- Discovery of Salidroside-Derivated Glycoside Analogues as Novel Angiogenesis Agents to Treat Diabetic Hind Limb Ischemia
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Therapeutic angiogenesis is a potential therapeutic strategy for hind limb ischemia (HLI); however, currently, there are no small-molecule drugs capable of inducing it at the clinical level. Activating the hypoxia-inducible factor-1 (HIF-1) pathway in skeletal muscle induces the secretion of angiogenic factors and thus is an attractive therapeutic angiogenesis strategy. Using salidroside, a natural glycosidic compound as a lead, we performed a structure-activity relationship (SAR) study for developing a more effective and druggable angiogenesis agent. We found a novel glycoside scaffold compound (C-30) with better efficacy than salidroside in enhancing the accumulation of the HIF-1α protein and stimulating the paracrine functions of skeletal muscle cells. This in turn significantly increased the angiogenic potential of vascular endothelial and smooth muscle cells and, subsequently, induced the formation of mature, functional blood vessels in diabetic and nondiabetic HLI mice. Together, this study offers a novel, promising small-molecule-based therapeutic strategy for treating HLI.
- Liu, Caiping,Han, Jingxuan,Marcelina, Olivia,Nugrahaningrum, Dyah Ari,Huang, Song,Zou, Meijuan,Wang, Guixue,Miyagishi, Makoto,He, Yun,Wu, Shourong,Kasim, Vivi
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supporting information
p. 135 - 162
(2022/01/14)
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- Streamlined access to carbohydrate building blocks: Methyl 2,4,6-tri-O-benzyl-α-D-glucopyranoside
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Presented herein is an improved synthesis of a common 3-OH glycosyl acceptor. This compound is a building block that is routinely synthesized by many research groups to be used in glycosylation refinement studies. The only known direct synthesis by Koto lacks regioselectivity and relies on chromatography separation using hazardous solvents. Our improved synthetic approach relies on Koto's selective benzylation protocol, but it is followed by acylation-purification-deacylation sequence. Although this approach involves additional manipulations, it provides consistent results and is superior to other indirect strategies. Also obtained, albeit in minor quantities, is 4-OH acceptor, another common building block.
- Demchenko, Alexei V.,Kashiwagi, Gustavo A.,Shrestha, Ganesh,Stine, Keith J.
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- Tuning the activity of iminosugars: novel N-alkylated deoxynojirimycin derivatives as strong BuChE inhibitors
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We have designed unprecedented cholinesterase inhibitors based on 1-deoxynojirimycin as potential anti-Alzheimer’s agents. Compounds are comprised of three key structural motifs: the iminosugar, for interaction with cholinesterase catalytic anionic site (
- Ahuja-Casarín, Ana I.,Merino-Montiel, Penélope,Vega-Baez, José Luis,Montiel-Smith, Sara,Fernandes, Miguel X.,Lagunes, Irene,Maya, Inés,Padrón, José M.,López, óscar,Fernández-Bola?os, José G.
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p. 138 - 146
(2020/11/27)
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- Highly regioselective and stereoselective synthesis of C-Aryl glycosidesvianickel-catalyzedortho-C-H glycosylation of 8-aminoquinoline benzamides
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C-Aryl glycosides are of high value as drug candidates. Here a novel and cost-effective nickel catalyzedortho-CAr-H glycosylation reaction with high regioselectivity and excellent α-selectivity is described. This method shows great functional group compatibility with various glycosides, showing its synthetic potential. Mechanistic studies indicate that C-H activation could be the rate-determining step.
- Chen, Xi,Ding, Ya-Nan,Gou, Xue-Ya,Liang, Yong-Min,Luan, Yu-Yong,Niu, Zhi-Jie,Shi, Wei-Yu,Zhang, Zhe,Zheng, Nian
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supporting information
p. 8945 - 8948
(2021/09/10)
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- Design, synthesis, and biological evaluation of desmuramyl dipeptides modified by adamantyl-1,2,3-triazole
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Muramyl dipeptide (MDP) is the smallest peptidoglycan fragment able to trigger the immune response. Structural modification of MDP can lead to the preparation of analogs with improved immunostimulant properties, including desmuramyl peptides (DMPs). The aim of this work was to prepare the desmuramyl peptide (L-Ala-D-Glu)-containing adamantyl-triazole moiety and its mannosylated derivative in order to study their immunomodulatory activities in vivo. The adjuvant activity of the prepared compounds was evaluated in a murine model using ovalbumin as an antigen, and compared to the reference adjuvant ManAdDMP. The results showed that the introduction of the lipophilic adamantyl-triazole moiety at the C-terminus of L-Ala-D-Glu contributes to the immunostimulant activity of DMP, and that mannosylation of DMP modified with adamantyl-triazole causes the amplification of its immunostimulant activity.
- ?kalamera, Dani,Antica, Mariastefania,Car, ?eljka,Dra?enovi?, Josip,Milkovi?, Lidija,Perokovi?, Vesna Petrovi?,Ribi?, Rosana,Stojkovi?, Ranko,Tomi?, Sr?anka
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supporting information
(2021/11/01)
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- Automated Quantification of Hydroxyl Reactivities: Prediction of Glycosylation Reactions
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The stereoselectivity and yield in glycosylation reactions are paramount but unpredictable. We have developed a database of acceptor nucleophilic constants (Aka) to quantify the nucleophilicity of hydroxyl groups in glycosylation influenced by the steric, electronic and structural effects, providing a connection between experiments and computer algorithms. The subtle reactivity differences among the hydroxyl groups on various carbohydrate molecules can be defined by Aka, which is easily accessible by a simple and convenient automation system to assure high reproducibility and accuracy. A diverse range of glycosylation donors and acceptors with well-defined reactivity and promoters were organized and processed by the designed software program “GlycoComputer” for prediction of glycosylation reactions without involving sophisticated computational processing. The importance of Aka was further verified by random forest algorithm, and the applicability was tested by the synthesis of a Lewis A skeleton to show that the stereoselectivity and yield can be accurately estimated.
- Chang, Chun-Wei,Lin, Mei-Huei,Chan, Chieh-Kai,Su, Kuan-Yu,Wu, Chia-Hui,Lo, Wei-Chih,Lam, Sarah,Cheng, Yu-Ting,Liao, Pin-Hsuan,Wong, Chi-Huey,Wang, Cheng-Chung
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supporting information
p. 12413 - 12423
(2021/05/03)
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- Carbon glycoside glycosylated tetravalent platinum compound as well as synthesis method and application thereof
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The invention provides a carbon glycoside glycosylated tetravalent platinum compound, a synthesis method and application thereof. R1 and R2 are independently C1-C4 lower alkanes, R3 is glucose, galactose, mannose and ribose, different sugars are used as raw materials, and a series of carbon glycoside glycosylated tetravalent platinum compounds are synthesized through protection and deprotection reaction and metallization reaction of the sugars. The synthesis method is simple, the used raw materials are cheap and easy to obtain, the glycosylated tetravalent platinum compound has the capacity of targeting glucose transporter protein and has potential application value in the field of cancer treatment, introduction of a C-glucosidic bond enables the series of compounds to have the capacity of resisting hydrolysis of beta-glucosidase, and the compound is expected to be applied to the field of oral antitumor drugs.
- -
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- Method for continuously synthesizing benzyl-substituted glucolactone by adopting microchannel reaction device
-
The invention discloses a method for continuously synthesizing benzyl-substituted glucolactone by adopting a microchannel reaction device. The method comprises the following steps: taking methyl-alpha-D-mannopyranoside as an initial raw material, preparing the methyl-alpha-D-mannopyranoside into an old organic solvent solution, and reacting the old organic solvent solution with an organic solvent solution of benzyl chloride in a first microreactor to generate methyl glucose with hydroxyl protected by benzyl; reacting a homogeneous solution formed by mixing a reaction solution of benzyl-substituted gluconic acid and a small amount of hydrochloric acid solution in a second microreactor for demethylation to generate hydroxyl benzyl-substituted glucose; and finally, reacting the reaction solution with an aqueous solution of hydrogen peroxide and sodium hydroxide and an organic solvent solution of tetramethylpiperidine nitrogen oxide in a third microreactor to generate the high-purity hypoglycemic drug Dapagliflozin intermediate benzyl substituted glucolactone. The method disclosed by the invention is higher in heat and mass transfer efficiency and easier to industrially amplify, the initial materials are simple, cheap and easily available, the process is simple, the obtained intermediate is high in purity and high in yield, the production cost can be effectively reduced, and the method is suitable for industrial production.
- -
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Paragraph 0010; 0043-0044; 0047; 0049; 0052-0054; 0057-0059
(2021/06/21)
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- Glucosylpolyphenols as Inhibitors of Aβ-Induced Fyn Kinase Activation and Tau Phosphorylation: Synthesis, Membrane Permeability, and Exploratory Target Assessment within the Scope of Type 2 Diabetes and Alzheimer's Disease
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Despite the rapidly increasing number of patients suffering from type 2 diabetes, Alzheimer's disease, and diabetes-induced dementia, there are no disease-modifying therapies that are able to prevent or block disease progress. In this work, we investigate the potential of nature-inspired glucosylpolyphenols against relevant targets, including islet amyloid polypeptide, glucosidases, and cholinesterases. Moreover, with the premise of Fyn kinase as a paradigm-shifting target in Alzheimer's drug discovery, we explore glucosylpolyphenols as blockers of Aβ-induced Fyn kinase activation while looking into downstream effects leading to Tau hyperphosphorylation. Several compounds inhibit Aβ-induced Fyn kinase activation and decrease pTau levels at 10 μM concentration, particularly the per-O-methylated glucosylacetophloroglucinol and the 4-glucosylcatechol dibenzoate, the latter inhibiting also butyrylcholinesterase and β-glucosidase. Both compounds are nontoxic with ideal pharmacokinetic properties for further development. This work ultimately highlights the multitarget nature, fine structural tuning capacity, and valuable therapeutic significance of glucosylpolyphenols in the context of these metabolic and neurodegenerative disorders.
- De Matos, Ana M.,Blázquez-Sánchez, M. Teresa,Bento-Oliveira, Andreia,De Almeida, Rodrigo F. M.,Nunes, Rafael,Lopes, Pedro E. M.,MacHuqueiro, Miguel,Cristóv?o, Joana S.,Gomes, Cláudio M.,Souza, Cleide S.,El Idrissi, Imane G.,Colabufo, Nicola A.,Diniz, Ana,Marcelo, Filipa,Oliveira, M. Concei??o,López, óscar,Fernandez-Bola?os, José G.,D?twyler, Philipp,Ernst, Beat,Ning, Ke,Garwood, Claire,Chen, Beining,Rauter, Amélia P.
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p. 11663 - 11690
(2020/11/26)
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- C-MANNOSIDE COMPOUNDS USEFUL FOR THE TREATMENT OF URINARY TRACT INFECTIONS
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Disclosed herein are new C-mannoside compounds and compositions and their application as pharmaceuticals for the treatment of human disease. Methods of inhibition of FimH activity in a human subject are also provided for the treatment diseases such as urinary tract infection.
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Page/Page column 21; 22
(2020/02/06)
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- C-Mannosyl Lysine for Solid Phase Assembly of Mannosylated Peptide Conjugate Cancer Vaccines
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Dendritic cells (DCs) are armed with a multitude of Pattern Recognition Receptors (PRRs) to recognize pathogens and initiate pathogen-tailored T cell responses. In these responses, the maturation of DCs is key, as well as the production of cytokines that help to accomplish T cell responses. DC-SIGN is a frequently exploited PRR that can effectively be targeted with mannosylated antigens to enhance the induction of antigen-specific T cells. The natural O-mannosidic linkage is susceptible to enzymatic degradation, and its chemical sensitivity complicates the synthesis of mannosylated antigens. For this reason, (oligo)mannosides are generally introduced in a late stage of the antigen synthesis, requiring orthogonal conjugation handles for their attachment. To increase the stability of the mannosides and streamline the synthesis of mannosylated peptide antigens, we here describe the development of an acid-stable C-mannosyl lysine, which allows for the inline introduction of mannosides during solid-phase peptide synthesis (SPPS). The developed amino acid has been successfully used for the assembly of both small ligands and peptide antigen conjugates comprising an epitope of the gp100 melanoma-associated antigen and a TLR7 agonist for DC activation. The ligands showed similar internalization capacities and binding affinities as the O-mannosyl analogs. Moreover, the antigen conjugates were capable of inducing maturation, stimulating the secretion of pro-inflammatory cytokines, and providing enhanced gp100 presentation to CD8+ and CD4+ T cells, similar to their O-mannosyl counterparts. Our results demonstrate that the C-mannose lysine is a valuable building block for the generation of anticancer peptide-conjugate vaccine modalities.
- Bruijns, Sven C. M.,Codée, Jeroen D. C.,Filippov, Dmitri V.,Hogervorst, Tim P.,Li, R. J. Eveline,Marino, Laura,Meeuwenoord, Nico J.,Overkleeft, Herman S.,Van Der Marel, Gijsbert A.,Van Kooyk, Yvette,Van Vliet, Sandra J.
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- Direct dehydrative glycosylation catalyzed by diphenylammonium triflate
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Methods for direct dehydrative glycosylations of carbohydrate hemiacetals catalyzed by diphenylammonium triflate under microwave irradiation are described. Both armed and disarmed glycosyl-C1-hemiacetal donors were efficiently glycosylated in moderate to excellent yields without the need for any drying agents and stoichiometric additives. This method has been successfully applied to a solid-phase glycosylation.
- Hsu, Mei-Yuan,Lam, Sarah,Lin, Mei-Huei,Lin, Su-Ching,Wang, Cheng-Chung,Wu, Chia-Hui
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supporting information
(2020/03/13)
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- Mapping mechanisms in glycosylation reactions with donor reactivity: Avoiding generation of side products
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The glycosylation reaction, which is key for the studies on glycoscience, is challenging due to its complexity and intrinsic side reactions. Thioglycoside is one of the most widely used glycosyl donors in the synthesis of complex oligosaccharides. However, one of the challenges is its side reactions, which lower its yield and limits its efficiency, thereby requiring considerable effort in the optimization process. Herein, we reported a multifaceted experimental approach that reveals the behaviors of side reactions, such as the intermolecular thioaglycon transformation and N-glycosyl succinimides, via the glycosyl intermediate. Our mechanistic proposal was supported by low temperature NMR studies that can further be mapped by utilizing relative reactivity values. Accordingly, we also presented our findings to suppress the generation of side products in solving this particular problem for achieving high-yield glycosylation reactions.
- Wang, Cheng-Chung,Chang, Chun-Wei,Lin, Mei-Huei,Wu, Chia-Hui,Chiang, Tsun-Yi
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p. 15945 - 15963
(2021/01/18)
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- New class of alkynyl glycoside analogues as tyrosinase inhibitors
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A new series of alkynyl glycoside analogues were designed and synthesized from cheap and a commercially available sugar by introduction of various alkynyl and alkyl groups at C-1 and C-6 positions of the sugar ring. The inhibitory abilities of alkynyl gly
- Saehlim, Natthiya,Athipornchai, Anan,Sirion, Uthaiwan,Saeeng, Rungnapha
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- Sodium sugar-translocator 2 inhibitor, its preparation and its pharmaceutical composition and use thereof
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The invention discloses an inhibitor for sodium-glucose co-transporter 2 (SGLT2), a preparation method and a pharmaceutical composition thereof, and application of the inhibitor and the pharmaceutical composition. Specifically, the invention discloses the SGLT2 inhibitor with a general formula (I) as described in the specification and pharmaceutically acceptable salts thereof, preparation process of the SGLT2 inhibitor, the pharmaceutical composition containing the inhibitor with the general formula (I) as described in the specification, and application of the inhibitor and the pharmaceutical composition in antidiabetic aspects.
- -
-
Paragraph 0201-0203
(2019/07/16)
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- Aza-carboside chalcone and preparation method thereof (by machine translation)
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The aza-carboside chalcone comprises a compound, wherein the compound of the general formula I or the general formula II is compatible with industrial production, has small toxic and side effects, has a rapid hypoglycemic effect, and can better relieve symptoms; namely, a diabetic patient . the invention provides a preparation method of the azinosine chalcone, which comprises a compound of general formula I or general formula II and an inorganic acid or an organic acid. (by machine translation)
- -
-
Paragraph 0089; 0091-0093
(2019/07/31)
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- Visible Light Enables Aerobic Iodine Catalyzed Glycosylation
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A versatile protocol for light induced catalytic activation of thioglycosides using iodine as an inexpensive and readily available photocatalyst was developed. Oxygen serves as a green and cost-efficient terminal oxidant and irradiation is performed with a common household LED-bulb. The scope of this glycosylation protocol was investigated in the synthesis of O-glycosides with yields up to 95 %.
- Krumb, Matthias,Lucas, Tobias,Opatz, Till
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supporting information
p. 4517 - 4521
(2019/08/06)
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- Establishment of Guidelines for the Control of Glycosylation Reactions and Intermediates by Quantitative Assessment of Reactivity
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Stereocontrolled chemical glycosylation remains a major challenge despite vast efforts reported over many decades and so far still mainly relies on trial and error. Now it is shown that the relative reactivity value (RRV) of thioglycosides is an indicator for revealing stereoselectivities according to four types of acceptors. Mechanistic studies show that the reaction is dominated by two distinct intermediates: glycosyl triflates and glycosyl halides from N-halosuccinimide (NXS)/TfOH. The formation of glycosyl halide is highly correlated with the production of α-glycoside. These findings enable glycosylation reactions to be foreseen by using RRVs as an α/β-selectivity indicator and guidelines and rules to be developed for stereocontrolled glycosylation.
- Chang, Chun-Wei,Wu, Chia-Hui,Lin, Mei-Huei,Liao, Pin-Hsuan,Chang, Chun-Chi,Chuang, Hsiao-Han,Lin, Su-Ching,Lam, Sarah,Verma, Ved Prakash,Hsu, Chao-Ping,Wang, Cheng-Chung
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supporting information
p. 16775 - 16779
(2019/11/03)
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- A monosaccharide dissolution of benzylating method
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The invention discloses a benzylation method for monosaccharide glucoside. The method includes the steps of sequentially adding monosaccharide glucoside, sodium hydride, methylbenzene and benzyl chloride to a reactor, raising the temperature to the reaction temperature of 60-130 DEG C, preserving heat till the reaction is completed, and conducting postprocessing on reaction liquid after the reaction ends to prepare a benzylation product of monosaccharide glucoside, wherein the benzylation product of monosaccharide glucoside is a product generated by conducting benzylation on all hydroxide radicals -OH on monosaccharide glucoside to generate -O-Bn, and Bn represents benzyl groups. Reaction solvent and extraction solvent are both methylbenzene, the postprocessing operation is simplified, the byproduct methylbenzene in the reaction process is consistent with the reaction solvent, recycled methylbenzene can be directly used as reaction solvent for the next batch without water removal, and the aims of simplifying operation, reducing sodium hydride and benzyl chloride unit consumption, effectively reducing generation of byproduct dibenzyl ether and reducing pollution are achieved.
- -
-
Paragraph 0039-0044; 0049
(2018/05/24)
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- REAGENTS AND METHODS FOR GLYCOSYLATION
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The invention provides methods and regents for the glycosylation of organic molecules. In one aspect, the invention provides a method for glycosylating a hydroxyl-containing organic compound (i.e., a glycosyl acceptor) comprising contacting a glycosyl don
- -
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Paragraph 00173
(2018/03/09)
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- An Empirical Understanding of the Glycosylation Reaction
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Reliable glycosylation reactions that allow for the stereo- and regioselective installation of glycosidic linkages are paramount to the chemical synthesis of glycan chains. The stereoselectivity of glycosylations is exceedingly difficult to control due to the reaction's high degree of sensitivity and its shifting, simultaneous mechanistic pathways that are controlled by variables of unknown degree of influence, dominance, or interdependency. An automated platform was devised to quickly, reproducibly, and systematically screen glycosylations and thereby address this fundamental problem. Thirteen variables were investigated in as isolated a manner as possible, to identify and quantify inherent preferences of electrophilic glycosylating agents (glycosyl donors) and nucleophiles (glycosyl acceptors). Ways to enhance, suppress, or even override these preferences using judicious environmental conditions were discovered. Glycosylations involving two specific partners can be tuned to produce either 11:1 selectivity of one stereoisomer or 9:1 of the other by merely changing the reaction conditions.
- Chatterjee, Sourav,Moon, Sooyeon,Hentschel, Felix,Gilmore, Kerry,Seeberger, Peter H.
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supporting information
p. 11942 - 11953
(2018/09/27)
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- Method for synthesizing 2,3,4,6-tetrabenzyl-D-glucopyranose
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The invention discloses a method for synthesizing 2,3,4,6-tetrabenzyl-D-glucopyranose. The method is characterized by comprising the following steps: a, dissolving alpha-D-methylglucoside into an organic solvent, introducing nitrogen, adding metal hydride
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-
Paragraph 0035; 0036; 0038; 0039; 0044; 0045; 0047; 0048
(2018/04/26)
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- Formation of and Glycosylation with Per-O-Acetyl Septanosyl Halides: Rationalizing Complex Reactivity En Route to p-Nitrophenyl Septanosides
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Protein–carbohydrate interactions are at the heart of many biological processes. For lectins, those interactions result simply in the association of two species, whereas for enzymes like glycosidases, association ultimately leads to cleavage and formation
- Pote, Aditya R.,Vannam, Raghu,Richard, Alissa,Gascón, José,Peczuh, Mark W.
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supporting information
p. 1709 - 1719
(2018/04/24)
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- Benzylation method for methyl glucosamine
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The invention provides a benzylation method for a methyl glucosamine. The method comprises the following steps: a methyl glucosamine, an alkali and an organic solvent are added to a reaction vessel which is provided with a reflux and water separator, a re
- -
-
Paragraph 0032; 0040; 0042; 0044; 0046
(2018/03/13)
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- Sugar hydrazide imides: A new family of glycosidase inhibitors
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The preparation of a novel type of iminosugar including a hydrazide imide moiety is described. The sugar hydrazide imides (3S,4S,5R,6R)-1-amino-3,4,5-trihydroxy-6-(hydroxymethyl)-2-iminopiperidine acetate and (3S,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethy
- Lindb?ck, Emil,Lopéz, óscar,Tobiesen, ?dne,Fernández-Bola?os, José G.,Sydnes, Magne O.
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supporting information
p. 8709 - 8712
(2017/11/03)
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- C-GLYCOSIDE COMPOUNDS USEFUL FOR TREATING DISEASE
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The present invention relates to mannoside derivative compounds useful as inhibitors of FimH and methods for the treatment or prevention of urinary tract infection.
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-
Paragraph 00197
(2017/10/06)
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- Macrocyclic bis-thioureas catalyze stereospecific glycosylation reactions
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Carbohydrates are involved in nearly all aspects of biochemistry, but their complex chemical structures present long-standing practical challenges to their synthesis. In particular, stereochemical outcomes in glycosylation reactions are highly dependent on the steric and electronic properties of coupling partners; thus, carbohydrate synthesis is not easily predictable. Here we report the discovery of a macrocyclic bis-thiourea derivative that catalyzes stereospecific invertive substitution pathways of glycosyl chlorides. The utility of the catalyst is demonstrated in the synthesis of trans-1,2-, cis-1,2-, and 2-deoxy-β-glycosides. Mechanistic studies are consistent with a cooperative mechanism in which an electrophile and a nucleophile are simultaneously activated to effect a stereospecific substitution reaction.
- Park, Yongho,Harper, Kaid C.,Kuhl, Nadine,Kwan, Eugene E.,Liu, Richard Y.,Jacobsen, Eric N.
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p. 162 - 166
(2017/01/24)
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- Total synthesis of N-butyl-1-deoxynojirimycin
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N-Butyl-1-deoxynojirimycin (NB-DNJ) derived from imino sugar deoxynojirimycin (DNJ) has been approved for the treatment of Gaucher’s disease. Herein, a facile and efficient synthetic procedure for NB-DNJ has been described. Comparing to the methods reported previously,methanesulfonyl group was used as a leaving group for easy displacement upon attack by the imine in the sugar ring, leading to a high yield during the introduction of the n-butyl group. Thismethod can serve as an excellent protocol for the synthesis of DNJ derivatives with a variety of N-alkyl substituents and for large-scale production.
- Wang, Jiajia,Zhao, Yunyan,Zhao, Wei,Wang, Peng,Li, Jing
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p. 445 - 454
(2017/08/23)
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- Four Different Regioisomeric Polycarbonates Derived from One Natural Product, d -Glucose
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Strategies for the preparation of polycarbonates, derived from the natural product d-glucose, which have the potential to degrade back into their bioresorbable starting material and CO2, were developed. By employing established carbohydrate pro
- Lonnecker, Alexander T.,Lim, Young H.,Felder, Simcha E.,Besset, Céline J.,Wooley, Karen L.
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p. 7857 - 7867
(2016/11/09)
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- Selenoureido-iminosugars: A new family of multitarget drugs
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Herein we report the synthesis of N-alkylated deoxynojirimycin derivatives decorated with a selenoureido motif at the hydrocarbon tether as an example of unprecedented multitarget agents. Title compounds were designed as dual drugs for tackling simultaneously the Gaucher disease (by selective inhibition of β-glucosidase, Ki= 1.6–5.5 μM, with improved potency and selectivity compared to deoxynojirimycin) and its neurological complications (by inhibiting AChE, Kiup to 5.8 μM). Moreover, an excellent mimicry of the selenoenzyme glutathione peroxidase was also found for the catalytic scavenging of H2O2(Kcat/Kuncatup to 640) using PhSH as a cofactor, with improved activity compared to known positive controls, like (PhSe)2and ebselen; therefore, such compounds are also excellent scavengers of peroxides, an example of reactive oxygen species present at high concentrations in patients of Gaucher disease and neurological disorders.
- Olsen, Jacob Ingemar,Plata, Gabriela B.,Padrón, José M.,López, óscar,Bols, Mikael,Fernández-Bola?os, José G.
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p. 155 - 160
(2016/08/01)
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- Total Synthesis of (+)-Vicenin-2
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The bis-C-glucosyl flavonoid vicenin-2 (1) has been synthesized by exploiting bis-C-glycosylation of 1,3,5-trifluorobenzene and aromatic nucleophilic substitution to transform fluorine atoms to oxygen functions in excellent yield.
- Ho, Thanh C.,Kamimura, Haruki,Ohmori, Ken,Suzuki, Keisuke
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supporting information
p. 4488 - 4490
(2016/09/28)
-
- GLUCOSE-RESPONSIVE INSULIN CONJUGATES
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Insulin conjugates comprising an insulin analog molecule covalently attached to at least one bi-dentate linker having two arms, each arm independently attached to a ligand comprising a saccharide and wherein the saccharide for at least one ligand of the linker is fucose are disclosed. The insulin conjugates display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.
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Page/Page column 143
(2016/10/31)
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- Conversion of β-glycopyranoside to α-glycopyranoside by photo-activated radical reaction
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By using carbon tetrachloride as the chloride radical and boron trifluoride etherate as the Lewis acid, the halogen-light-activated anomeric inversion of glycoside was achieved. This reaction is a novel guide to invert the glycosidic bond from a β-anomer to an α-anomer.
- Lai, Yu-Chen,Luo, Chin-Hung,Chou, Hsin-Chun,Yang, Cheng-Jhang,Lu, Le,Chen, Chien-Sheng
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supporting information
p. 2474 - 2477
(2016/05/24)
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- A versatile glycosylation strategy: Via Au(III) catalyzed activation of thioglycoside donors
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Among various methods of chemical glycosylations, glycosylation by activation of thioglycoside donors using a thiophilic promoter is an important strategy. Many promoters have been developed for the activation of thioglycosides. However, incompatibility w
- Vibhute, Amol M.,Dhaka, Arun,Athiyarath, Vignesh,Sureshan, Kana M.
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p. 4259 - 4263
(2016/07/06)
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- Synthesis of Unprecedented Sulfonylated Phosphono-exo-Glycals Designed as Inhibitors of the Three Mycobacterial Galactofuranose Processing Enzymes
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This study reports a new methodology to synthesize exo-glycals bearing both a sulfone and a phosphonate. This synthetic strategy provides a way to generate exo-glycals displaying two electron-withdrawing groups and was applied to eight different carbohydrates from the furanose and pyranose series. The Z/E configurations of these tetrasubstituted enol ethers could be ascertained using NMR spectroscopic techniques. Deprotection of an exo-glycal followed by an UMP (uridine monophosphate) coupling generated two new UDP (uridine diphosphate)-galactofuranose analogues. These two Z/E isomers were evaluated as inhibitors of UGM, GlfT1, and GlfT2, the three mycobacterial galactofuranose processing enzymes. Molecule 46-(E) is the first characterized inhibitor of GlfT1 reported to date and was also found to efficiently inhibit UGM in a reversible manner. Interestingly, GlfT2 showed a better affinity for the (Z) isomer. The three enzymes studied in the present work are not only interesting because, mechanistically, they are still the topic of intense investigations, but also because they constitute very important targets for the development of novel antimycobacterial agents.
- Frédéric, Christophe J.-M.,Tikad, Abdellatif,Fu, Jian,Pan, Weidong,Zheng, Ruixiang B.,Koizumi, Akihiko,Xue, Xiaochao,Lowary, Todd L.,Vincent, Stéphane P.
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supporting information
p. 15913 - 15920
(2016/10/25)
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- Iodine monochloride (ICl) as a highly efficient, green oxidant for the oxidation of alcohols to corresponding carbonyl compounds
-
Iodine monochloride (ICl) was discovered to be a highly efficient, green oxidant, which can oxidize aldose hemiacetals, diarylmethanols, arylalkylmethanols, anddialkylmethanols to the corresponding aldose lactones, diarylmethanones, arylalkylmethanones, and dialkylmethanones, respectively, in high yields. ICl as a green, metal-free oxidant is characterized by mild reaction condition, short reaction time, good yield, and broad scope.
- Wei, Peng,Zhang, Datong,Gao, Zhigang,Cai, Wenqing,Xu, Weiren,Tang, Lida,Zhao, Guilong
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supporting information
p. 1457 - 1470
(2015/05/20)
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- Carbohydrate based hyper-crosslinked organic polymers with -OH functional groups for CO2 separation
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Recently, microporous organic polymers, especially those hyper-crosslinked from functionalized aromatic monomers, have been shown to be effective for CO2 capture and storage with considerable capacity and selectivity. Herein, a class of novel m
- Li, Haiying,Meng, Bo,Mahurin, Shannon M.,Chai, Song-Hai,Nelson, Kimberly M.,Baker, David C.,Liu, Honglai,Dai, Sheng
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supporting information
p. 20913 - 20918
(2015/11/03)
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- GLUCOSE-RESPONSIVE INSULIN CONJUGATES
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Insulin conjugates comprising an insulin molecule covalently attached to at least one bi-dentate linker having two arms, each arm independently attached to a ligand comprising a saccharide and wherein the saccharide for at least one ligand of the linker is fucose are disclosed. The insulin conjugates display a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.
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Paragraph 0515
(2015/04/21)
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- Method for preventing cancer metastasis
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The present invention relates to the use of a specific family of glycerolipid compounds of formula (I) described in the detailed description or the manufacture of a medicament for the prevention or for the treatment of cancer metastasis.
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Page/Page column 20
(2015/11/10)
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- Gold-catalysed glycosylation reaction using an easily accessible leaving group
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Gold(iii)-catalysed glycosylation reaction has been developed by employing a new and easily accessible leaving group synthesized from ethyl cyanoacetate. Several nucleophiles like alcohols, thiols, allyltrimethylsilane, trimethylsilyl azide and triethylsilane have been reacted to make the corresponding glycosides in good yields and with marginal to excellent α-selectivity. This journal is
- Koppolu, Srinivasa Rao,Niddana, Ramana,Balamurugan, Rengarajan
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supporting information
p. 5094 - 5097
(2015/05/13)
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- Application of 2-substituted benzyl groups in stereoselective glycosylation
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The use of 2-O-(2-nitrobenzyl) and 2-O-(2-cyanobenzyl) groups controls stereoselective formation of 1,2-trans-glycosidic linkages via the arming participation effect. The observed stereoselectivity likely arises from the intramolecular formation of cyclic intermediate between the electron-rich substituent and the donor oxacarbenium ion providing the expected facial selectivity for attack of the glycoside acceptor. The stereodirecting effect of the 2-nitro- and 2-cyanobenzyl groups attached at the remote position (C-3, C-4, and C-6) of the donor molecule have also been investigated. To prove the postulated mechanism based on the participation effect of 2-substituted benzyl groups in the glycosylation stereoselectivity we used DFT theoretical calculation methodology.
- Buda, Szymon,Nawj, Miroslaw,Golbiowska, Patrycja,Dyduch, Karol,Michalak, Artur,Mlynarski, Jacek
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p. 770 - 780
(2015/03/03)
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- NEW C-GLYCOSYLPOLYPHENOL ANTIDIABETIC AGENTS, EFFECT ON GLUCOSE TOLERANCE AND INTERACTION WITH BETA-AMYLOID. THERAPEUTIC APPLICATIONS OF THE SYNTHESIZED AGENT(S) AND OF GENISTA TENERA ETHYL ACETATE EXTRACTS CONTAINING SOME OF THOSE AGENTS
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The present invention concerns the antidiabetic-activity of compounds type A, namely of 8-β-D-glucosylgenistein, which is not toxic to eukaryotic cells and has demonstrated to produce complete normalization of fasting hyperglycaemia, to reduce excessive p
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Paragraph 0077; 0084
(2015/02/19)
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- Carbohydrate-derived iminium salt organocatalysts for the asymmetric epoxidation of alkenes
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A new family of carbohydrate-based dihydroisoquinolinium salts has been prepared and tested for potential as asymmetric catalysts for the epoxidation of unfunctionalized alkene substrates, providing up to 57% ee in the product epoxides.
- Bulman Page, Philip C.,Chan, Yohan,Liddle, John,Elsegood, Mark R.J.
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p. 7283 - 7305
(2017/09/13)
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- Tin-mediated regioselective benzylation and allylation of polyols: Applicability of a catalytic approach under solvent-free conditions
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The first catalytic version of the stannylene-mediated benzylation and allylation of polyols is reported. The methodology is based on a simple solvent-free protocol that significantly advances, in terms of both experimental ease and synthetic scope, the a
- Giordano, Maddalena,Iadonisi, Alfonso
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p. 213 - 222
(2014/01/17)
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- CARBOHYDRATE PHOSPHONATE DERIVATIVES AS MODULATORS OF GLYCOSYLATION
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Compounds of Formula (I) are useful as modulators of glycosylation. Compounds of Formula (I) have the following structure: (I) and the definitions of the other variables are provided herein.
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Paragraph 0120
(2014/09/03)
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- A biophysical study with carbohydrate derivatives explains the molecular basis of monosaccharide selectivity of the Pseudomonas aeruginosa lectin lecB
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The rise of resistances against antibiotics in bacteria is a major threat for public health and demands the development of novel antibacterial therapies. Infections with Pseudomonas aeruginosa are a severe problem for hospitalized patients and for patients suffering from cystic fibrosis. These bacteria can form biofilms and thereby increase their resistance towards antibiotics. The bacterial lectin LecB was shown to be necessary for biofilm formation and the inhibition with its carbohydrate ligands resulted in reduced amounts of biofilm. The natural ligands for LecB are glycosides of D-mannose and L-fucose, the latter displaying an unusual strong affinity. Interestingly, although mannosides are much weaker ligands for LecB, they do form an additional hydrogen bond with the protein in the crystal structure. To analyze the individual contributions of the methyl group in fucosides and the hydroxymethyl group in mannosides to the binding, we designed and synthesized derivatives of these saccharides.We report glycomimetic inhibitors that dissect the individual interactions of their saccharide precursors with LecB and give insight into the biophysics of binding by LecB. Furthermore, theoretical calculations supported by experimental thermodynamic data suggest a perturbed hydrogen bonding network for mannose derivatives as molecular basis for the selectivity of LecB for fucosides. Knowledge gained on the mode of interaction of LecB with its ligands at ambient conditions will be useful for future drug design.
- Sommer, Roman,Exner, Thomas E.,Titz, Alexer
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- Exploiting the therapeutic potential of 8-β- d -glucopyranosylgenistein: Synthesis, antidiabetic activity, and molecular interaction with islet amyloid polypeptide and amyloid β-peptide (1-42)
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8-β-d-Glucopyranosylgenistein (1), the major component of Genista tenera, was synthesized and showed an extensive therapeutical impact in the treatment of STZ-induced diabetic rats, producing normalization of fasting hyperglycemia and amelioration of exce
- Jesus, Ana R.,Dias, Catarina,Matos, Ana M.,De Almeida, Rodrigo F.M.,Viana, Ana S.,Marcelo, Filipa,Ribeiro, Rogério T.,Macedo, Maria P.,Airoldi, Cristina,Nicotra, Francesco,Martins, Alice,Cabrita, Eurico J.,Jiménez-Barbero, Jesús,Rauter, Amélia P.
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p. 9463 - 9472
(2015/02/02)
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- GEM-DIFLUORINATED C-GLYCOSIDE COMPOUNDS AS ANTI-CANCER AGENTS
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The present document describes a synthesis of a class of gem-difluorinated C-glycoside compounds derived from podophyllotoxin, which may be used, but not exclusively, in oncology for the treatment of cancer. More particularly, the podophyllotoxin gem-difluorinated C-glycoconjugated derivatives display improved conformational and chemical stability, and improved cytotoxicity exhibited against drug-resistant cancer cell lines.
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Paragraph 00125; 00126; 00127
(2014/07/23)
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- Neighbouring group participation during glycosylation: Do 2-substituted ethyl ethers participate?
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The development of new protecting groups that undergo neighbouring group participation (NGP) via six-membered ring intermediates to promote the formation of α-1,2-cis glycosidic linkages complements the established use of 5-ring NGP in terms of stereochem
- Cox, Daniel J.,Singh, Govind P.,Watson, Andrew J. A.,Fairbanks, Antony J.
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p. 4624 - 4642
(2014/08/05)
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- Macrocyclic glycohybrid toolbox identifies novel antiangiogenesis agents from zebrafish assay
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A practical and modular approach to obtain a diverse set of 14-membered macrocyclic compounds from carbohydrates is developed that utilizes functional groups at C-1 and C-5. The evaluation of this toolbox in various zebrafish assays led to the identificat
- Dasari, Bhanudas,Jogula, Srinivas,Borhade, Ramdas,Balasubramanian, Sridhar,Chandrasekar, Gayathri,Kitambi, Satish Srinivas,Arya, Prabhat
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supporting information
p. 432 - 435
(2013/04/23)
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