- Preparation of enantiomerically pure fructose-derived 1,3-oxazin-2-one by INIR methodology and its application as a chiral auxiliary in some model asymmetric reactions
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A newly developed fructose-based homochiral 1,3-oxazin-2-one reagent prepared via a regioselective and stereoselective intramolecular nitrene insertion reaction (INIR) exerts smooth stereocontrol resulting in high levels of asymmetric induction and chemical yield in various synthetic transformations including aldol, Diels-Alder cycloaddition and α-bromination reactions.
- Banks, Malcolm R.,Cadogan,Gosney, Ian,Gould, Robert O.,Hodgson, Philip K. G.,McDougall, Douglas
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- 2,3:4,5-DI-O-isopropylidene-β-D-fructopyranose as chiral auxiliary in asymmetric α-alkylation of ester enolates
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The asymmetric α-alkylation of enolates of chiral esters derived from 2,3:4,5-di-O-isopropylidene-β-D-fructopyranose (1) was studied. The diastereoselectivities range from 1:1 to 7:3. The absolute stereochemistry of the major S-isomers were established by chemical correlation. The diastereoselectivities of the alkylated products were similar to those observed in the deprotonation steps. The stereochemical outcome can be interpreted by an intramolecular complexation of the lithium cation of the carbohydrate ester enolates.
- Costa, Paulo R.R.,Ferreira, Vitor F.,Alencar, Karla G.,Filho, Hiran C.A.,Ferreira, Claudio M.,Pinheiro, Sergio
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- Structure-sweetness relationships for fructose analogs. Part I. Synthesis and evaluation of sweetness of 5-deoxy-D-threo-hexulose
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5-Deoxy-D-threo-hexulose ("5-deoxyfructose", "5-deoxysorbose") has been prepared in six steps from D-fructose.The reaction of 2,3-O-isopropylidene-β-D-fructopyranose with sulfuryl chloride afforded exclusively 5-chloro-5-deoxy-2,3-O-isopropylidene-α-L-sorbopyranose in the key step. "5-Deoxyfructose" exists only in the 2C5(D) pyranoid form in solution, and was found to be much sweeter than L-sorbose and nearly as sweet as D-fructose.Comments on this unexpected sweetness result are given.
- Martin, Olivier R.,Korppi-Tommola, Sirkka-Liisa,Szarek, Walter A.
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- Synthesis and sensory characterization of novel umami-tasting glutamate glycoconjugates
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Two glycoconjugates of glutamic acid, namely, the N-glycoside dipotassium N-(D-glucos-1-yl)-L-glutamate (1) and the corresponding Amadori compound N-(1-deoxy-D-fructos-1-yl)-L-glutamic acid (2), have been synthesized in yields of 35 and 52%, respectively, using new Maillard-mimetic approaches, and their chemical structures have unequivocally been elucidated by 1D- and 2D-NMR and MS experiments. Systematic sensory studies revealed that both glycoconjugates exhibit pronounced umami-like taste with recognition taste thresholds of 1-2 mmol/L, close to that of monosodium glutamate (MSG). Contrary to an aqueous solution of MSG, 1 does not show the sweetish and slightly soapy by-note, but evokes an intense umami taste. Aqueous solutions of 2 were described by the descriptors umami, seasoning, and bouillon-like. Added to a bouillon base, which did not contain any taste enhancers, both glycoconjugates imparted a distinct umami character similar to the control sample containing the same amount of MSG on a molar basis. To the best of our knowledge, these types of glycoconjugates in general and, in particular, N-glucosyl glutamate and N-deoxyfructosyl glutamate have never been reported as taste active compounds having umami-like properties. Therefore, 1 and 2 represent a new class of umami-type taste compounds showing properties similar to the umami reference compound MSG. Systematic 13C NMR measurements revealed that 1 was fairly stable in aqueous solutions under alkaline conditions (pH 8-10) as well as in dry form. However, it rapidly hydrolyzes in neutral and acidic solutions, giving rise to glucose and glutamate. In contrast, glycoconjugate 2 was observed to be rather stable in aqueous solution as well as in the presence of human saliva.
- Beksan, Ersan,Schieberle, Peter,Robert, Fabien,Blank, Imre,Fay, Laurent Bernard,Schlichtherle-Cerny, Hedwig,Hofmann, Homas
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- Biodegradable Glycopolymeric Micelles Obtained by RAFT-controlled Radical Ring-Opening Polymerization
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The design and synthesis of an entirely degradable glycopolymer micelle was presented. This design relies on the utilization of RAFT-controlled radical ring-opening polymerization (rROP) technique to afford multiple insertions of cleavable ester linkages onto the backbone of the corona. RAFT polymerization using a macroRAFT agent based on poly(μ-caprolactone) PCL was employed to control the polymerization of well-defined statistical glycopolymers of 1-O-acryloyl-2,3:4,5-di-O-isopropylidene-β-d-fructopyranose (1-O-AiPrFru) and 5,6-benzo-2-methylene-1,3-dioxepane (BMDO) monomer. Three block copolymers were synthesized to generate poly(μ-caprolactone)-b-poly[(1-O-acryloyl-2,3:4,5-di-O-isopropylidene-β-d-fructopyranose)-co-(5,6-benzo-2-methylene-1,3-dioxepane)] (PCL-b-P[(1-O-AiPrFru)-co-(BMDO)]) with varying block lengths. Self-assembly of the deprotected block copolymers generated nonspherical egg shaped micelles, where the shorter chains PCL106-b-P[(1-O-AFru)69-co-(BMDO)9] underwent self-assembly forming micelles with the hydrodynamic diameter (DH) of 106 nm. The biodegradation of these micelles were investigated via enzymatic degradation by Lipase Pseudomonas sp., indicating entirely degradable architectures, which are no longer visible via dynamic light scattering (DLS). SEC further confirmed the appearance of fragmented glycopolymeric units. In vitro cell proliferation assay of the micelles and their degradation products revealed no toxicity against healthy human fibroblast HS27 and breast cancer MDA-MB-231 cell lines. The polymer concentration range tested was up to 0.20 mg·mL-1 with the cell viabilities of ≥95%.
- Ganda, Sylvia,Jiang, Yanyan,Thomas, Donald S.,Eliezar, Jeaniffer,Stenzel, Martina H.
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- Enhanced Antimetastatic Activity of the Ruthenium Anticancer Drug RAPTA-C Delivered in Fructose-Coated Micelles
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The ruthenium complex—dichlororuthenium (II) (p-cymene) (1,3,5-triaza-7-phosphaadamantane) (RAPTA-C)—has shown to be remarkably effective at suppressing the growth of solid tumor metastases. However, poor delivery efficacy and the lack of targeting ability of the common drug delivery system pose significant obstacles to maximize the therapeutic benefit of RAPTA-C. Inspired by the overexpression of GLUT5 transporter on the surface of breast cancer tissues but not the healthy mammary tissues, the use of d-fructose as the targeting moiety of the drug carrier can significantly improve the cellular uptake of nanoparticles, thus further enhancing the therapeutic efficiency of RAPTA-C. In this work, fructose-micelles and 2-hydroxyethyl acrylate (HEA)-micelles are prepared to investigate the difference in cellular uptake. It is found that glycopolymer leads to an increased uptake by breast cancer cells, while the HEA-micelles show less uptake. This behavior is also reflected by the slightly faster movement of fructose-coated micelles in MCF-7 tumor spheroid models using light sheet microscopy as analytical tool. The incorporation of RAPTA-C into micelles can enhance the inhibitory effect of the ruthenium drug demonstrated using invasion, chemotaxis, and haptotaxis assays. As a result, fructose-coated nanoparticles can be a promising drug delivery platform of RAPTA-C for the treatment of metastatic breast cancer. (Figure presented.).
- Lu, Mingxia,Chen, Fan,Noy, Janina-Miriam,Lu, Hongxu,Stenzel, Martina H.
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- Lipase-catalyzed esterification of steric hindered fructose derivative by continuous flow and batch conditions
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The lipase catalyzed sugar ester synthesis is an interesting strategy for producing biodegradable, non-ionic surfactants. The main disadvantage of this protocol is the long reaction time required for achieving moderated to good yields. Here, we report the esterification of steric hindered fructose derivative where important variables for batch conditions were identified by the use of a RSM protocol and then translated to the continuous flow regime with high conversions and short residence times.
- Sutili, Felipe K.,Ruela, Halliny S.,Leite, Selma G.F.,Miranda, Leandro S. De M.,Leal, Ivana C.R.,De Souza, Rodrigo O.M.A.
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- Synthesis and biological evaluation of some 6-substituted purines
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We report herein the synthesis and the in vitro antileishmanial evaluation of a series of 6-substituted purines. The most active compounds against Leishmania amazonensis promastigotes were 6-(3′-chloropropylthio)purine 2 (D.A. Benson, I. Karsch-Mizrachi, D.J. Lipman, J. Ostell, B.A. Rapp, D.L. Wheeler, Genbank. Nucleic Acids Res. 28 (2000) 15-18; E.V. Aleksandrova, P.M.I.E. Valashek, J. Med. Pharm. Chem. 35 (2001) 172-173), 6-(3′-(thioethylamine)propylthio)purine 5, 6-(α-aceticacidthio)purine 7 and 6-(6′-deoxy-1′-O-methyl-β-d-ribofuranose)purine 14 with an IC50 = 50, 50, 39 and 29 μM, respectively.
- Braga, Fernanda Gambogi,Coimbra, Elaine Soares,de Oliveira Matos, Magnum,Lino Carmo, Arturene Maria,Cancio, Marisa Damato,da Silva, Adilson David
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- A mild acetolysis procedure for the regioselective removal of isopropylidene in di-O-isopropylidene-protected pyranoside systems
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A mild acetolysis method for the regioselective removal of isopropylidene group from di-O-isopropylidene-protected hexopyranosides is reported. O-Isopropylidene-protected intermediates play an important role in carbohydrate chemistry, as they are often found in commercially available furanosyl and pyranosyl materials, and some of them contain more than one O-isopropylidene groups. Methods that permit regioselective removal of O-isopropylidene groups are extremely valuable, as the number of steps in the total synthesis of complex oligosaccharides could be significantly decreased. Here we report that trifluoroacetic acid (TFA)/acetic anhydride (Ac2O) can be used to regioselectively convert one of the two O-isopropylidene groups to vicinal di-O-acetates in the di-O-isopropylidene-protected galacto- and fructo-pyranosyl systems, and the reagent is compatible with some common functionalities such as sulfonate esters, bromide, azide etc.
- Zhang, Pengfei,Ling, Chang-Chun
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- Radiolabeling and in vitro evaluation of a new 5-fluorouracil derivative with cell culture studies
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The clinical impact and accessibility of 99mTc tracers for cancer diagnosis would be greatly enhanced by the availability of a new, simple, and easy labeling process and radiopharmaceuticals. 5-Fluorouracil is an antitumor drug, which has played an important role for the treatment of breast carcinoma. In the present study, a new derivative of 5-Fluorouracil was synthesized as (1-[{1′-(1′′-deoxy-2′′,3′′:4′′,5′′-di-O-isopropylidene-β-D-fructopyranose-1′′-yl)-1′H-1′,2′, 3′-triazol-4′-yl}methyl]-5-fluorouracil) (E) and radiolabeled with 99mTc. It was analyzed by radio thin layer chromatography for quality control and stability. The radiolabeled complex was subjected to in vitro cell-binding studies to determine healthy and cancer cell affinity using HaCaT and MCF-7 cells, respectively. In addition, in vitro cytotoxicity studies of compound E were performed with HaCaT and MCF-5 cells. The radiochemical purity of the [99mTc]TcE was found to be higher than 90% at room temperature up to 6 hours. The radiolabeled complex showed higher specific binding to MCF-7 cells than HaCaT cells. IC50 values of E were found 31.5 ± 3.4 μM and 20.7 ± 2.77 μM for MCF-7 and HaCaT cells, respectively. The results demonstrated the potential of a new radiolabeled E with 99mTc has selective for breast cancer cells.
- Ilem-Ozdemir, Derya,Atlihan-Gundogdu, Evren,Ekinci, Meliha,Halay, Erkan,Ay, Kadir,Karayildirim, Tamer,Asikoglu, Makbule
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- Synthesis and in?vitro Bioactivity Evaluation of New Galactose and Fructose Ester Derivatives of 5-Aminosalicylic Acid
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Inflammatory bowel disease (IBD) is the main risk factor for developing colorectal cancer which is common in patients of all ages. 5-Aminosalicylic acid (5-ASA), structurally related to the salicylates, is highly active in the treatment of IBD with minor side effects. In this study, the synthesis of galactose and fructose esters of 5-ASA was planned to evaluate the role of glycoconjugation on the bioactivity of the parent drug. The antibacterial activity of the new compounds were evaluated against two Gram-negative and two Gram-positive species of bacteria, with a notable effect observed against Staphylococcus aureus and Escherichia coli in comparisons with the 5-ASA. Cytotoxicity testing over HT-29 and 3T3 cell lines indicated that the toxicity of the new products against normal cells was significantly reduced compared with the original drug, whereas their activity against cancerous cells was slightly decreased. The anti-inflammatory activity test in RAW264.7 macrophage cells indicated that the inhibition of nitric oxide by both of the monosaccharide conjugated derivatives was slightly improved in comparison with the non-conjugated drug.
- Yousefi, Samira,Bayat, Saadi,Rahman, Mohd Basyaruddin Abdul,Ibrahim, Zalikha,Abdulmalek, Emilia
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- The Effect of Drug Loading on Micelle Properties: Solid-State NMR as a Tool to Gain Structural Insight
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The present study highlights the importance of understanding the structural changes of micelles induced by drug loading on their physico-chemical properties. A block copolymer with attached fructose, which interacts with GLUT5 receptor, was used and conjugated with a low and a high amount of platinum drugs. Against expectations, the low-loading micelle, despite having a less defined morphology and larger nanoparticle size according to TEM, displays higher cellular uptake and higher toxicity. This behaviour can only be understood when elucidating additional information on the structure of micelles. Extensive solid-state NMR measurements were therefore employed to reveal that the drug loading affected swelling and mobility of core and shell of the micelle. The results obtained from solid-state NMR spectroscopy could explain all the observations on this system. In summary, solid-state NMR spectroscopy is an excellent tool to understand the effects of drug loading on the behavior of micelles.
- Callari, Manuela,De Souza, Paul L.,Rawal, Aditya,Stenzel, Martina H.
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- The first general protocol for N-monoalkylation of sulfamate esters: Benign synthesis of N-alkyl Topiramate (anticonvulsant drug) derivatives
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A novel protocol for the highly selective N-monoalkylation of the sulfamate ester moiety has been developed. This reaction proceeded efficiently using alkyl halides, benzyl halides and -halo ketones as the electrophile in the presence of KF-Al2O3 as a cost-effective and robust catalyst. This approach provides new access to N-monoalkylated Topiramate (anticonvulsant drug) derivatives which are potentially of great importance in medicinal chemistry.
- Saeidian, Hamid,Abdoli, Morteza
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- An Expedient Method for Kinetically Controlled Acetonide Formation from d-Fructose Induced by Ionic Liquid Catalyst Accompanied with SrCl2·6H2O
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Abstract: The present work was undertaken to ascertain whether IL-metal salt catalyzed isopropylidenation of d-fructose yield desired acetonides. For the first time, an imidazole based ionic liquid compound accompanied with strontium chloride has been identified as a suitable dual catalyst system for the chemoselective O-isopropylidenation of d-fructose with acetone. In the present protocol, mainly the kinetically controlled less stable cyclic ketal 1,2;4,5-di-O-isopropylidene-β-d-fructopyranose is formed as an initial product with satisfactory yield and without isomerization to the thermodynamically more stable cyclic ketal 2,3;4,5-di-O-isopropylidene-β-d-fructopyranose. Therefore, this protocol is more advantageous compared to other mineral acid catalyzed protocols that require more sensitive reaction conditions. Graphic Abstract: [Figure not available: see fulltext.]
- Y?ld?r?m, Ayhan
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- Hydrate of 2,3:4,5-di-O-isopropylidene-β-D-arabino-hexos-2-ulo-2,6-pyranose as new crystalline reagent in the preparation of Amadori derived peptides
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We established, that crystalline hydrate of 2,3:4,5-di-O-isopropylidene-β-D-arabino-hexos-2-ulo-2,6-pyranose is a new, convenient and stable reagent for solid phase synthesis of peptide derived Amadori products. The structure of the title compound was studied by X-ray analysis, NMR spectroscopy, and high resolution ESI-MS. The crystal structure indicated the existence of two symmetry-independent molecules that were not connected with hydrogen bonds. A comparison with previously reported 2,3:4,5-di-O-isopropylidene-β-D-fructopyranose revealed, that these two compounds are isostructural. Versita Warsaw and Springer-Verlag Berlin Heidelberg.
- Stefanowicz, Piotr,Batorska, Joanna,Kijewska, Monika,Bartosz-Bechowski, Hubert,Szewczuk, Zbigniew,Lis, Tadeusz
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- Glycoamine Amadori derivative as well as preparation method and application thereof
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The invention relates to the technical field of Amadori derivatives, provides a glycosamine Amadori derivative, and specifically defines the structural formula of the glycosamine Amadori derivative, and the structural formula of the glycosamine Amadori derivative comprises the glycosamine Amadori derivative with three structures obtained by reaction of three different amino-acid esters and fructose. The glycosamine Amadori derivative with the three structures can be subjected to pyrolysis under the heating condition, multiple products are obtained through pyrolysis, and the pyrolysis products are stable in chemical property, lasting in effect and high in aroma quality and can be used for improving the quality of cigarettes. Experimental results show that the glycosamine Amadori derivative provided by the invention can be pyrolyzed into various products with fragrance, and can bring more harmonious mouth feel during cigarette panel test, so that the smoking quality is improved.
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Paragraph 0064; 0083-0084
(2021/06/09)
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- Crystal form of 2,3:4,5-di-O-(1-methylethylidene)-beta-D-fructopyranose chlorosulphate
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The invention belongs to the technical field of pharmaceuticals, and particularly relates to a crystal form A of 2,3:4,5-di-O-(1-methylethylidene)-beta-D-fructopyranose chlorosulphate. The invention further relates to a preparation method of the 2,3:4,5-di-O-(1-methylethylidene)-beta-D-fructopyranose chlorosulphate and the purpose of the 2,3:4,5-di-O-(1-methylethylidene)-beta-D-fructopyranose chlorosulphate to preparation of Topiramate. The crystal form A of the prepared 2,3:4,5-di-O-(1-methylethylidene)-beta-D-fructopyranose chlorosulphate is high in purity, single-impurity 2,3:4,5-di-O-(1-methylethylidene)-beta-D-fructopyranose is smaller than 0.11%, the yield of the Topiramate prepared from the crystal form A of the 2,3:4,5-di-O-(1-methylethylidene)-beta-D-fructopyranose chlorosulphateis 92% or above, the HPLC purity is greater than 99.90%, the single-impurity 2,3:4,5-di-O-(1-methylethylidene)-beta-D-fructopyranose is smaller than 0.03%, and single impurities of a condensation compound are smaller than 0.05%.
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Paragraph 0073-0075
(2020/01/25)
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- The effect of solvents on the thermal degradation products of two Amadori derivatives
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To enrich the flavor additives of the Maillard reaction, two Amadori analogs, N-(1-deoxy-d-fructosyl-1-yl)-l-phenylalanine ester (Derivative 1) and di-O-isopropylidene-2,3:4,5-?-d-fructopyranosyl phenylalanine ester (Derivative 2), were chemically synthes
- Li, Rui,Zhang, Shiyi,Zhang, Yudan,Zhao, Mingqin
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p. 9309 - 9317
(2020/03/23)
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- Fructose modified breast cancer targeting lipid material, and preparation method and applications thereof
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The invention discloses a novel lipid material used for realizing breast cancer targeting medicine delivery and prolonging medicine acting time. According to the novel lipid material, endogenous cholesterol is subjected to modification, a joining chain is adopted, and connection with fructose with breast cancer targeting function is carried out, so that ligand molecules with breast cancer targeting function are prepared; the ligand molecules are adopted for modification of a lipid material, so that the affinity of the novel lipid material with acceptors is increased, better tumor targeting performance is achieved, and better breast cancer treatment effect is achieved. The novel lipid material can be used in different dosage forms including liposome, nanoparticle, and micelle, prepared Paclitaxel loaded liposome possesses obvious breast cancer targeting performance; and the application prospect is promising.
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Paragraph 0018
(2019/08/20)
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- Fructose and RGD peptide co-modified dual-targeting triple-negative breast cancer lipid material
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The present invention discloses a novel lipid material for realizing transfer of triple negative breast cancer targeted drugs. The novel lipid material takes lysine as a connecting group to respectively connect a cholesteric part, a fructose part and an RGD part. Affinities between fructose in the novel lipid material and a fructose transporter GLUT5, and between RGD in the novel lipid material and an integrin receptor alpha v beta 3 are respectively utilized to realize double targeting functions of the triple negative breast cancer and exert stronger targeted treatment effects on the triple negative breast cancer. The novel liquid material can be sued for different dosages of liposomes, nanoparticles, micelle, etc. A prepared paclitaxel-loaded liposome has obvious triple negative breast cancer targeting property and a wide application prospect.
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Paragraph 0019
(2019/12/15)
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- Dual-targeting liposomes with active recognition of GLUT5 and αvβ3 for triple-negative breast cancer
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At present, chemo- and radiotherapies remain to be the mainstream methods for treating triple-negative breast cancer (TNBC), which is known for poor prognosis and high rate of mortality. Two types of novel dual-targeting TNBC liposomes (Fru-RGD-Lip and Fru+RGD-Lip) that actively recognize both fructose transporter GLUT5 and integrin αvβ3 were designed and prepared in this work. Firstly, a Y-shaped Fru-RGD-chol ligand, where a fructose and peptide Arg-Gly-Asp (RGD) were covalently attached to cholesterol, was designed and synthesized. Then, the Fru-RGD-Lip was constructed by inserting Fru-RGD-chol into liposomes, while Fru+RGD-Lip was obtained by inserting both Fru-chol and RGD-chol (with the molar ratio of 1:1) into liposomes. The particle size, zeta potential, encapsulation efficiency and serum stability of the paclitaxel-loaded liposomes were characterized. The results indicated that the paclitaxel-loaded Fru-RGD-Lip had the strongest growth inhibition against GLUT5 and αvβ3 overexpressed MDA-MB-231 and 4T1 cells. The cellular uptake of Fru-RGD-Lip on MDA-MB-231 cells and 4T1 cells was 3.19- and 3.23-fold more than that of the uncoated liposomes (Lip). The uptake of Fru+RGD-Lip was slightly lower, giving a 2.81- and 2.90-fold increase than that of Lip in two cell lines, respectively. The mechanism study demonstrated that the cellular uptake of both dual-targeting liposomes was likely to be recognized and mediated by GLUT5 and αvβ3 firstly, then endocytosed through comprehensive pathways in an energy-dependent manner. Moreover, Fru-RGD-Lip displayed the maximum accumulation, which was 2.62-fold higher than that of Lip for instance, at the tumor sites compared to other liposomes using in vivo imaging. Collectively, the liposomes co-modified by fructose and RGD have enormous potential in the development of targeted TNBC treatment, especially the covalently modified Fru-RGD-Lip, making it a promising multifunctional liposome.
- Pu, Yanchi,Zhang, Hao,Peng, Yao,Fu, Qiuyi,Yue, Qiming,Zhao, Yi,Guo, Li,Wu, Yong
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- A Green and Sustainable Route to Carbohydrate Vinyl Ethers for Accessing Bioinspired Materials with a Unique Microspherical Morphology
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Synthesizing chemicals and materials from renewable sources is one of the main aims of modern science. Carbohydrates represent excellent renewable natural raw materials that are ecofriendly, inexpensive, and biologically compatible. A green procedure has been developed for the vinylation of carbohydrates by using readily available calcium carbide. Various carbohydrates were utilized as starting materials, resulting in mono-, di-, and tetravinyl ethers in high to excellent yields (81–92 %). The synthesized biobased vinyl ethers were utilized as monomers in free radical and cationic polymerizations. A unique combination of a smooth surface and intrinsic microcompartments was achieved in the synthesized materials. Two types of biobased materials were prepared involving microspheres and intrinsic hollow compartments in polymers. Scanning electron microscopy with built-in ion beam cutting was applied to reveal the spatial hierarchical structures in 3D space.
- Rodygin, Konstantin S.,Werner, Irina,Ananikov, Valentine P.
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p. 292 - 298
(2017/12/26)
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- Preparation method of high-purity topiramate
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The invention discloses a preparation method of high-purity topiramate. The preparation method comprises the following steps: (1) performing reflux reaction on D-fructose and acetone in a dehydratingagent, centrifuging, then performing low-temperature reaction under a 4A molecular sieve-sulfuryl chloride-acid binding agent system, filtering and performing organic layer vacuum distillation; (2) dissolving a reaction product obtained in the step (1) by using a solvent, then introducing ammonia gas, stirring for 4-8 hours at a room temperature, vacuum-pumping for 0.5 h, increasing the temperature of reaction liquid, refluxing for 1 h, then slowly reducing the temperature to below 10 DEG C, crystallizing for 4 h, centrifuging and washing a filter cake with a solvent; (3) pressurizing a reaction product obtained in the step (2), increasing the temperature and dissolving, reducing the temperature to 65 DEG C, adding a small amount of topiramate seed crystals with a respective purity of morethan 99 percent, continuously reducing the temperature to 5 DEG C, crystallizing for 6 h, centrifuging and washing a filter cake with a low-temperature solvent to obtain the high-purity topiramate. The topiramate produced by the preparation method disclosed by the invention has the advantages of being abundant and cheap in raw material, low in cost, high in yield, high in purity, great in industrial value, low in pollution and the like.
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Paragraph 0019; 0023; 0025; 0028; 0030; 0033; 0035
(2018/09/08)
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- Practical preparation of mono- and di-O-isopropylidene derivatives of monosaccharides and methyl 4,6-O-benzylidene glycosides from free sugars in a deep eutectic solvent
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Free sugars were rapidly converted into the corresponding di-O-isopropylidene derivatives and methyl O-benzylidene glycosides in excellent yields and purity in a deep eutectic solvent made from choline chloride and malonic acid (ChCl:MA). Reaction conditions were mild; work-up was easy, and further purification was not necessary. Given the inexpensive, nontoxic, and recyclable nature of ChCl:MA, this protocol is environmental friendly.
- Rokade, Sunil M.,Bhate, Prakash M.
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- Preparation method of high-purity topiramate
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The invention discloses a preparation method of high-purity topiramate. Under the condition of dissolving the topiramate into an organic solvent, a proper concentration of alkali is added, so that the topiramate slat forms solid to be separated out in the solvent; the solid is dissolved into water, and is acidified into a weak acidic state; the solid is a topiramate coarse product; the topiramate coarse product is recrystallized to obtain the high-purity topiramate. The preparation method of the high-purity topiramate has the advantages that the purity reaches 99.90 percent or higher; under the condition that the product purity reaches 99.9 percent or higher, the yield of the product keeps unchanged; no additional excessive cost is added. The operation is convenient; the process is safe; the industrial production is easy.
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Paragraph 0009; 0037; 0043; 0044; 0048
(2017/08/29)
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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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- COMPOSITIONS AND METHODS FOR THE TREATMENT OF EPILEPSY AND NEUROLOGICAL DISEASES
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The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for the treatment of epilepsy and neurological diseases may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of convulsions, Lennox-Gastaut syndrome, migraine, bipolar disorder, post traumatic stress disorder.
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Paragraph 0111; 0112; 0113
(2015/05/05)
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- Synthesis and membranoprotective properties of new disulfides with monoterpene and carbohydrate fragments
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A cooxidation of carbohydrate and terpene thiols gives mixtures of disulfides containing 51 - 90% of the unsymmetric product. Membranoprotective and antioxidant properties of obtained unsymmetric and symmetric disulfides were evaluated based on their ability to inhibit the H2O2-induced hemolysis of erythrocytes, as well as the accumulation of secondary products of the peroxy oxidation of lipids and the oxidation of hemoglobin.
- Pestova,Izmestev,Shevchenko,Rubtsova,Kuchin
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p. 723 - 731
(2015/11/27)
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- Synthesis and oxidation of thioglicosides underlain by neomenthanethiol, D-glucose, and D-fructose
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Synthesis of sulfides proceeding from neomenthanethiol, 1,2-O-isopropylidene-α-D-glucofuranose and 2,3:4,5-di-O-isopropylidene- β-D-fructopyranose was performed to get 65 and 54% yield respectively. Oxidation of the sulfides afforded diastereomeric sulfoxides in the yields from 40 to 53%, and diastereomeric excess (de) up to 36%. After removing the isopropylidene protection from 1-deoxy-1-[(1S,2S,5R)-2-isopropyl-5- methylcyclohexylsulfanyl]-2,3:4,5-di-O-isopropylidene-β-D-fructopyranose a water-soluble sulfide was obtained.
- Pestova,Izmest'Ev,Rubtsova,Kuchin
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p. 670 - 677
(2014/07/08)
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- An epoxidation approach to a chiral lactone: Application of the Shi epoxidation
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The large-scale epoxidation of the alkene 7 with the organo-catalyst, Epoxone (10), and Oxone as the oxidant is described. This is the first large-scale application of the Shi epoxidation methodology. The large-scale preparation of the catalyst 10 is also described. The potassium salt of the unsaturated acid precursor 7 was prepared by a Suzuki coupling from 3-fluorobenzyl chloride and the vinylborane 8 derived from 4-pentynoic acid.
- Ager, David J.,Anderson, Ken,Oblinger, Eric,Shi, Yian,Vanderroest, James
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- Triphenylphosphine polymer-bound/iodine complex: A suitable reagent for the preparation of O-isopropylidene sugar derivatives
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O-Isopropylidene derivatives of sugars are readily prepared by using the Lewis acid and dehydrating agent triphenylphosphine polymer-bound/I2 complex. This new method is characterized by smooth, non-equilibrating reaction conditions and a very clean, simple work-up, making it particularly suitable for O-isopropylidenation of sugars under mild conditions and with low environmental impact. Georg Thieme Verlag Stuttgart.
- Pedatella, Silvana,Guaragna, Annalisa,D'Alonzo, Daniele,De Nisco, Mauro,Palumbo, Giovanni
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p. 305 - 308
(2007/10/03)
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- 1,5 AND 1,4-ANHYDROKETOSES, METHODS FOR THE PREPARATION OF 1,5-AND 1,4-ANHYDROKETOSES, INTERMEDIATES, AND USES OF 1,5-AND 1,4-ANHYDROKETOSES
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The present invention relates to 1,4- and 1,5-anhydro-D-ketoses (monosaccharides, oligosaccharides and various glycoconjugates), e.g. 1,5-anhydro-D-fructose. Moreover, the invention provides synthetic methods and novel intermediates and precursors suitable for their preparation. The methods include catalytic- and/or pyrolitic sulfenic acid elimination of corresponding ?-hydroxy sulfoxides, N-deprotection of N-substituted-aminoglycals, O-deprotection of carbohydrate enolethers and/or O-acyl-substituted carbohydrate enols, and regio- and stereoselective modification and subsequent chemical transformation of bicyclic and/or tricyclic 1,4- and 1,5-anhydro-glycoderivatives. Furthermore, the present invention provides novel applications of 1,4- and 1,5-anhydroketoses within pharmaceutical, food and cosmetic industries.
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Page/Page column 73
(2008/06/13)
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- Process for the preparation of sulfamate derivatives
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An improved process for the preparation of sulfamate derivatives such as topiramate is provided comprising (a) reacting an alcohol with sulfuryl chloride in the presence of an amine base and in a first halogenated hydrocarbon solvent selected from the group consisting of aliphatic halogenated hydrocarbon solvents having 1 to 12 carbon atoms and at least three halogen atoms, aliphatic halogenated hydrocarbon solvents having 2 to 12 carbon atoms and less than three halogen atoms, aromatic halogenated hydrocarbon solvents having 6 to 18 carbon atoms and mixtures thereof to produce a chlorosulfate intermediate and (b) reacting the chlorosulfate intermediate with an amine of the formula R1NH2, wherein R1 is hydrogen or an alkyl from 1 to 4 carbon atoms, in a second halogenated hydrocarbon solvent selected from the group consisting of aliphatic halogenated hydrocarbon solvents having 1 to 12 carbon atoms and at least three halogen atoms, aliphatic halogenated hydrocarbon solvents having 2 to 12 carbon atoms and less than three halogen atoms, aromatic halogenated hydrocarbon solvents having 6 to 18 carbon atoms and mixtures thereof.
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Page/Page column 4-6
(2008/06/13)
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- Immunological consequences of methamphetamine protein glycation
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The drug of abuse methamphetamine has been found to participate in the aberrant glycation of proteins. The importance of this chemical process has been shown wherein mouse albumin was readily modified with methamphetamine, and injection of this protein into mice yields a significant immune response, even in the absence of adjuvants. Competition experiments revealed that although methamphetamine binds weakly to the elicited antibodies, the primary epitope is composed of both the methamphetamine moiety and glucose-derived cross-linking region. Implications of this phenonomenon in the context of drug addiction are discussed. Copyright
- Dickerson, Tobin J.,Yamamoto, Noboru,Ruiz, Diana I.,Janda, Kim D.
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p. 11446 - 11447
(2007/10/03)
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- Inhibition of the D-fructose transporter protein GLUT5 by fused-ring glyco-1,3-oxazolidin-2-thiones and -oxazolidin-2-ones
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The glucose transporter 5 (GLUT5) - a specific D-fructose transporter - belongs to a family of facilitating sugar transporters recently enlarged by the human genome sequencing. Prompted by the need to develop specific photolabels of these isoforms, we have studied the interaction of conformationally locked D-fructose and L-sorbose derived 1,3-oxazolidin-2-thiones and 1,3-oxazolidin-2-ones to provide a rational basis for an interaction model. The inhibition properties of the D-fructose transporter GLUT5 by glyco-1,3-oxazolidin-2-thiones and glyco-1,3-oxazolidin-2-ones is now reported. In vitro, the fused-rings systems tested showed an efficient inhibition of GLUT5, thus bringing new insights on the interaction of D-fructose with GLUT5.
- Girniene, Jolanta,Tatibouet, Arnaud,Sackus, Algirdas,Yang, Jing,Holman, Geoffrey D.,Rollin, Patrick
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p. 711 - 719
(2007/10/03)
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- Hydrogen isotopic profile in the characterization of sugars. Influence of the metabolic pathway
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The site-specific natural hydrogen isotope ratios of plant metabolites determined by 2H nuclear magnetic resonance (SNIF-NMR method) can provide powerful criteria for inferring mechanistic and environmental effects on biosynthetic pathways. This work examines the potential of isotopic profiles for the main constituents of carbohydrates, glucose and fructose, to distinguish different photosynthetic pathways. An appropriate analytical strategy, involving three suitable isotopic probes, has been elaborated with a view to measuring simultaneously, in conditions devoid of isotopic perturbations, all (or nearly all) of the carbon-bound hydrogen isotope ratios. It is shown that the type of photosynthetic metabolism, either C3 (sugar beet, orange, and grape), C4 (maize and sugar cane), or CAM (pineapple), and the physiological status of the precursor plant exert strong influences on the deuterium distribution in the sugar molecules. Consequently, this isotopic fingerprint may be a rich source of information for the comparison of mechanisms in metabolic pathways. In addition, it can provide complementary criteria to ethanol as a probe for the origin of sugars.
- Zhang, Ben-li,Billault, Isabelle,Li, Xiaobao,Mabon, Francoise,Remaud, Gerald,Martin, Maryvonne L.
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p. 1574 - 1580
(2007/10/03)
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- Stereochemistry of addition of carbanion reagents to 'diacetone fructose aldehyde'. Configurational assignment of a 1-deoxyheptulose derivative by X- ray crystallography and NMR studies directed to the assignment of isomeric adducts
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The addition of carbanionic reagents to 'diacetone fructose aldehyde' (6) was investigated with a focus on the stereocontrol. The Grignard reagents, MeMgBr, EtMgBr, i-PrMgBr, and MeMgI, gave a high bias (≥90%) for one diastereomer, assigned as the R-isomer, in ether at -78 to 0°C. The reaction of PhMgBr showed diminished diastereoselectivity under these conditions, with a significant dependence of the isomer ratio on temperature and solvent. PhCH2MgBr only afforded the adduct of 'allylic rearrangement', namely 13, with poor diastereocontrol (ca. 60:40). MeLi, t-BuLi, PhLi, and LiCH2CO2-t-Bu provided adducts of 6 enriched in the R-isomer in the range of 80-89%, whereas 2-lithio-2-ethyl-1,3-dithiane gave a 94:6 ratio of R:S adducts (15a:15b). The R absolute stereochemistry at the carbinol C1 center of 4a was established through X-ray analysis of sulfamate derivative 2a. Carbon-13 NMR chemical shift criteria (the chemical shifts for C1 and C3) were identified to facilitate the stereochemical assignment of C1 adducts of 6.
- Costanzo, Michael J.,Jaroskova, Libuse,Gauthier, Diane A.,Maryanoff, Bruce E.
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p. 689 - 703
(2007/10/03)
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- The synthesis of pure Amadori rearrangement products
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The term "Maillard reaction" is used to describe a complex set of reactions in foods leading to flavour generation and non-enzymatic browning.The first step in this process is the so-called Amadori rearrangement: a reducing saccharide and a peptide fragment react to form an Amadori Rearrangement Product (ARP).To be able to do model studies on flavour generation, gram amounts of pure ARP are required.In the present study, glucose-derived ARPs were synthesised from specifically protected and activated starting compounds.After deprotection and purification, pure ARPs were obtained.This is the first time that ARPs of dipeptides have been isolated.
- Noomen, S. N.,Breel, G. J.,Winkel, C.
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p. 321 - 324
(2007/10/02)
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- Acetalation studies. Part IX. Reaction of sucrose and some related sugars with acetone in the presence of iodine; a novel cleavage-isopropylidenation method
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An efficient cleavage-isopropylidenation reaction of sucrose, catalyzed by iodine, is described.Related D-fructofuranosyl-containing oligosaccharides and their individual monosaccharide units were treated in a similar manner to yield isopropylidenated monosaccharide derivatives.The reaction conditions are particularly mild and selective.Some mechanistic aspects of the procedure are also discussed.
- Verhart, Cor G. J.,Caris, Brigitte M. G.,Zwanenburg, Binne,Chittenden, Gordon J. F.
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p. 348 - 352
(2007/10/02)
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- Synthesis of aromatic Amadori compounds
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A series of O-isopropylidene protected aromatic Amadori compounds [N-(1-deoxy-D-fructos-1-yl)-L-amino acid esters] were synthesized by reacting 2,3:4,5-di-O-isopropylidene-1-O-(trifluoromethanesulfonyl)-D-fructopyra nose with alkyl esters of L-phenylalanine, L-tyrosine, and L-tryptophan. The Amadori compounds were obtained in much higher yields than those previously reported due to utilizing triflate as an extremely reactive leaving group at C-1 of the sugar reagent. The triflate derivative was prepared in high yield using the sterically hindered, non-nucleophilic base, 2,6-di-tert-butyl-4-methylpyridine, as proton acceptor. The Amadori compounds were characterized by 1H- or 13C-n.m.r. spectroscopy, as well as by i.r. and mass spectroscopy. 13C-n.m.r. spectroscopy was used to study the equilibria among the various ring forms of the free-hydroxy D-fructose-tryptophan compound.
- Lopez,Gruenwedel
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- Synthesis of Polymerizable Hexose Derivatives
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Polymerizable esters of methacrylic and acrylic acid with di-O-isopropylidenehexoses as alcohol components have been synthesized.
- Kossmehl, Gerhard,Volkheimer, Juergen
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p. 1127 - 1130
(2007/10/02)
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- SYNTHESIS OF Β-LACTAMS FROM SUGAR VINYL ETHERS AND ISOCYANATES
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Cycloaddition of tosyl isocyanate to sugar vinyl ethers followed by N-deprotection affords β-lactams with fairly good asymmetric induction.
- Kaluza, Zbigniew,Fudong, Wang,Belzecki, Czeslaw,Chmielewski, Marek
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p. 5171 - 5172
(2007/10/02)
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- GAS CHROMATOGRAPHY-MASS SPECTROMETRY OF HEXULOSES AND PENTULOSES AS THEIR O-ISOPROPYLIDENE DERIVATIVES: ANALYSIS OF PRODUCT MIXTURES FROM TRIOSE ALDOL-CONDENSATIONS
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Identification and quantitation of hexuloses and pentuloses in mixtures has been achived by gas chromatography-mass spectrometry of their O-isopropylidene derivatives.The method has been applied to product mixtures from triose aldol-condensations.The use of strongly basic anion-exchange resins as catalysts in the aldol condensation gives considerably higher proportions of fructose than when alkali or alkaline-earth hydroxides are applied.
- Morgenlie, Svein
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p. 215 - 222
(2007/10/02)
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- NOUVELLE METHODE DE SYNTHESE STEREOSELECTIVE DE GLYCOSIDES. SYNTHESE DES α,α-TREHALOSE, ANALOGUES galacto, manno ET AUTRES α-D-GLYCOSIDES
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In the presence of trifluoromethanesulfonic (triflic) anhydride as catalyst and dichloromethane as solvent, in the cold, 2,3,4,6-tetra-O-benzyl-D-glucopyranose, 2,3,4,6-tetra-O-benzyl-D-galactopyranose, and 2,3,4,6-tetra-O-benzyl-D-mannopyranose were converted in almost quantitative yield to a 2:1 mixture of the corresponding α,α-(1->1) and α,β-(1->1) disaccharides.Hence, pure 2,3,4,6,2',3',4',6'-octa-O-benzyl derivatives of α,α-trehalose, and the D-galacto and D-manno analogues were obtained, after column chromatography, in 55-65 percent yield.Hydrogenolysis gave the corresponding free sugars.The pure anomers were obtained in 10-34 percent yield.The potentiality of the method was demonstrated by the synthesis of 2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl 2,3:4,5-di-O-isopropylidene-β-D-fructopyranoside in 50 percent yield, and of N-(benzyloxycarbonyl)-3-O-(2,3,4,6-tetra-O-benzyl-α-D-glucopyranosyl)-L-threonine methyl ester in 65 percent yield.
- Pavia, Andre A.,Rocheville, Jean-Michel,Ung, Sak N.
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- β-(Trimethylsilyl)ethoxymethyl chloride. A new reagent for the protection of the hydroxyl group
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Reactions of β-(trimethylsilyl)ethoxymethyl chloride with alcohols afford the corresponding ethers in high yield. Deprotection using n-Bu4NF in THF or HMPA cleanly regenerates the hydroxyl function.
- Lipshutz, Bruce H.,Pegram, Joseph J.
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p. 3343 - 3346
(2007/10/02)
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