- Discovery of Salidroside-Derivated Glycoside Analogues as Novel Angiogenesis Agents to Treat Diabetic Hind Limb Ischemia
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Therapeutic angiogenesis is a potential therapeutic strategy for hind limb ischemia (HLI); however, currently, there are no small-molecule drugs capable of inducing it at the clinical level. Activating the hypoxia-inducible factor-1 (HIF-1) pathway in skeletal muscle induces the secretion of angiogenic factors and thus is an attractive therapeutic angiogenesis strategy. Using salidroside, a natural glycosidic compound as a lead, we performed a structure-activity relationship (SAR) study for developing a more effective and druggable angiogenesis agent. We found a novel glycoside scaffold compound (C-30) with better efficacy than salidroside in enhancing the accumulation of the HIF-1α protein and stimulating the paracrine functions of skeletal muscle cells. This in turn significantly increased the angiogenic potential of vascular endothelial and smooth muscle cells and, subsequently, induced the formation of mature, functional blood vessels in diabetic and nondiabetic HLI mice. Together, this study offers a novel, promising small-molecule-based therapeutic strategy for treating HLI.
- Han, Jingxuan,He, Yun,Huang, Song,Kasim, Vivi,Liu, Caiping,Marcelina, Olivia,Miyagishi, Makoto,Nugrahaningrum, Dyah Ari,Wang, Guixue,Wu, Shourong,Zou, Meijuan
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- 2-: O-Benzyloxycarbonyl protected glycosyl donors: A revival of carbonate-mediated anchimeric assistance for diastereoselective glycosylation
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By reviving an old idea, we demonstrate that alkoxycarbonyl groups can be used in glycosylation reactions to achieve full stereocontrol through participation of a carbonate moiety at O-2. Various benzyloxycarbonyl-protected glycosyl donors were prepared and used for efficient 1,2-trans glycosylation of base-labile compounds and the synthesis of glycosyl esters.
- Weber, Julia,Svatunek, Dennis,Krauter, Simon,Tegl, Gregor,Hametner, Christian,Kosma, Paul,Mikula, Hannes
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supporting information
p. 12543 - 12546
(2019/10/28)
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- A Sustainable One-Pot, Two-Enzyme Synthesis of Naturally Occurring Arylalkyl Glucosides
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A sustainable, convenient, scalable, one-pot, two-enzyme method for the glucosylation of arylalkyl alcohols was developed. The reaction scheme is based on a transrutinosylation catalyzed by a rutinosidase from A. niger using the cheap commercially available natural flavonoid rutin as glycosyl donor, followed by selective “trimming” of the rutinoside unit catalyzed by a rhamnosidase from A. terreus. The process was validated with the syntheses of several natural bioactive glucosides, which could be isolated in up to 75 % yield without silica-gel chromatography.
- Bassanini, Ivan,Krejzová, Jana,Panzeri, Walter,Monti, Daniela,K?en, Vladimir,Riva, Sergio
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p. 2040 - 2045
(2017/05/16)
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- Chemoenzymatic synthesis of β-D-glucosides using cellobiose phosphorylase from Clostridium thermocellum
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Abstract Over the past decade, disaccharide phosphorylases have been successfully applied for the synthesis of numerous α-glucosides. In contrast, much less research has been done with respect to the production of β-glucosides. Although cellobiose phosphorylase was already successfully used for the synthesis of various disaccharides and branched trisaccharides, its glycosylation potential towards small organic compounds has not been explored to date. Unfortunately, disaccharide phosphorylases typically have a very low affinity for non-carbohydrate acceptors, which urges the addition of solvents. The ionic liquid AMMOENGTM 101 and ethyl acetate were identified as the most promising solvents, allowing the synthesis of various β-glucosides. Next to hexyl, heptyl, octyl, nonyl, decyl and undecyl β-D-glucopyranosides, also the formation of vanillyl 4-O-β-D-glucopyranoside, 2-phenylethyl β-D-glucopyranoside, β-citronellyl β-D-glucopyranoside and 1-O-β-D-glucopyranosyl hydroquinone was confirmed by nuclear magnetic resonance spectroscopy and mass spectrometry. Moreover, the stability of cellobiose phosphorylase could be drastically improved by creating cross-linked enzyme aggregates, while the efficiency of the biocatalyst for the synthesis of octyl β-D-glucopyranoside was doubled by imprinting with octanol. The usefulness of the latter system was illustrated by performing three consecutive batch conversions with octanol imprinted cross-linked enzyme aggregates, yielding roughly 2 g of octyl β-D-glucopyranoside.
- De Winter, Karel,Van Renterghem, Lisa,Wuyts, Kathleen,Pelantová, Helena,K?en, Vladimír,Soetaert, Wim,Desmet, Tom
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p. 1961 - 1969
(2015/06/02)
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- Short synthesis of the common trisaccharide core of kankanose and kankanoside isolated from Cistanche tubulosa
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A short synthetic approach was developed for the synthesis of a common trisaccharide core found in kankanose, kankanoside F, H1, H 2, and I isolated from the medicinally active plant Cistanche tubulosa. All glycosylations were carried out under nonmetallic reaction conditions. Yields were very good in all intermediate steps.
- Guchhait, Goutam,Misra, Anup Kumar
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p. 705 - 709
(2013/06/05)
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- Using ionic liquid cosolvents to improve enzymatic synthesis of arylalkyl β-d-glucopyranosides
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Enzymatic synthesis of various arylalkyl β-d-glucopyranosides catalyzed by prune (Prunus domestica) seed meal via reverse hydrolysis in the mixture of organic solvent, ionic liquid (IL) and phosphate buffer was described. Among four hydrophilic organic solvents tested, ethylene glycol diacetate (EGDA) was found to be the most suitable for enzymatic synthesis of salidroside, a bioactive compound of commercial interest, from d-glucose and tyrosol. The effects of the nature of ionic liquids and their contents on the enzymatic glucosylation were studied. The addition of a suitable amount of ILs including denaturing ones was favorable to shift the reaction equilibrium toward the synthesis, thus improving the yields. Among the examined ILs, the novel IL [BMIm]I proved to be the best. And this IL was applied as the solvent in biocatalysis for the first time. The yields were found to be enhanced between 0.2-fold and 0.5-fold after the addition of 10% (v/v) [BMIm]I. In 10% (v/v) [BMIm]I-containing system, the desired arylalkyl β-d-glucopyranosides were synthesized with 15-28% yields, among which salidroside was obtained with a yield of 22%. .
- Yang, Rong-Ling,Li, Ning,Zong, Min-Hua
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experimental part
p. 24 - 28
(2012/05/19)
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- Synthesis, biological activity of salidroside and its analogues
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Salidroside is a phenylpropanoid glycoside isolated from Rhodiola rosea L., a traditional Chinese medicinal plant, and has displayed a broad spectrum of pharmacological properties. In this paper, about 18 novel salidroside analogues were prepared through Koenigs-Knorr method, the effects of these compounds over PC12 was assessed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The novel compounds differ in the substituents attached to the benzene ring or in the glycosyl donor. According to the data, compounds (3,5-dimethoxyphenyl)methyl β-D-glucopyranoside and (3,5-dimethoxyphenyl) methyl β-D-galactopyranoside with methoxy group at 3 and 5-positions of the benzene ring were the most viability at concentration of 300 μmol/l and 60 μmol/l, respectively.
- Guo, Yibing,Zhao, Yahong,Zheng, Cheng,Meng, Ying,Yang, Yumin
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experimental part
p. 1627 - 1629
(2011/02/24)
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- A convenient stereoselective synthesis of β-D-glucopyranosides
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The Koenigs-Knorr method plays a prominent role in the stereoselective synthesis of alkyl D-glucopyranosides via glycosidic linkage. Such an approach requires costly and toxic promoter salts of silver or mercury, which have additional separation problems. In a novel method a less toxic promoter salt like LiCO3 is used for glycosidation of several fatty alcohols including an aromatic alcohol. LiCO3 can be easily separated from the reaction mass and gives good yield.
- Joshi, Vishal Y.,Sawant, Manohar R.
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p. 461 - 465
(2007/10/03)
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- Chemoenzymatic synthesis of naturally occurring phenethyl (1→6)-β-D-gluco-pyranosides
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Direct β-glucosidation between phenethyl alcohol and D-glucose (5) using the immobilized β-glucosidase from almonds with the synthetic prepolymer ENTP-4000 gave a phenethyl β-D-glucoside (1) in 34% yield. The coupling of the phenethyl O-β-D-glucopyranoside congener (8) and methylthio-2,3,4-tri-O-acetyl-β-D-xylopyranoside (9), 2,3,4-tri-O-acetyl- α-L-arabinopyranosyl bromide (11), and methylthio 2,3,4-tri-O-acetyl- α-L-rhamnopyranoside (13) afforded the coupled products (10, 12, and 14), respectively. Deprotection of the coupled products (10, 12, and 14) afforded the synthetic phenethyl O-β-D-xylopyranosy-(1→6)- β-D- glucopyranoside (2), phenethyl O-α-L-arabinopyranosy-(1→6)-β-D- glucopyranoside (3), and phenethyl O-α-L-rhamnopyranosy- (1→6)-β-D-glucopyranoside (4), respectively.
- Kawahara, Eiji,Nishiuchi, Miho,Fujii, Mikio,Kato, Keisuke,Ida, Yoshiteru,Akita, Hiroyuki
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p. 1461 - 1470
(2007/10/03)
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- Simple synthesis of β-D-glycopyranosides using β-glycosidase from almonds
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Enzymatic glycosidation of twenty-one kinds of alcohols (n-hepanol, n-octanol, 2-phenylethanol, 3-phenylpropanol, 4-phenylbutanol, 5-phenylpentanol, 6-phenylhexanol, furfury alcohol, 2-pyridinemethanol, isobutanol, isopentanol, p-methoxycinnamylalcohol) including secondary alcohols (isopropanol, cyclohexanol, 1-phenylethanol) and 1, ω-alkanediols (1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol), salicyl alcohol and 4-nitrophenyl β-D-glucopyranoside (5) using β-glucosidase from almonds stereoselectively gave the corresponding β-D-glucopyranosides in moderate yield.
- Kurashima, Katsumi,Fujii, Mikio,Ida, Yoshiteru,Akita, Hiroyuki
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p. 270 - 275
(2007/10/03)
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- Substrate specificity of beta-primeverosidase, a key enzyme in aroma formation during oolong tea and black tea manufacturing.
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We synthesized nine kinds of diglycosides and a monoglycoside of 2-phenylethanol to investigate the substrate specificity of the purified beta-primeverosidase from fresh leaves of a tea cultivar (Camellia sinensis var. sinensis cv. Yabukita) in comparison with the apparent substrate specificity of the crude enzyme extract from tea leaves. The crude enzyme extract mainly showed beta-primeverosidase activity, although monoglycosidases activity was present to some extent. The purified beta-primeverosidase showed very narrow substrate specificity with respect to the glycon moiety, and especially prominent specificity for the beta-primeverosyl (6-O-beta-D-xylopyranosyl-beta-D-glucopyranosyl) moiety. The enzymes hydrolyzed naturally occurring diglycosides such as beta-primeveroside, beta-vicianoside, beta-acuminoside, beta-gentiobioside and 6-O-alpha-L-arabinofuranosyl-beta-D-glucopyranoside, but were unable to hydrolyze synthetic unnatural diglycosides. The purified enzyme was inactive toward 2-phenylethyl beta-D-glucopyranoside. The enzyme hydrolyzed each of the diglycosides into the corresponding disaccharide and 2-phenylethanol. These results indicate the beta-primeverosidase, a diglycosidase, to be a key enzyme involved in aroma formation during the tea manufacturing process.
- Ma,Mizutani,Hiratake,Hayashi,Yagi,Watanabe,Sakata
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p. 2719 - 2729
(2007/10/03)
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- Sensitive and Selective Screening for 6′-O-Malonylated Glucoconjugates in Plants
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Using synthesized reference compounds a screening for benzyl, 2-phenylethyl, geranyl, citronellyl, and 2,5-dimethyl-4-hydroxy-3(2H)-furanone 6′-O-malonyl β-D-glucopyranosides in various plant tissues was performed by high-performance liquid chromatography - electrospray ionization - tandem mass spectrometry (HPLC-ESI-MS/MS). The results obtained with fruits (guava; raspberry; strawberry), leaves (green tea; vine), and mountain papaya (Carica pubescens) peel indicate that malonylation of glycoconjugates is a common pathway in plant secondary metabolism.
- Withopf, Barbara,Richling, Elke,Roscher, René,Schwab, Wilfried,Schreier, Peter
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p. 907 - 911
(2007/10/03)
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- Synthesis of 2-Phenylethyl α-Glucoside
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2-Phenylethyl α-glucoside was synthesized from 2-phenylethanol and α-D-glucose in the presence of p-toluenesulfonic acid monohydrate at 75 deg C and was isolated by continuous extraction, during which hexane was used to remove the excess 2-phenylethanol and then ethyl acetate was used to isolate the product.The spectral data including IR, 1H NMR, 13C NMR, and MS of this compound are presented. Keywords: 2-Phenylethanol; 2-phenylethyl α-glucoside; α-D-glucose; p-toluenesulfonic acid
- Shu, Chi-Kuen,Lawrence, Brian M.
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p. 1732 - 1733
(2007/10/02)
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- Enzyme-catalysed synthesis of alkyl β-D-Glucosides in organic media
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The synthetic potential of Almond β-D-Glucosidase for the synthesis of alkyl glucosides was studied. The regio and stereoselectivity of the synthesis were analysed for the reverse hydrolysis and the transglucosylation methods in tert-butanol and acetonitrile media.
- Vic, Gabin,Thomas, Daniel
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p. 4567 - 4570
(2007/10/02)
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- Preparation of New Terpenyl β-D-Glucopyranosides by a Modified Koenigs-Knorr Procedure.
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Ten new hemi- and monoterpenyl β-D-glucopyranosides have been prepared by a modification of the Koenigs-Knorr procedure which utilises silver fluoroacetate as a soluble catalyst coupled with the introduction of a basic ion-exchange resin to effect the deacetylation step.Most of these compounds could not be obtained in acceptable yields using the classical procedure.
- Ackermann, Irmtraud E.,Banthorpe, Derek V.,Fordham, William D.,Kinder, John P.,Poots, Ian
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- Biotransformation of phenylcarboxylic acids by plant cell cultures
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A suspension culture of Glycyrrhiza echinata converted benzoic acid into its glucosyl ester. Suspension cultures of Aconitum japonicum, Coffea arabica, Dioscoreophyllum cumminsii and Nicotiana tabacum, transformed benzoic acid into its gentiobiosyl ester in addition to the glucosyl ester. The suspension cultures of A.japonicum and G. echinata converted phenylacetic acid into the esters attached to the C-6 position of glucose, that is, 6-O-phenylacetyl-d-glucose and ethyl 6-O-phenylacetyl-β-d-glucopyranoside. That of D. cumminsii converted phenylacetic acid into the glucose ester and also into phenethyl β-d-glucopyranoside showing glucosylation after the reduction of the carboxylic group. These suspension cultures converted cinnamic acid into p-coumaric acid and its glucosyl ester and p-coumaric acid into its glucosyl ester. However, the conversion of caffeic acid was not observed. The suspension cultures of A.japonicum and C. arabica converted 3-phenylpropionic acid into its gentiobiosyl ester. On the other hand, the culture of D. cumminsii did not produce the glycosyl ester but instead 3-(4-hydroxyphenyl)propionic acid was formed, thus showing hydroxylation capability.
- Ushiyama, Masashi,Kumagai, Shigehiro,Furuya, Tsutomu
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p. 3335 - 3339
(2007/10/02)
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- Aryl β-d-glucosides from Carica papaya fruit
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Benzyl β-d-glucoside, 2-phenylethyl β-d-glucoside, 4-hydroxyphenyl-2-ethyl β-d-glucoside and four isomeric malonated benzyl β-d.
- Schwab, Wilfried,Schreier, Peter
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p. 1813 - 1816
(2007/10/02)
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- Synthesis of β-Alkyl Glucosides by Enzymic Transglucosylation
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Lactase from Kluyveromyces lactis was found to have high transglucosylation activity, transferring the glucosyl group of aryl glucoside to an alcoholic hydroxyl group in high yield.Both primary and secondary alcohols can accept the glucosyl group.Transglucosylation to glycol yielded a single kind of glucoside.A very hydrophilic alcohol, such as glycerol, could not serve as a substrate in this system.Hydrophobic alcohols slightly soluble in water were glucosylated in a two-phase system consisting of water and an organic solvent immiscible with water.Keywords - transglucosylation; transglycosylation; β-glucoside; lactase; Kluyveromyce s lactis; phenyl β-D-glucopyranoside; hydrophobic alcohol; two-phase system; alkyl glucoside; enzymic transglucosylation
- Mitsuo, Naoki,Takeichi, Hiroshi,Satoh, Toshio
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p. 1183 - 1187
(2007/10/02)
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