- PROCESS OF SYNTHESIS OF β-6'SULFOQUINOVOSYL DIACYLGLYCEROLS
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The present invention relates to a synthesis process of β-6-sulfoquinovosyl-diacylglycerols. In particular, said process is for the synthesis of the compounds 1,2-O-distearoyl-3-O-(β- sulfoquinovosyl)-R/S-glycerol, 1,2-O-distearoyl-3-O-(β-sulfoquinovosyl)-R-glycerol or 1,2- O-distearoyl-3-O-(β-sulfoquinovosyl)-S-glycerol, named respectively Sulfavant A, Sulfavant R and Sulfavant S.
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- Synthesis of malformin-A1, C, a glycan, and an aglycon analog: Potential scaffolds for targeted cancer therapy
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Improvement in therapeutic efficacy while reducing chemotherapeutic side effects remains a vital objective in synthetic design for cancer treatment. In keeping with the ethos of therapeutic development and inspired by the Warburg effect for augmenting biological activities of the malformin family of cyclic-peptide natural products, specifically anti-tumor activity, a β-glucoside of malformin C has been designed and synthesized utilizing precise glycosylation and solution phase peptide synthesis. We optimized several glycosylation procedures utilizing different donors and acceptors. The overarching goal of this study was to ensure a targeted delivery of a glyco-malformin C analog through the coupling of D-glucose moiety; selective transport via glucose transporters (GLUTs) into tumor cells, followed by hydrolysis in the tumor microenvironment releasing the active malformin C a glycon analog. Furthermore, total synthesis of malformin C was carried out with overall improved strategies avoiding unwanted side reactions thus increasing easier purification. We also report on an improved solid phase peptide synthesis protocol for malformin A1.
- Andreana, Peter R.,Hossain, Farzana,Nishat, Sharmeen
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- Revealing Functional Significance of Interleukin-2 Glycoproteoforms Enabled by Expressed Serine Ligation
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Naturally occurring interleukin-2 (IL-2) is a pleiotropic glycoprotein that regulates immune responses by controlling the differentiation and homeostasis of T cells. Non-glycosylated IL-2 has been used in clinical settings for three decades. However, the function of the O-glycan of native IL-2 remains elusive. Herein, to stress this issue, we report a highly efficient semi-synthesis of homogeneous glycosylated IL-2 with various glycoproteoforms on a multi-milligram scale. The glycopeptide fragment was prepared by chemical synthesis and then merged with recombinant fragment via a serine ligation to generate the desired glycoprotein in a single operation. Biological evaluation of the homogenous glycoprotein library reveals that the activity of IL-2 in activating individual T cell subset is glycan dependent, thus highlighting the possibility of further improving current clinical medicine.
- Cao, Qi,Li, Bin,Liu, Jiazhi,Liu, Lizhen,Liu, Xinnan,Shao, Hong,Tao, Houchao,Wang, Can,Wang, Ping,Xue, Dongxiang,Ye, Farong,Yu, Biao,Zhao, Hongbo,Zhao, Jie
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supporting information
(2022/01/31)
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- Total synthesis of three natural phenethyl glycosides
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Phenethyl glycosides having phenolic or methoxy functions at benzene rings are substances widely occurring in nature. This kind of compounds has been shown to have anti-oxidant, anti-inflammatory, and anticancer activities. However, some of them are not naturally abundant, thus the synthesis of such molecules is desirable. In this paper, natural phenethyl glycosides 3 and 4 were first totally synthesized from easily available materials with overall yields of 50.5% and 40.1%, respectively. And a new synthetic route to obtain natural phenethyl glycoside 2 in 46.2% yield was also described.
- Dong, Hong-Bo,Meng, Jian,Yao, Zhong-Quan,Luo, Hong-Bing,Zhang, Jing-Xia,Du, Wei-Hong,Tang, Ke-Hui,Cao, Sheng-Hua
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p. 284 - 293
(2020/03/03)
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- First total syntheses of two natural glycosides
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Isosyringinoside (1) and 3-(O-β-D-glucopyranosyl)-α-(O-β-D-glucopyranosyl)-4-hydroxy phenylethanol (2), the natural bioactive compounds contained unique structures, were first totally synthesized using easily available materials in short convenient routes with overall yields of 20.2% and 27.0%, respectively. An efficient total synthesis of 1 was developed in six steps, which contained two key steps of highly regioselective glycosylation without any selective protection steps. The seven-step synthesis of 2 involved two steps of regioselective glycosylations using BF3–O(C2H5)2 and TMSOTf as catalysts, respectively.
- Dong, Hongbo,Du, Weihong,Yao, Zhongquan,Wu, Min,Luo, Hongbing,He, Yujiao,Cao, Shenghua
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- Glucose-containing nitrogen-containing aromatic ring derivative and application thereof
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The invention belongs to the technical field of medicines, and relates to a glucose-containing nitrogen-containing aromatic ring derivative and application thereof, and a pharmaceutical composition containing the compound. The invention also relates to a
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Paragraph 0159-0164
(2021/06/06)
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- Self-Promoted Glycosylation for the Synthesis of β-N-Glycosyl Sulfonyl Amides
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N-Glycosyl N-sulfonyl amides have been synthesized by a self-promoted glycosylation, i. e. without any catalysts, promotors or additives. When the reactions were carried out at lower temperatures a mixture of N- and O-glycosides were observed, where the latter rearranged to give the β-N-glycosides at elevated temperatures. By this method sulfonylated asparagine derivatives can be selectively β-glycosylated in high yields by trichloroacetimidate glycosyl donors of different reactivity including protected glucosamine derivatives. The chemoselectivity in the glycosylations as well as the rearrangements from O-glycosides to β-N-glycosides gives information of the glycosylation mechanism. This method gives access to glycosyl sulfonyl amides under mild conditions.
- Ma?a, Patrycja,Pedersen, Christian Marcus
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supporting information
p. 5685 - 5689
(2021/08/30)
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- 3'-KETOGLYCOSIDE COMPOUND FOR THE SLOW RELEASE OF A VOLATILE ALCOHOL
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The present invention relates to a 3'-ketoglycoside compound defined by formula (I) and its use for controlled release of alcohols, in particular alcohols showing an insect repellent effect. It relates also to a process for preparing the 3'-ketoglycoside compound of formula (I). It further relates to a composition comprising a 3'- ketoglycoside compound of formula (I). It relates also to the use of a 3'-ketoglycoside compound of formula (I) for the controlled release of alcohols. It related also to a method of use of such composition.
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- An alternative approach for the synthesis of sulfoquinovosyldiacylglycerol
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Sulfoquinovosyldiacylglycerol (SQDG) is a glycolipid ubiquitously found in photosyn-thetically active organisms. It has attracted much attention in recent years due to its biological ac-tivities. Similarly, the increasing demand for vegan and functional foods has led to a growing interest in micronutrients such as sulfolipids and their physiological influence on human health. To study this influence, reference materials are needed for developing new analytical methods and providing enough material for model studies on the biological activity. However, the availability of these materials is limited by the difficulty to isolate and purify sulfolipids from natural sources and the unavailability of chemical standards on the market. Consequently, an alternative synthetic route for the comprehensive preparation of sulfolipids was established. Here, the synthesis of a sulfolipid with two identical saturated fatty acids is described exemplarily. The method opens possibilities for the preparation of a diverse range of interesting derivatives with different saturated and unsatu-rated fatty acids.
- Domey, Hendrik,Fischer, Judith,Rohn, Sascha,Sitz, Tobias
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- GLUTs-targeted glycosylated tetravalent platinum compound, synthesis method and application thereof
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The invention provides a GLUTs-targeted glycosylated tetravalent platinum compound, a synthesis method and application thereof; the structural general formula of the GLUTs-targeted glycosylated tetravalent platinum compound is shown in the specification, wherein R1 is one of glucose, galactose, mannose and rhamnose; and R2 and R3 are independently C1-C4 lower alkanes. According to the invention, a glycosyl group is introduced into a tetravalent platinum parent nucleus; a series of novel glycosylation modified tetravalent platinum compounds are designed and synthesized; the targeting property of a medicine to tumour cells is improved by utilizing sugar transporter GLUTs highly expressed on the surfaces of the tumour cells; the anti-cancer and anti-tumour capacities are further improved; the in-vivo anti-tumour activity result shows that the series of compounds can inhibit tumour growth to a certain extent, and have relatively high safety is shown; and the potential of further research and development is achieved.
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Paragraph 0058-0060; 0062
(2021/10/27)
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- Chemical glucosylation of pyridoxine
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The chemical synthesis of pyridoxine-5′-β-D-glucoside (5′-β-PNG) was investigated using various glucoside donors and promoters. Hereby, the combination of α4,3-O-isopropylidene pyridoxine, glucose vested with different leaving and protecting groups and the application of stoichiometric amounts of different promoters was examined with regards to the preparation of the twofold protected PNG. Best results were obtained with 2,3,4,6-tetra-O-acetyl-D-glucopyranosyl fluoride and boron trifluoride etherate (2.0 eq.) as promoter at 0 °C (59%). The deprotection was accomplished stepwise with potassium/sodium hydroxide in acetonitrile/water followed by acid hydrolysis with formic acid resulting in the chemical synthesis of 5′-β-PNG.
- Bachmann, Thomas,Rychlik, Michael
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supporting information
(2020/02/13)
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- Oligosaccharide-camptothecin conjugates as potential antineoplastic drugs: Design, synthesis and biological evaluation
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Thirty novel 20 (S)–O-linked camptothecin (CPT) glycoconjugates were synthesized. They showed more potent in vitro cytotoxicities over irinotecan, but very weak direct topoisomerase I (Topo I) inhibition was observed at 100.0 μM. Oligosaccharide types, length of a PEG linker and acetyl groups exerted obvious effects on cytotoxicity, selectivity, water solubility and stability of the newly synthesized CPT glycoconjugates. Construct 40, with a bleomycin (BLM) disaccharide linked to diethylene glycol in the introduced ester moiety, demonstrated a superior antitumor activity and a distinct selectivity compared to CPT. No toxicity was detectable in animal acute toxicity intravenously (160 mg/kg). Collectively, attachment of oligosaccharides with tumor targeting to 20 (S)–OH of CPT could offer a solution to the daunting problems posed by current Topo I poisons.
- Li, Maolin,Ye, Wenchong,Fu, Kaishuo,zhou, Cui,Shi, Yonghui,Huang, Weiping,Chen, Wenming,Hu, Jiliang,Jiang, Zhilin,Zhou, Wen
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- Synthesis and cytotoxic property of annonaceous acetogenin glycoconjugates
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Background: Annonaceous acetogenins (ACGs) are secondary metabolites produced by the Annonaceae family and display potent anticancer activity against various cancer cell lines. Squamocin and bullatacin are two examples of ACGs that show promising antitumor activity; however, preclinical data are not sufficient partly due to their being highly lipophilic and poorly soluble in water. These compounds also display high toxicity to normal cells. Due to these disadvantageous properties, the therapeutic potential of squamocin and bullatacin as antitumor agents has not been fully evaluated. Methods: In order to enhance their water solubility and potentially improve their cancer targeting, squamocin and bullatacin were conjugated to a glucose or galactose to yield glycosylated derivatives by direct glycosylation or the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction (the click reaction). The synthesized compounds were evaluated for their anticancer property against HeLa, A549 and HepG2 cancer cell lines using MTT assay. Results: Nine glycosyl derivatives were synthesized and structurally characterized. Most of them show comparable in vitro cytotoxicity against HeLa, A549 and HepG2 cancer cell lines as their parent compounds squamocin and bullatacin. It appears that the type of sugar residue (glucose or galactose), the position at which the sugar residue is attached, and whether or not a linking spacer is present do not affect the potency of these derivatives much. The solubility of galactosylated squamocin 13 in phosphate buffer saline (PBS, pH = 7) is greatly improved (1.37 mg/mL) in comparison to squamocin (not detected in PBS). Conclusion: The conjugation of a glucose or galactose to squamocin and bullatacin yields glycosyl derivatives with similar level of anticancer activity in tested cell lines. Further studies are needed to demonstrate whether or not these compounds show reduced toxicity to normal cells and their therapeutic potential as antitumor agents.
- Shi, Jing-Fang,Wu, Ping,Cheng, Xiao-Li,Wei, Xiao-Yi,Jiang, Zi-Hua
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p. 4993 - 5004
(2020/11/23)
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- Tea leaf perfumery precursor glucoside and synthesizing method thereof
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The invention relates to a tea leaf perfumery precursor glucoside and a synthesizing method thereof. The synthesizing method comprises the following steps of synthesizing ten glucosides including aromatic alcohol ( alkanol )-beta -D-glucosides and aromatic alcohol (alkanol )-beta -D-primrose indicans. The synthesizing method disclosed by the invention is a glucoside synthesizing method which is good in selectivity, high in production rate and low in cost.
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- Preparation, supramolecular aggregation and immunological activity of the bona fide vaccine adjuvant sulfavant S
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In aqueous conditions, amphiphilic bioactive molecules are able to form self-assembled colloidal structures modifying their biological activity. This behavior is generally neglected in preclinical studies, despite its impact on pharmacological development. In this regard, a significative example is represented by a new class of amphiphilic marine-inspired vaccine adjuvants, collectively named Sulfavants, based on the β-sulfoquinovosyl-diacylglyceride skeleton. The family includes the lead product Sulfavant A (1) and two epimers, Sulfavant R (2) and Sulfavant S (3), differing only for the stereochemistry at C-2 of glycerol. The three compounds showed a significant difference in immunological potency, presumably correlated with change of the aggregates in water. Here, a new synthesis of diastereopure 3 was achieved, and the study of the immunomodulatory behavior of mixtures of 2/3 proved that the bizarre in vitro response to 1–3 effectively depends on the supramolecular aggregation states, likely affecting the bioavailability of agonists that can effectively interact with the cellular targets. The evidence obtained with the mixture of pure Sulfavant R (2) and Sulfavant S (3) proves, for the first time, that supramolecular organization of a mixture of active epimers in aqueous solution can bias evaluation of their biological and pharmacological potential.
- Manzo, Emiliano,Fioretto, Laura,Gallo, Carmela,Ziaco, Marcello,Nuzzo, Genoveffa,D’Ippolito, Giuliana,Borzacchiello, Assunta,Fabozzi, Antonio,de Palma, Raffaele,Fontana, Angelo
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- Short gram-scale synthesis of sulfavant A
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Recently, we reported the promising activity of a novel class of sulfoquinovosyl-diacylglycerols named Sulfavants as molecular vaccine adjuvants. Herein, we describe a modified and improved chemical synthesis of the lead product Sulfavant A (1), with the aim to produce from milligrams to 10 g of the pure compound that is necessary for the preclinical development. Starting from the versatile synthesis based on the trichloroacetimidate methodology, up-scaled preparation of Sulfavant A (1) was achieved in 11 steps by elimination and modification of those reactions that negatively affected the overall yield by the previous procedure. The novel strategy gave 17% overall yield of the target compound 1 and also paved the way for the gram-scale preparation of a wide range of other charged and neutral glycoglycerolipids.
- Ziaco, Marcello,Fioretto, Laura,Nuzzo, Genoveffa,Fontana, Angelo,Manzo, Emiliano
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p. 2728 - 2733
(2020/11/18)
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- Synthesis of 13C-labelled sulfated N-acetyl-d-lactosamines to aid in the diagnosis of mucopolysaccharidosis diseases
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Morquio A syndrome is an autosomal mucopolysaccharide storage disorder that leads to accumulation of keratan sulfate. Diagnosis of this disease can be aided by measuring the levels of keratan sulfate in the urine. This requires the liquid chromatography tandem mass spectrometry (LCMS/MS) measurement of sulfated N-acetyl-d-lactosamines in the urine after cleavage of the keratan sulfate with keratanase II. Quantification requires isotopically-labelled internal standards. The synthesis of these 13C6-labelled standards from 13C6-galactose and N-acetylglucosamine is described. The required protected disaccharide is prepared utilising a regioselective, high yielding β-galactosylation of a partially protected glucosamine acceptor and an inverse addition protocol. Subsequent synthesis of the 13C6-labelled mono and disulfated N-acetyllactosamines was achieved in five and eight steps, respectively, from this intermediate to provide internal standards for the LCMS/MS quantification of keratan sulfate in urine.
- Cameron, Scott A.,Zubkova, Olga V.,Toms, Steven,Furneaux, Richard H.,Rendle, Phillip M.
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- Substrate and preparation method and application thereof
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The invention discloses a substrate namely alpha-D-glucoside for detecting activity of alpha-glucosidases, and further discloses a synthesis technology of the substrate. The synthesis technology comprises the steps of enabling a compound alpha-D-glucose and acetyl chloride to be subjected to a reaction, and performing purification to obtain alpha-D- pentacetylglucose; catalyzing the obtained substances with N,N-Dimethyl-1,3-diaminopropane, performing pickling, performing extraction, performing drying, and performing purifying to obtain 2,3,4,6-tetra-O-acetyl-alpha-D-acetyl-glucosamine; catalyzing the obtained substances in a dichloromethane solution, performing a reaction with trichloroacetonitrile, performing filtering, and performing purifying to obtain 2,3,4,6-tetra-O-acetyl-beta-D-glucosyl trichloroacetimidate; performing catalyzing on the obtained substances in a dichloromethane solution, performing a reaction with chromogen or fluorophore, performing extraction, merging organic phases, performing drying, performing concentrating, performing methanol redissolution, performing crystal nourishing at 4 DEG C, and performing filtering to obtain 2,3,4,6-tetra-O-acetyl-alpha-D-glucoside; and catalyzing the obtained substances in a methanolic solution, performing a reaction, then performing decoloring adsorption, performing filtering, and performing purifying. The synthesis technology of the substrate is simple and high in yield, the sensitivity of a reagent kit can be improved, the stability is good, and the specificity is high.
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Paragraph 0022; 0024
(2019/05/15)
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- Chemo-enzymatic synthesis of p-nitrophenyl β-D-galactofuranosyl disaccharides from Aspergillus sp. fungal-type galactomannan
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β-D-Galactofuranose (Galf) is a component of polysaccharides and glycoconjugates. There are few reports about the involvement of galactofuranosyltransferases and galactofuranosidases (Galf-ases) in the synthesis and degradation of galactofuranose-containing glycans. The cell walls of filamentous fungi in the genus Aspergillus include galactofuranose-containing polysaccharides and glycoconjugates, such as O-glycans, N-glycans, and fungal-type galactomannan, which are important for cell wall integrity. In this study, we investigated the synthesis of p-nitrophenyl β-D-galactofuranoside and its disaccharides by chemo-enzymatic methods including use of galactosidase. The key step was selective removal of the concomitant pyranoside by enzymatic hydrolysis to purify p-nitrophenyl β-D-galactofuranoside, a promising substrate for β-D-galactofuranosidase from Streptomyces species.
- Ota, Ryo,Okamoto, Yumi,Vavricka, Christopher J.,Oka, Takuji,Matsunaga, Emiko,Takegawa, Kaoru,Kiyota, Hiromasa,Izumi, Minoru
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- Strong Inhibition of Cholera Toxin B Subunit by Affordable, Polymer-Based Multivalent Inhibitors
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Cholera is a potentially fatal bacterial infection that affects a large number of people in developing countries. It is caused by the cholera toxin (CT), an AB5 toxin secreted by Vibrio cholera. The toxin comprises a toxic A-subunit and a pentameric B-subunit that bind to the intestinal cell surface. Several monovalent and multivalent inhibitors of the toxin have been synthesized but are too complicated and expensive for practical use in developing countries. Meta-nitrophenyl α-galactoside (MNPG) is a known promising ligand for CT, and here mono- and multivalent compounds based on MNPG were synthesized. We present the synthesis of MNPG in greatly improved yields and its use while linked to a multivalent scaffold. We used economical polymers as multivalent scaffolds, namely, polyacrylamide, dextran, and hyperbranched polyglycerols (hPGs). Copper-catalyzed alkyne azide cycloaddition reaction (CuAAC) produced the inhibitors that were tested in an ELISA-type assay and an intestinal organoid swelling inhibition assay. The inhibitory properties varied widely depending on the type of polymer, and the most potent conjugates showed IC50 values in the nanomolar range.
- Haksar, Diksha,De Poel, Eyleen,Van Ufford, Linda Quarles,Bhatia, Sumati,Haag, Rainer,Beekman, Jeffrey,Pieters, Roland J.
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p. 785 - 792
(2019/02/05)
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- GLYCOSYL CERAMIDE COMPOUNDS AND PREPARATION METHOD THEREOF
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PURPOSE: A glycosylceramide compound is provided to restore damaged skin, to protect skin against external stimulus, to have an anti-aging effect, a skin-moisturizing effect, and an atopic dermatitis-treating effect, and to improve solubility. CONSTITUTION: A glycosylceramide compound is represented by chemical formula 1. In chemical formula 1, n is an integer from 1-4; each of R1, R2, and R3 is hydrogen or a glycosyl group; and each of R4 and R5 is a C1-20 alkyl group or an alkene group. A manufacturing method of the glycosylceramide compound includes a step of making a monohydroxy acetal ceramide compound represented by chemical formula 4 with a monosaccharide. In chemical formula 4, n is an integer from 1-4; each of R4 and R5 is a C1-20 alkyl group or an alkene group; each of Ra and Rb is a C1-6 alkyl group, a C6-10 aryl, or C1-6 alkyl-substituted C6-10 aryl; and X is an element from group 13 or group 14.
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Paragraph 0078; 0096; 0101-0106
(2019/08/12)
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- GLYCOCONJUGATES OF RNA INTERFERENCE AGENTS
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The present invention relates to agents, compositions and methods for inhibiting the expression of a target gene, comprising an RNAi agent bearing at least one galactosyl moiety. These are useful for delivering the gene expression inhibiting activity to c
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- Monosaccharide Analogues of Anticancer Peptide R-Lycosin-I: Role of Monosaccharide Conjugation in Complexation and the Potential of Lung Cancer Targeting and Therapy
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Glycoconjugation is a promising modification strategy for the optimization of peptide drugs. In this study, five different monosaccharide derivatives (7a-e) were covalently linked to the N-terminal of R-lycosin-I, which yielded five glycopeptides (8a-e). They demonstrated increased or reduced cytotoxicity depending on monosaccharide types, which might be explained by the changes of physicochemical properties. Among all synthesized glycopeptides, only 8a exhibited increased cytotoxicity (IC50 = 9.6 ± 0.3 μM) and selectivity (IC50 = 37.4 ± 5.9 μM). The glucose transporter 1 (GLUT1) with high expression in cancer cells was approved to be involved in the cytotoxicity and selectivity enhancement of 8a. Furthermore, 8a but not R-lycosin-I inhibited tumor growth in the nude mice xenograft model without generating side effects intraperitoneally. Taken together, this study reveals the different monosaccharide roles in peptide modification and also provides an optimized anticancer peptide with high activity and selectivity, that is, 8a might be a promising lead for developing anticancer drugs.
- Zhang, Peng,Ma, Jing,Zhang, Qianqian,Jian, Shandong,Sun, Xiaoliang,Liu, Bobo,Nie, Liqin,Liu, Meiyan,Liang, Songping,Zeng, Youlin,Liu, Zhonghua
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p. 7857 - 7873
(2019/10/11)
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- A Simple Method for the Preparation of Stainless and Highly Pure Trichloroacetimidates
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We describe a method for obtaining various allylic, benzylic, and glucosyl 2,2,2-trichloroacetimidates (TCAIs) as stainless liquids or solids at the crude stage. The general synthetic method for the preparation of TCAIs often leads to stained products, and further purification of crude TCAIs causes decomposition due to their instability. In the described method, we use a solvent that barely dissolves the reactant, providing stainless and sufficiently pure TCAIs without requiring a purification step. Furthermore, the reaction mixture is turbid at the beginning and clear at the end, allowing us to monitor the progress of the reaction visually.
- Ikeuchi, Kazutada,Murasawa, Kentaro,Yamada, Hidetoshi
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supporting information
p. 1308 - 1312
(2019/06/20)
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- Low-budget 3D-printed equipment for continuous flow reactions
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This article describes the development and manufacturing of lab equipment, which is needed for the use in flow chemistry. We developed a rack of four syringe pumps controlled by one Arduino computer, which can be manufactured with a commonly available 3D printer and readily available parts. Also, we printed various flow reactor cells, which are fully customizable for each individual reaction. With this equipment we performed some multistep glycosylation reactions, where multiple 3D-printed flow reactors were used in series.
- Neumaier, Jochen M.,Madani, Amiera,Klein, Thomas,Ziegler, Thomas
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supporting information
p. 558 - 566
(2019/03/13)
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- Biomimetic synthesis of nudicaulins i and II, yellow pigments from the Iceland poppy: Papaver nudicaule
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Indole and the anthocyanin orientalin proceed through a unique cascade sequence that leads to nudicaulins I and II in 92% yield. This biomimetic synthesis confirms the biosynthesis proposal for these structurally unprecedented flavoalkaloids that play a key role in the colour range displayed by the Iceland poppy.
- Devlin, Rory,Sperry, Jonathan
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supporting information
p. 13594 - 13597
(2019/11/14)
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- Chemical synthesis method of Bacillus pyocyaneus 011 serotype O antigen oligosaccharide
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The invention discloses a chemical synthesis method of Bacillus pyocyaneus 011 serotype O antigen oligosaccharide, and belongs to the field of chemistry. The method comprises the steps that a D-glucose block, an L-fucosamine block and a D-fucosimide block are utilized to construct O antigen trisaccharide, wherein the D-glucose block or the L-fucosamine block is connected with the D-fucosimide block through a 1,2-alpha-cis-glycosidic bond, the D-glucose block is connected with the L-fucososamine block through a 1,2-alpha-trans-glycosidic bond, and the 1,2-alpha-cis-glycosidic bond is constructed in a mixed solvent; the mixed solvent comprises two or more of dichloromethane, diethyl ether and thiophene. The method has the advantages that D-mannose is utilized as a raw material to obtain D-fucose simply, conveniently and efficiently; the uniform construction of the cis-glycosidic bond is achieved by relying on the appropriate mixed solvent; the stereoselectivity can reach 100%; and the method has a good application prospect in the development of novel drugs and vaccines for resisting Bacillus pyocyaneus and the like.
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- GLUCOSAMINE DERIVATIVES AND PHARMACEUTICAL USES THEREOF
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There are provided compounds of Formula (A) and pharmaceutically acceptable salts and esters thereof, and pharmaceutical compositions thereof, used for the prevention or treatment in a mammal of joint and bone disorders such as arthritis and osteoporosis.
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- Development of Pseudomonas aeruginosa Lectin LecA Inhibitor by using Bivalent Galactosides Supported on Polyproline Peptide Scaffolds
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LecA is a galactose-binding tetrameric lectin from Pseudomonas aeruginosa involved in infection and biofilm formation. The emergent antibiotic resistance of P. aeruginosa has made LecA a promising pharmaceutical target to treat such infections. To develop LecA inhibitors, we exploit the unique helical structure of polyproline peptides to create a scaffold that controls the galactoside positions to fit their binding sites on LecA. With a modular scaffold design, both the galactoside ligands and the inter-ligand distance can be altered conveniently. We prepared scaffolds with spacings of 9, 18, 27, and 36 ? for ligand conjugation and found that glycopeptides with galactosides ligands three helical turns (27 ?) apart best fit LecA. In addition, we tested different galactose derivatives on the selected scaffold (27 ?) to improve the binding avidity to LecA. The results validate a new multivalent scaffold design and provide useful information for LecA inhibitor development.
- Huang, Shao-Feng,Lin, Cin-Hao,Lai, Yu-Tsung,Tsai, Chia-Lung,Cheng, Ting-Jen R.,Wang, Sheng-Kai
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p. 686 - 700
(2018/03/05)
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- Probing the influence of linker length and flexibility in the design and synthesis of new trehalase inhibitors
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This work aims to synthesize new trehalase inhibitors selective towards the insect trehalase versus the porcine trehalase, in view of their application as potentially non-toxic insecticides and fungicides. The synthesis of a new pseudodisaccharide mimetic 8, by means of a stereoselective α-glucosylation of the key pyrrolizidine intermediate 13, was accomplished. The activity of compound 8 as trehalase inhibitor towards C. riparius trehalase was evaluated and the results showed that 8 was active in the μM range and showed a good selectivity towards the insect trehalase. To reduce the overall number of synthetic steps, simpler and more flexible disaccharide mimetics 9–11 bearing a pyrrolidine nucleus instead of the pyrrolizidine core were synthesized. The biological data showed the key role of the linker chain’s length in inducing inhibitory properties, since only compounds 9 (α,β-mixture), bearing a two-carbon atom linker chain, maintained activity as trehalase inhibitors. A proper change in the glucosyl donor-protecting groups allowed the stereoselective synthesis of the β-glucoside 9β, which was active in the low micromolar range (IC50 = 0.78 μM) and 12-fold more potent (and more selective) than 9α towards the insect trehalase.
- D’Adamio, Giampiero,Forcella, Matilde,Fusi, Paola,Parenti, Paolo,Matassini, Camilla,Ferhati, Xhenti,Vanni, Costanza,Cardona, Francesca
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- Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues
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Spinetoram, a mixture of spinetoram J (XDE-175-J, major component) and spinetoram L (XDE-175-L), is a new kind of fermentation-derived insecticide with a broad range of action against many insect pests, especially Cydia pomonella, Leaf miner and Thrips. Similar to spinosad, spinetoram is friendly to the environment, and non-toxic to animals and human beings. Therefore, spinetoram has been widely applied in pest control and grain storage. In a previous study, we had reported a semi-synthesis of spinetoram J. However, in that synthesis, there were more experimental steps, and the operations were troublesome. So an improved synthesis based on a self-protection strategy was designed and discussed. In this work, 3-O-ethyl-2,4-di-O-methylrhamnose was used as both the reaction substrate of C9–OH and the protecting group of C17–OH. The number of synthetic steps and costs were significantly reduced. In addition, a variety of D-forosamine replacement analogues of spinetoram J were synthesized based on the improved semi-synthesis, and their insecticidal activities were evaluated against third-instar larvae of Plutella xylostella. Although none of the analogues were as potent as spinetoram, a few of the analogues have only a 20–40 times lower activity than spinetoram. In particular, one of these analogues was approximately as active as spinosad. This study highlights the possibility of developing new insecticidal chemistries by replacing sugars on natural products with other groups, and the improved semi-synthesis will be helpful for further researches on spinetoram.
- Zhang, Kai,Li, Jiarong,Liu, Honglin,Wang, Haiyou,Lamusi
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p. 2321 - 2330
(2018/09/14)
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- NAPHTHALENE DIIMIDE COMPOUNDS FOR TREATMENT OF DISEASES
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The invention relates to novel compounds which are naphthalene diimide sugar conjugates of general formula (I) and its procedure of obtainment. The compounds of the invention are used in therapy; particularly they have shown antiproliferative, antitrypanosomal and antimalarial activity.
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- Synthesis of Oxaphosphinane-Based Pseudodisaccharides
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The synthesis of pseudodisaccharides based on an oxaphosphinane heterocycle is described. Disaccharide mimetics 5 and 6 were readily obtained through glycosylation of a hydroxy group with appropriately protected furanosyl or pyranosyl carbohydrates using
- Babouri, Rachida,Clarion, Ludovic,Rolland, Marc,Van der Lee, Arie,Kabouche, Zahia,Volle, Jean-No?l,Virieux, David,Pirat, Jean-Luc
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p. 5357 - 5369
(2017/10/06)
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- Incorporation of 'click' chemistry glycomimetics dramatically alters triple-helix stability in an adiponectin model peptide
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Adiponectin (Adpn) has been shown to be a possible therapeutic for Type II diabetes, however the production of a therapeutic version of Adpn has proved to be challenging. Biological studies have highlighted the importance of the glycosylated lysine residues for the formation of bioactive high molecular weight oligomers of Adpn. Through the use of 'click' glycopeptide mimetics, we investigated the role of glycosylated lysine and serine residues for the formation of triple helical structures of the collagenous domain of Adpn, in the context of a collagen model peptide scaffold. The physical properties of the unglycosylated lysine and serine peptides are compared with their glycosylated analogues. Our results highlight the crucial role of lysine residues for formation of the triple helical structure of Adpn, possibly due to the extension of both intra- and interstrand hydrogen bonding networks. Strikingly, we observed a significant decrease in thermal stability upon incorporation of triazole-linked analogues of glycosylated lysine residues into the adiponectin collageneous domain, indicating possible uses of 'click' glycomimetics for bioengineering applications.
- Lutteroth, Katherine R.,Harris, Paul W.R.,Wright, Tom H.,Kaur, Harveen,Sparrow, Kevin,Yang, Sung-Hyun,Cooper, Garth J.S.,Brimble, Margaret A.
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supporting information
p. 5602 - 5608
(2017/07/12)
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- Removal of some common glycosylation by-products during reaction work-up
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With the aim of improving the general glycosylation protocol to facilitate easy product isolation it was shown that amide by-products from glycosylation with trichloroacetimidate and N-phenyl trifluoroacetimidate donors could be removed during reaction work-up by washing with a basic aqueous solution. Excess glycosyl acceptor or lactol originating from glycosyl donor hydrolysis could equally be removed from the reaction mixture by derivatization with a basic tag and washing with an acidic solution during reaction work-up.
- Heuckendorff, Mads,Jensen, Henrik H.
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- Efficient synthesis and activity of beneficial intestinal flora of two lactulose-derived oligosaccharides
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Lactulose is considered as a prebiotic because it promotes the intestinal proliferation of Lactobacillus acidophilus which is added to various milk products. Moreover, lactulose is used in pharmaceuticals as a gentle laxative and to treat hyperammonemia. This study was aimed at the total synthesis of two Lactulose-derived oligosaccharides: one is 3-O-β-d-galactopyranosyl-d-fructose, d-fructose and β-d-galactose bounded together with β-1,3-glycosidic bound, the other is 1-O-β-d-galactopyranosyl-d-fructose, d-fructose and β-d-galactose bounded together with β-1,1-glycosidic bound, which were accomplished in seven steps from d-fructose and β-d-galactose and every step of yield above 75%. This synthetic route provided a practical and effective synthetic strategy for galactooligosaccharides, starting from commercially available monosaccharides. Then we evaluated on their prebiotic properties in the search for potential agents of regulating and improving the intestinal flora of human. The result showed that the prebiotic properties of Lactulose-derived oligosaccharides was much better than Lactulose. Among them, 3-O-β-d-galactopyranosyl-d-fructose displayed the most potent activity of proliferation of L. acidophilus.
- Zhu, Zhen-Yuan,Cui, Di,Gao, Hui,Dong, Feng-Ying,Liu, Xiao-Cui,Liu, Fei,Chen, Lu,Zhang, Yong-Min
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- Self-assembly of supra-amphiphile of azobenzene-galactopyranoside based on dynamic covalent bond and its dual responses
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In this paper, dynamic covalent bond has been employed to construct supra-amphiphile of carbohydrate for the first time. In neutral environment, the molecule was fabricated by reacting a hydrophobic building block bearing benzoic aldehyde with a hydrophilic building block bearing hydrazine to form a sugar-containing supra-amphiphile based on acylhydrazone bond. The obtained azobenzene-galactopyranoside (Azo-Gal) supra-amphiphile self-assembled to fibrillar structure in water, which showed dual responses to UV light and pH.
- Wang, Tian-Nan,Yang, Guang,Wu, Li-Bin,Chen, Guo-Song
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supporting information
p. 1740 - 1744
(2016/12/14)
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- Synthesis and Properties of Alkyl β-d-Galactopyranoside
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A series of alkyl β-d-galactopyranosides were prepared by the trichloroacetimidate method with d-galactose and alcohols with different chain lengths as raw materials. Their solubility, surface tension, emulsification, foaming, wettability, thermotropic liquid crystalline properties, and thermal stability were investigated. Alkyl β-d-galactopyranosides are soluble in water and ethanol, and the solubility decreases with increasing alkyl chain length. Decyl β-d-galactopyranoside was insoluble in water, but soluble in ethanol. Dissolution of alkyl β-d-galactopyranoside in water is an endothermic process with dissolution enthalpies greater than zero. Nonyl β-d-galactopyranoside had an excellent emulsifying?property, better foaming ability and the best foam stability. The CMC values of alkyl β-d-galactopyranosides decrease with increasing of alkyl chain length. Alkyl β-d-galactopyranosides are thermally stable up to 270?°C. Alkyl β-d-galactopyranosides show the distinctive optical texture of a thermotropic liquid crystal smectic A type phase. Decyl β-d-galactopyranoside showed the strongest wettability.
- Chen, Guoyong,Li, Zhencao,Chen, Langqiu,Ji, Shanwei,Shen, Wangzhen
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p. 1095 - 1105
(2016/10/18)
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- Synthesis of dihydrosterculic acid-based monoglucosyl diacylglycerol and its analogues and their biological evaluation
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In the present study, Lactobacillus plantarum glycolipid (GL1) molecule in β-configuration and its fatty acid analogues were synthesized using trichloroacetimidate methodology. The β-configuration of the GL1 molecule was unambiguously assigned by NMR studies using 2D-ROESY (NOE) and J-coupling analysis. Dihydrosterculic acid was synthesized using Furukawa's reagent and the selective esterification of dihydrosterculic acid at C-3 position of glycerol was achieved with EDC-HCl at 0 °C. In vitro cytotoxicity of the GL1 molecule and its fatty acid analogues was evaluated against DU145, A549, SKOV3 and MCF7 cell lines. Among all the synthesized molecules, the GL1 molecule and compound 7d showed moderate activity, while the compound 7b showed promising activity against all the tested cell lines with IC50 values of 20.1, 18.2, 19.1 and 17.6 ?1/4M, respectively. In addition, all tested compounds showed poor cytotoxicity against normal HUVEC cells. The MCF7 cells when treated with compound 7b showed lower bromodeoxyuridine incorporation levels as compared to untreated cells, suggesting that the compound 7b was highly effective and inhibited the cell proliferation. In addition, the compounds showed significant increase in caspases 3 and 9 levels by inducing apoptosis in MCF 7 cells.
- Srikanth, Vudhgiri,Prasad,Poornachandra,Phani Babu,Ganesh Kumar,Jagadeesh,Jala, Ram Chandra Reddy
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p. 134 - 145
(2016/01/16)
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- Design, synthesis and in vitro evaluation of d-glucose-based cationic glycolipids for gene delivery
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A cationic lipid consists of a hydrophilic headgroup, backbone and hydrophobic tails which have an immense influence on the transfection efficiency of the lipid. In this paper, two novel series of cationic cyclic glycolipids with a quaternary ammonium headgroup and different-length hydrophobic tails (dodecyl, tetradecyl, hexadecyl) have been designed and synthesized for gene delivery. One contains lipids 1-3 with two hydrophobic alkyl chains linked to the glucose ring directly via an ether link. The other contains lipids 4-6 with two hydrophobic chains on the positively charged nitrogen atoms. All of the lipids were characterized for their ability to bind to DNA, size, ζ-potential, and toxicity. Atomic force microscopy showed that the lipids and DNA-lipid complexes were sphere-like forms. The lipids were used to transfer enhanced green fluorescent protein (EGFP-C3) to HEK293 cells without a helper lipid, the results indicated that lipids 4-6 have better transfection efficiency, in particular lipids 5-6 have similar or better efficiency, compared with the commercial transfection reagent lipofectamine 2000.
- He, Chengxi,Wang, Shang,Liu, Meiyan,Zhao, Chunyan,Xiang, Shuanglin,Zeng, Youlin
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p. 1611 - 1622
(2016/02/09)
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- Glucose derivative cationic liposome method for preparing nano-particles (by machine translation)
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The invention discloses glucose derivative cationic liposome method for the preparation of nano-particles. Using glucose as the raw material, a series of different structure to synthesize the glucose derivative cationic lipid: Di -C 12-Glu-TMA, Di -C 12-Glu-TMA, Di -C 12-Glu-TMA, Di -C 12-Glu-TMA, Glu-DiC 12 MA, Glu-DiC 14 MA, Glu-DiC 16 MA and Glu-DiC 18 MA. The above-mentioned liposome through the water dispersion to obtain a good structure stability, moderate size particle size, particle size distribution is narrow, the surface charge is moderate, the preparation cost is low glucose derivative cationic liposome nanoparticle, can realize the nucleic acid drug from butcher outside to intracellular transit, can also be used for non-nucleate drug transfer carrier. (by machine translation)
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- An efficient and practical preparation of a potent low-affinity na+-dependent glucose cotransporter (SGLT2) inhibitor, sergliflozin etabonate
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The development of an efficient and practical process for the preparation of Sergliflozin etabonate (1), a prodrug of a novel selective low-affinity Na+-dependent glucose cotransporter (SGLT2) inhibitor, Sergliflozin (2), is described. Its development required a suitable process for large-scale manufacturing. We established a chromatography-free approach for 2-[(4-methoxyphenyl)methyl]phenol (5), the efficient O-glycosylation of 5 with penta-O-acetyl-β-D-glucopyranose (7) without using a trichloroacetimidate intermediate (9), and efficient reaction conditions to introduce an ethoxycarbonyl group onto the primary alcohol of 2 with high selectivity. This process provided 1 with a 45% overall yield from anisole (10).
- Kobayashi, Masahiro,Isawa, Hidetoshi,Sonehara, Junichi,Kubota, Minoru
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p. 1599 - 1613
(2016/10/12)
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- Bisindolyl maleimide derivative and preparation method and application thereof
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The invention provides a bisindolyl maleimide derivative and a preparation method and application thereof. The bisindolyl maleimide derivative has an excellent alpha-glucosidase inhibition effect and can be used for preventing and treating diabetes.
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- Bisindolylmaleimide derivative, and preparation method and use thereof
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The invention provides a bisindolylmaleimide derivative, and a preparation method and a use thereof. The bisindolylmaleimide derivative has a good tumor treatment effect, especially has a good treatment effect on some drug-resistant tumors, and can realize accurate treatment of the drug-resistant tumors.
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- Novel galactosylated poly(ethylene glycol)-cholesterol for liposomes as a drug carrier for hepatocyte-targeting
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In this study, three types of galactosylated cholesterol (i.e., gal-PEG194-chol, gal-PEG1000-chol and gal-PEG2000-chol) were synthesized with one terminal of polyethylene glycol of various chain lengths conjugated to the galactoside moiety, and the other terminal conjugated to the cholesterol. The galactose-modified liposomes were prepared by thin film-hydration method and doxorubicin (DOX) was loaded to the liposomes by using a ammonium sulfate gradient procedure. The liposomal formulations with galactosylated cholesterol were characterized. Flow cytometry and laser confocal scanning microscopy analyses showed that the galactose-modified liposomes facilitated the intracellular uptake of liposomes into HepG2 via asialoglycoprotein receptor (ASGP-R) mediated endocytosis. Cytotoxicity assay showed that the cell proliferation inhibition effect of galactosemodified liposomes was higher than that of the unmodified liposomes. Additionally, the study on frozen section of liver showed that the galactose-modified liposomes enhanced the intracellular uptake of liposomes into hepatocytes. Taken together, these results suggested that liposomes containing such galactosylated cholesterol (i.e., gal-PEG-chol), had a great potential as drug delivery carriers for hepatocyte-selective targeting.
- Zhang, Huafang,Xiao, Yan,Cui, Shengmiao,Zhou, Yuefang,Zeng, Ke,Yan, Mina,Zhao, Chunshun
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p. 4058 - 4069
(2015/03/05)
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- Fluorous-based carbohydrate Quartz Crystal Microbalance
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Fluorous chemistry has brought many applications from catalysis to separation science, from supramolecular materials to analytical chemistry. However, fluorous-based Quartz Crystal Microbalance (QCM) has not been reported so far. In the current paper, fluorous interaction has been firstly utilized in QCM, and carbohydrate-protein interaction and carbohydrate-carbohydrate interaction have been detected afterward.
- Chen, Lei,Sun, Pengfei,Chen, Guosong
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supporting information
p. 66 - 69
(2015/03/14)
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- GLYCOLIPIDS AND PHARMACEUTICAL COMPOSITIONS THEREOF FOR USE IN THERAPY
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A compound of Formula I: R1 -L1 -C(A)(A') - CH2, - L2-R2 or a pharmaceutically acceptable salt thereof, for use in medicine, for example in the treatment of a disease or condition selected from the group comprising cancer, autistic spectrum disorders. Alzheimer' s disease, Parkinson's disease, Huntingdon' s disease, muscie wasting and viral infection, wherein: R1 is selected from a carbohydrate group or derivative thereof, hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an aikenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; L1 is a linking group; L2 is a linking group; R2 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; A is selected from hydrogen and a C1 -C6 alkyl group: A' is selected from hydrogen, a C3 -C6 alkyl group, and L3-R3; wherein L3 is a linking group; and R3 is selected from hydrogen, a C1-C24 alkyl or a C1-C24 derivative of an alkyl group, a C2-C24 alkenyl or a C2-C24 derivative of an alkenyl group, and a C2-C24 alkynyl group or a C2-C24 derivative of an alkynyl group; and wherein if A' is not L3-R3, then R2 is a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group; and wherein if A' is L3-R3, then one or both of R2 and R3 are a C10-C24 alkyl or a C10-C24 derivative of an alkyl group, a C10-C24 alkenyl or a C10-C24 derivative of an alkenyl group, or a C10-C24 alkynyl group or a C10-C24 derivative of an alkynyl group.
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Page/Page column 77
(2015/11/02)
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- 3-(Dimethylamino)-1-propylamine: A cheap and versatile reagent for removal of byproducts in carbohydrate chemistry
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Inexpensive 3-(dimethylamino)-1-propylamine (DMAPA) was found to be effective in anomeric deacylation reactions giving 1-O deprotected sugars in high yield as precursors for the formation of imidate glycosyl donors. DMAPA was also found to be useful for removing excess reagents such as benzoyl chloride, tosyl chloride, and 2,2,2-trifluoro-N-phenylacetimidoyl chloride. The deacylation reaction could be conducted in moist THF and did not require chromatographic purification since an acidic wash was sufficient to remove excess reagent and the formed byproduct.
- Andersen, Sofie Meng,Heuckendorff, Mads,Jensen, Henrik H.
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supporting information
p. 944 - 947
(2015/04/14)
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- CARBOHYDRATE-BASED COMPOSITIONS AND METHODS FOR TARGETED DRUG DELIVERY
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Provided herein are compositions and methods for intracellular delivery. The compositions are polymer compositions in which the polymer serves as a carrier for therapeutic and/or diagnostic agents. The polymer compositions are effective in targeted delivery of therapeutic and/or diagnostic agents to a cell. The polymer compositions include a targeting moiety that includes carbohydrate groups that effectively target specific cell surface receptors. The polymer compositions also include an agent binding moiety that effectively associates the therapeutic and/or diagnostic agent to be delivered to the cell.
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Paragraph 0150
(2014/09/03)
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