 - 6090
(2007/10/03)
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- A convenient, highly efficient one-pot preparation of peracetylated glycals from reducing sugars
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A convenient, highly efficient, one-pot, three-step procedure has been developed for the synthesis of peracetylated glycal derivatives from various reducing sugars including D-glucose, D-galactose, L-rhamnose, L-arabinose, D-maltose, D-lactose, and maltotriose. This procedure involves peracetylation of the reducing sugars with acetic anhydride and HBr/acetic acid followed by the transformation of the anomeric acetates to the corresponding bromides with additional HBr/acetic acid and finally reductive elimination of the 1-bromo and 2-acetoxy groups with Zn/CuSC4·5H2O in acetic acid/water containing sodium acetate. The overall yields of purified peracetylated glycals from the corresponding sugars range from 50 - 98%.
- Shull, Brian K.,Wu, Zhijun,Koreeda, Masato
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p. 955 - 964
(2007/10/03)
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