- Halide-mediated regioselective 6-O-glycosylation of unprotected hexopyranosides with perbenzylated glycosyl bromide donors
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The regio- and stereoselective glycosylation at the 6-position in 2,3,4,6-unprotected hexopyranosides has been investigated with dibutyltin oxide as the directing agent. Perbenzylated hexopyranosyl bromides were employed as the donors and the glycosylations were promoted by tetrabutylammonium bromide. The couplings were completely selective for both glucose and galactose donors and acceptors as long as the stannylene acetal of the acceptor was soluble in dichloromethane. This gave rise to a number of 1,2-cis-linked disaccharides in reasonable yields. Mannose donors and acceptors, on the other hand, did not react in the glycosylation under these conditions.
- Niedbal, Dominika Alina,Madsen, Robert
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Read Online
- 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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- Indolylthio glycosides as effective building blocks for chemical glycosylation
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The S-indolyl (SIn) anomeric moiety was investigated as a new leaving group that can be activated for chemical glycosylation under a variety of conditions including thiophilic and metal-assisted pathways. Understanding of the reaction pathways for the SIn moiety activation was achieved via the extended mechanistic study. Also reported is how the new SIn donors fit into selective activation strategies for oligosaccharide synthesis.
- Demchenko, Alexei V.,Shrestha, Ganesh,Panza, Matteo,Singh, Yashapal,Rath, Nigam P.
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p. 15885 - 15894
(2021/01/19)
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- Synthesis of Glycosyl Chlorides and Bromides by Chelation Assisted Activation of Picolinic Esters under Mild Neutral Conditions
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A general method has been developed for the formation of glycosyl chlorides and bromides from picolinic esters under mild and neutral conditions. Benchtop stable picolinic esters are activated by a copper(II) halide species to afford the corresponding products in high yields with a traceless leaving group. Rare β glycosyl chlorides are accessible via this route through neighboring group participation. Additionally, glycosyl chlorides with labile protecting groups previously not easily accessible can be prepared.
- Balzer, Paul G.,Blaszczyk, Stephanie A.,Duan, Xiyan,Ma, Zhi-Xiong,Simmons, Christopher J.,Stevens, Christopher M.,Tang, Weiping,Wang, Hao-Yuan,Wen, Peng,Ye, Wenjing,Yin, Dan
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supporting information
(2020/02/28)
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- Koenigs–Knorr Glycosylation Reaction Catalyzed by Trimethylsilyl Trifluoromethanesulfonate
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The discovery that traditional silver(I)-oxide-promoted glycosidations of glycosyl bromides (Koenigs–Knorr reaction) can be greatly accelerated in the presence of catalytic trimethylsilyl trifluoromethanesulfonate (TMSOTf) is reported. The reaction conditions are very mild that allowed for maintaining a practically neutral pH and, at the same time, providing high rates and excellent glycosylation yields. In addition, unusual reactivity trends among a series of differentially protected glycosyl bromides were documented. In particular, benzoylated α-bromides were much more reactive than their benzylated counterparts under these conditions.
- Singh, Yashapal,Demchenko, Alexei V.
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supporting information
p. 1461 - 1465
(2019/01/04)
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- β-Selective C-Glycosylation and its Application in the Synthesis of Scleropentaside A
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C-Glycosides are carbohydrates that bear a C?C bond to an aglycon at the anomeric center. Due to their high stability towards chemical and enzymatic hydrolysis, these compounds are widely used as carbohydrate mimics in drug development. Herein, we report a general and exclusively β-selective method for the synthesis of a naturally abundant acyl-C-glycosidic structural motif first found in the scleropentaside natural product family. A Corey–Seebach umpolung reaction as the key step in the synthesis of scleropentaside A and analogues enables the β-selective construction of the anomeric C?C bond starting from unprotected carbohydrates in only four steps. The one-pot approach is highly atom-efficient and avoids the use of toxic heavy metals.
- Boehlich, G. Jacob,Schützenmeister, Nina
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supporting information
p. 5110 - 5113
(2019/03/17)
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- β-Selective One-Pot Synthesis of Acyl-C-Glycosides via Corey-Seebach Umpolung Reaction
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C-Glycosides are commonly used as carbohydrate mimics in drug development due to their stability against enzymatic and chemical hydrolysis. In this Synpacts article we elaborate on our fast and efficient β-selective approach towards protected and unprotected acyl glycosides. Application of a Corey-Seebach umpolung reaction enables the exclusive formation of the β-Anomer of aromatic acyl-C-glycosides in good to excellent yields. 1 Introduction 2 C-Glycosylation of Benzylated Glycosyl Donors 3 C-Glycosylation of Silylated Glycosyl Donors 4 Conclusion.
- Boehlich, G. Jacob,Schützenmeister, Nina
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p. 1935 - 1939
(2019/10/22)
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- Establishment of Guidelines for the Control of Glycosylation Reactions and Intermediates by Quantitative Assessment of Reactivity
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Stereocontrolled chemical glycosylation remains a major challenge despite vast efforts reported over many decades and so far still mainly relies on trial and error. Now it is shown that the relative reactivity value (RRV) of thioglycosides is an indicator for revealing stereoselectivities according to four types of acceptors. Mechanistic studies show that the reaction is dominated by two distinct intermediates: glycosyl triflates and glycosyl halides from N-halosuccinimide (NXS)/TfOH. The formation of glycosyl halide is highly correlated with the production of α-glycoside. These findings enable glycosylation reactions to be foreseen by using RRVs as an α/β-selectivity indicator and guidelines and rules to be developed for stereocontrolled glycosylation.
- Chang, Chun-Wei,Wu, Chia-Hui,Lin, Mei-Huei,Liao, Pin-Hsuan,Chang, Chun-Chi,Chuang, Hsiao-Han,Lin, Su-Ching,Lam, Sarah,Verma, Ved Prakash,Hsu, Chao-Ping,Wang, Cheng-Chung
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supporting information
p. 16775 - 16779
(2019/11/03)
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- Regenerative Glycosylation
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Previously, we communicated 3,3-difluoroxindole (HOFox)-mediated glycosylations wherein 3,3-difluoro-3H-indol-2-yl (OFox) imidates were found to be key intermediates. Both the in situ synthesis from the corresponding glycosyl bromides and activation of the OFox imidates could be conducted in a regenerative fashion. Herein, we extend this study to the synthesis of various glycosidic linkages using different sugar series. The main outcome of this study relates to enhanced yields and/or reduced reaction times of glycosylations. The effect of HOFox-mediated reactions is particularly pronounced in case of unreactive glycosyl donors and/or glycosyl acceptors. A multistep regenerative synthesis of oligosaccharides is also reported.
- Singh, Yashapal,Wang, Tinghua,Geringer, Scott A.,Stine, Keith J.,Demchenko, Alexei V.
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p. 374 - 381
(2018/01/01)
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- Method for synthesizing ipragliflozin
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The invention discloses a method for synthesizing ipragliflozin. The method comprises the following steps: (1) generating alkylation reaction by formula-4 compound and formula-5 compound to generate aformula-6 compound; (2) carrying out deprotection on the formula-6 compound to generate a formula-7 compound, i.e., ipragliflozin. Compared with the prior art, the preparation method disclosed by theinvention is characterized in that adopted starting raw materials are cheap and can be easily obtained, a synthesis route is short, operation is convenient, cost is lower and general yield is high. The method conforms to the concept of green chemistry and is suitable for industrial production. (The formulas are shown in the description.).
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Paragraph 0041; 0044; 0045; 0060; 0075
(2018/07/30)
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- Pyranoside-into-Furanoside Rearrangement of 4-Pentenyl Glycosides in the Synthesis of a Tetrasaccharide-Related to Galactan I of Klebsiella pneumoniae
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An efficient strategy for synthesis of a spacer-armed tetrasaccharide related to galactan I of Klebsiella pneumoniae is described, which uses newly developed acid-free conditions for the pyranoside-into-furanoside (PIF) rearrangement of a digalactoside bearing a 4-pentenyl group at the anomeric position. The 4-pentenyl aglycon was successfully used both as a leaving group in the glycosylation of 3-(trifluoroacetamido)propanol, and as a temporary anomeric protecting group, allowing conversion into an imidate donor. Regioselective coupling of the disaccharide blocks gave the desired tetrasaccharide sequence required for investigation of the interaction of galactan I with immune-system proteins.
- Verkhnyatskaya, Stella A.,Krylov, Vadim B.,Nifantiev, Nikolay E.
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p. 710 - 718
(2017/02/05)
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- GLYCOMIMETIC INHIBITORS OF PA-IL AND PA-IIL LECTINS
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Compounds, compositions, and methods for the diagnosis and/or treaimeni of medical conditions involving infections with and colonization by Fseudomonas bacteria including, for example, Fseudomonas aeruginosa in the lungs of patients with cystic fibrosis are described.
- -
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Paragraph 0015; 0066
(2018/01/17)
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- Regenerative glycosylation under nucleophilic catalysis
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This article describes 3,3-difluoroxindole (HOFox)-mediated glycosylation. The uniqueness of this approach is that both the in situ synthesis of 3,3-difluoro-3H-indol-2-yl (OFox) glycosyl donors and activation thereof can be conducted in a regenerative fashion as is a typical reaction performed under nucleophilic catalysis. Only a catalytic amount of the OFox imidate donor and a Lewis acid activator are present in the reaction medium. The OFox imidate donor is constantly regenerated upon its consumption until glycosyl acceptor has reacted.
- Nigudkar, Swati S.,Stine, Keith J.,Demchenko, Alexei V.
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supporting information
p. 921 - 923
(2014/02/14)
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- Combined Lewis acid and Br?nsted acid-mediated reactivity of glycosyl trichloroacetimidate donors
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Biomimetic conditions for a synthetic glycosylation reaction, inspired by the highly conserved functionality of carbohydrate active enzymes, were explored. At the outset, we sought to generate proof of principle for this approach to developing catalytic systems for glycosylation. However, control reactions and subsequent kinetic studies showed that a stoichiometric, irreversible reaction of the catalyst and glycosyl donor was occurring, with a remarkable rate variance depending upon the structure of the carboxylic acid. It was subsequently found that a combination of Br?nsted acid (carboxylic acid) and Lewis acid (MgBr2) was unique in catalyzing the desired glycosylation reaction. Thus, it was concluded that the two acids act synergistically to catalyze the desired transformation. The role of the catalytic components was tested with a number of control reactions and based on these studies a mechanism is proposed herein.
- Gould, Nathan D.,Liana Allen,Nam, Brandon C.,Schepartz, Alanna,Miller, Scott J.
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- GLYCOSYLATED VALPROIC ACID ANALOGS AND USES THEREOF
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Glycosylated valproic acid and its analogs are provided. In some embodiments, the glycosylated valproic acid and its analogs have improved solubility and are ideal for drug delivery to treat a variety of diseases.
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- Glycosidation of thioglycosides in the presence of bromine: Mechanism, reactivity, and stereoselectivity
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Elaborating on previous studies by Lemieux for highly reactive "armed" bromides, we discovered that β-bromide of the superdisarmed (2-O-benzyl-3,4,6-tri-O-benzoyl) series can be directly obtained from the thioglycoside precursor. When this bromide is glycosidated, α-glycosides form exclusively; however, the yields of such transformations may be low due to the competing anomerization into α-bromide that is totally unreactive under the established reaction conditions.
- Kaeothip, Sophon,Yasomanee, Jagodige P.,Demchenko, Alexei V.
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scheme or table
p. 291 - 299
(2012/03/08)
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- Synthesis of glycosyl fluorides from thio-, seleno-, and telluroglycosides and glycosyl sulfoxides using aminodifluorosulfinium tetrafluoroborates
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Glycosyl fluorides can be synthesized from thio-, seleno-, and telluroglycosides and glycosyl sulfoxides using the aminodifluorosulfinium tetrafluoroborate reagents Xtalfluor-E and -M, with or without added N-bromosuccinimide. Mechanistic studies provide evidence that fluoride is delivered from the tetrafluoroborate counterion.
- Tsegay, Sammi,Williams, Rohan J.,Williams, Spencer J.
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scheme or table
p. 16 - 22
(2012/09/21)
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- New method for regioselective glycosylation employing saccharide oxyanions
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As an alternative concept for glycosylation, the prior activation of acceptor hydroxy groups for selective glycosidic bond formation, was investigated to give complex oligosaccharides. Oxyanions obtained from partially protected saccharides were glycosylated by employing glycopyranosyl halides, and the regiochemical results were studied. Initially, partially methylated methyl-α-D-glucopyranosides were used as a model system to study the underlying mechanistic principles of base-promoted glycosylation. High regioselectivities and stereospecific glycosidic bond formations were achieved, and the scope of the methodology was extended with different perbenzylated glycosyl donors.
- Matwiejuk, Martin,Thiem, Joachim
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experimental part
p. 5860 - 5878
(2011/11/06)
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- Silver(I) tetrafluoroborate as a potent promoter for chemical glycosylation
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We have identified silver tetrafluoroborate (AgBF4) as an excellent promoter for the activation of various glycosyl donors including glycosyl halides, trichloroacetimidates, and thioimidates. Easy handling and no requirement for azeotropic dehydration prior to application makes AgBF4 especially beneficial in comparison to the commonly used AgOTf. Selective activation of glycosyl halides or thioimidates over thioglycosides or n-pentenyl glycosides, including simple sequential one-pot syntheses, has also been demonstrated. Versatility of glycosyl thioimidates was further explored by converting these intermediates into a variety of other classes of glycosyl donors.
- Kaeothip, Sophon,Pornsuriyasak, Papapida,Demchenko, Alexei V.
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p. 1542 - 1545
(2008/09/19)
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- From disulfide- to thioether-linked glycoproteins
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(Chemical Presented) Strengthening the bond: The introduction of a thiol tag in combination with chemoselective ligation to form a disulfide-linked bioconjugate is a selective and useful method for site-selective protein glycosylation. The phosphine-mediated desulfurization of such glycoconjugates to their reductant-resistant thioether-linked counterparts completes a convergent, site-selective synthesis of thioether-linked glycoproteins (see scheme).
- Bernardes, Goncalo J. L.,Grayson, Elizabeth J.,Thompson, Sam,Chalker, Justin M.,Errey, James C.,El Oualid, Farid,Claridge, Timothy D. W.,Davis, Benjamin G.
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supporting information; experimental part
p. 2244 - 2247
(2009/02/07)
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- Glycomimetic inhibitors of the PA-IL lectin, PA-IIL lectin or both the lectins from pseudomonas
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Compositions and methods are provided related to Pseudomonas bacteria. The compositions and methods may be used for diagnosis and therapy of medical conditions involving infection with Pseudomonas bacteria. Such infections include Pseudomonas aeruginosa i
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Page/Page column 10
(2008/06/13)
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- High-Yield Syntheses of Tetra-O-benzyl-α-D-glucopyranosyl bromide and Tetra-O-pivaloyl-α-D-glucopyranosyl bromide and their Advantage in the Koenigs-Knorr Reaction
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Several improved approaches for the preparation of tetra-O-benzyl-α- D-glucopyranosyl bromide and tetra-O-pivaloyl-α-D-glucopyranosyl bromide are discussed. The importance of these compounds, which are useful glycosyl donors, was demonstrated by successful preparation of cholesteryl glucopyranosides in an almost neutral medium without the formation of orthoesters. In addition, accurate 1H and 13C NMR resonance assignments of the synthesized cholesteryl glycosides were performed by 2D NMR spectroscopy. Springer-Verlag 2006.
- Presser, Armin,Kunert, Olaf,Poetschger, Irmgard
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p. 365 - 374
(2007/10/03)
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- Glycosyl disulfides: Novel glycosylating reagents with flexible aglycon alteration
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Glycosyl disulfides have been shown for the first time to be effective glycosyl donors. Glucosylation and galactosylation of a panel of representative alcohol acceptors allowed the formation of 28 simple glycosides, disaccharides, and glycoamino acids in yields of up to 90%. As well as providing a novel class of effective glycosyl donors, the ability to easily alter the nature of the aglycon and the ability to differently activate donors that differ only in their aglycon simply through altering conditions lends glycosyl disulfide donors to their use in latent-active reactivity tuning strategies.
- Grayson, Elizabeth J.,Ward, Sarah J.,Hall, Alison L.,Rendle, Phillip M.,Gamblin, David P.,Batsanov, Andrei S.,Davis, Benjamin G.
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p. 9740 - 9754
(2007/10/03)
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- REAGENTS AND METHODS FOR THE FORMATION OF DISULFIDE BONDS AND THE GLYCOSYLATION OF PROTEINS
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Methods and reagents for the formation of disulfide bonds, particularly in proteins, peptides and amino acids. The methods and reagents are particularly useful for the controlled glycosylation of proteins, peptides and amino acids. The methods utilise thiosulfonate or selenenylsulfide compounds as reagents or intermediates. Some proteins and peptides comprising selenenylsulfide groups also form part of the invention.
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Page/Page column 45-46
(2010/02/10)
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- Efficient stereoselective synthesis of γ-N-glycosyl asparagines by N-glycosylation of primary amide groups
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The efficient and elegant synthesis of N-glycosides by N-glycosylation of asparagine-containing peptides is described. Glycosylation of primary amides with glycosyl N-phenyltrifluoroimidates in the presence of a catalytic amount of TMSOTf in nitromethane
- Tanaka, Hiroshi,Iwata, Yuki,Takahashi, Daisuke,Adachi, Masaatsu,Takahashi, Takashi
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p. 1630 - 1631
(2007/10/03)
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- Bicyclic carbohydrates as antiviral bioactives for the treatment of infections caused by the alphaherpesvirinae HSV-1 and HSV-2
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Novel bicyclic carbohydrate compounds are effective for the prophylaxis and treatment of diseases caused by infections of the alphaherpesvirinae HSV-1 and HSV-2. The invention includes the compound wherein X1, X2, and X3 are selected from the group consisting of O, N, and S; wherein Y1 and Y2 are selected from the group consisting of O, N, and S; and wherein Z is selected from the group consisting of F, Cl, and Br, as well as analogs, prodrugs and pharmaceutically acceptable salts thereof, together with pharmaceutical compositions for the prophylaxis and treatment of diseases caused by infections of alphaherpesvirinae.
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Page/Page column 2
(2010/02/11)
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- Combinatorial synthesis of an oligosaccharide library by using β-bromoglycoside-mediated iterative glycosylation of selenoglycosides: Rapid expansion of molecular diversity with simple building blocks
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A new method for constructing an oligosaccharide library composed of structurally defined oligosaccharides is presented based on an iterative glycosylation of selenoglycosides. Treatment of 2-acyl-protected selenoglycosides with bromine selectively generates β-bromoglycosides, which serve as glycosyl cation equivalents in the oligosaccharide synthesis. Thus, the coupling of the bromoglycosides with another selenoglycoside affords the corresponding glycosylated selenoglycosides, which can be directly used to next glycosylation. The iteration of this sequence allows the synthesis of a variety of oligosaccharides including an elicitor active heptasaccharide. A characteristic feature of the iterative glycosylation is that glycosyl donors and acceptors with the same anomeric reactivity can be selectively coupled by activation of the glycosyl donor prior to coupling with the glycosyl acceptor. Therefore, same selenoglycosides can be used for both the glycosyl donors and the acceptors. This feature has been exemplified by a construction of an oligosaccharide library directed to elicitor-active oligosaccharides. The library composed of stereochemically defined oligoglucosides with considerable structural diversity can be constructed starting from simple selenoglycosides.
- Yamago, Shigeru,Yamada, Takeshi,Ito, Hiroki,Hara, Osamu,Mino, Yosuke,Yoshida, Jun-Ichi
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p. 6159 - 6174
(2007/10/03)
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- A convergent ring-closing metathesis approach to carbohydrate-based macrolides with potential antibiotic activity
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An efficient convergent approach has been developed for the construction of novel, non-natural, carbohydrate-based macrolides. The key step in the synthesis is the formation of the macrocyclic ring via a ring-closing metathesis reaction. The obtained macrolide analogues have been screened for biological activity against Gram-positive and Gram-negative bacteria, including resistant strains, yeasts, and molds.
- Blom, Petra,Ruttens, Bart,Van Hoof, Steven,Hubrecht, Idzi,Van Der Eycken, Johan,Sas, Benedikt,Van Hemel, Johan,Vandenkerckhove, Jan
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p. 10109 - 10112
(2007/10/03)
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- Bicyclic carbohydrate compounds useful in the treatment of infections caused by herpesviridae
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Bicyclic carbohydrates for the treatment of infections caused by herpseviridae, and in particular cytomegalovirus. The invention consists of the novel bicyclic carbohydrates the generic structure of which is: wherein R1 is either -Bn or -Ph; R2 and R3 are either -alkyl, -aryl, -allyl, or —H; R4 and R5 form a ring and are either —CH(Ph)- or —CH(aryl)- and X is either O, N or S.
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Page/Page column 5; 7
(2008/06/13)
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- Enantioselective Total Synthesis of Semperoside A
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A versatile and concise strategy has been developed (Scheme 1) for the enantioselective synthesis of semperoside A 1 which is endowed with an unusually glucosylated iridane structure. The crucial step was a Hg(II)-mediated electrophilic heteroatom cyclization of β-glucoside 4 that readily led to the iridane skeleton while installing the C-2 and C-3 stereocenters with complete stereocontrol. This expeditious route is unprecedented among synthetic approaches to iridoid glycosides and smoothly overcomes the hemiacetals glucosidation issue. The present inaugural total synthesis of semperoside A was achieved in 10 steps and 17% overall yield from the enantiomerically pure lactone 8, thus proving the absolute stereochemistry of 1 unequivocally. Copyright
- Piccinini, Paolo,Vidari, Giovanni,Zanoni, Giuseppe
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p. 5088 - 5089
(2007/10/03)
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- Glycosyl phenylthiosulfonates (glyco-PTS): novel reagents for glycoprotein synthesis.
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Controlled site-selective glycosylation can be achieved by combining site-directed cysteine mutagenesis with chemical modification of the introduced thiol; a new class of more efficient chemoselective reagents, glycosyl phenylthiosulfonates, allow rapid glycosylations of representative simple thiols, peptides and proteins.
- Gamblin, David P,Garnier, Philippe,Ward, Sarah J,Oldham, Neil J,Fairbanks, Antony J,Davis, Benjamin G
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p. 3642 - 3644
(2007/10/03)
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- Replacement of an anomeric hydroxyl group by a halogen atom using PdCl2/Et3SiH/halogen source system
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The anomeric hydroxyl group of perbenzylated and peracetylated carbohydrates can be stereoselectively replaced by a bromine or iodine atom using palladium dichloride, triethylsilane and carbon tetrabromide and/or iodine at room temperature. To illustrate the synthetic potential of this novel method, some models of O- and C-glycosides are reported. Reduction of sugar halide using excess of triethylsilane was not successful.
- Hassan,El-Husseiny
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p. 803 - 811
(2007/10/03)
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- The syntheses of 6-C-alkyl derivatives of methyl α-isomaltoside for a study of the mechanism of hydrolysis by amyloglucosidase
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The epimeric (6aR)- and (6aS)-C-alkyl (methyl, ethyl and isopropyl) derivatives of methyl α-isomaltoside (1) were synthesized in order to examine the effects of introducing alkyl groups of increasing bulk on the rate of catalysis for the hydrolysis of the interunit α-glycosidic bond by the enzyme amyloglucosidase, EC 3.2.1.3, commonly termed glucoamylase (AMG). It was previously established that methyl (6aR)-C-methyl α-isomaltoside is hydrolysed about 2 times faster than methyl α-isomaltoside and about 8 times faster than its S-isomer. The kinetics for the hydrolyses of the ethyl and isopropyl analogs were also recently published. As was expected from molecular model calculations, all the R-epimers are good substrates. A rationale is presented for the catalysis based on conventional mechanistic theories that includes the assistance for the decomposition of the activated complex to products by the presence of a hydrogen bond, which connects the 4a-hydroxyl group to the tryptophane and arginine units. It is proposed that activation of the initially formed complex to the transition state is assisted by the energy released as a result of both of the displacement of perturbed water molecules of hydration at the surfaces of both the polyamphiphilic substrate and the combining site and the establishment of intermolecular hydrogen bonds, i.e., micro-thermodynamics. The dissipation of the heat to the bulk solution is impeded by a shell of aromatic amino acids that surround the combining site. Such shields are known to be located around the combining sites of lectins and carbohydrate specific antibodies and are considered necessary to prevent the disruption of the intermolecular hydrogen bonds, which are of key importance for the stability of the complex. These features together with the exquisite stereoelectronic dispositions of the reacting molecules within the combining site offer a rationalization for the catalysis at ambient temperatures and near neutral pH. The syntheses involved the addition of alkyl Grignard reagents to methyl 6-aldehydo-α-D-glucopyranoside. The addition favoured formation of the S-epimers by over 90%. Useful amounts of the active R-isomers were obtained by epimerization of the chiral centers using conventional methods. Glycosylation of the resulting alcohols under conditions for bromide-ion catalysis, provided methyl (6aS)- and (6aR)-C-alkyl-hepta-O-benzyl-α-isomaltosides. Catalytic hydrogenolysis of the benzyl groups afforded the desired disaccharides. 1H NMR studies established the absolute configurations and provided evidence for conformational preferences.
- Spohr,Le,Ling,Lemieux
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p. 238 - 255
(2007/10/03)
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- C(2)-(α-Mannosyl)indole: The pivotal intermediate towards the natural C-Glycopeptides
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Two different approaches were investigated to prepare the unusual modified peptide C(2)-mannosylated indole residue. Direct glycosylation of 2-metallated indoles or 2-trimethylsilylindole derivative by reaction with perbenzylated α-D-mannopyranosyl bromid
- Hassan,Spies,Bredenkamp
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p. 1589 - 1598
(2007/10/03)
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- Rapid preparation of variously protected glycals using titanium(III)
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Glycosyl chlorides and bromides can be rapidly converted to glycals in high yield by reaction with (Cp2Ti[III]Cl)2. This reagent tolerates a wide range of common carbohydrate protecting groups, including silyl ethers, acetals, and esters; the methodology provides a general route for the preparation of glycals substituted with both acid- and base-labile functionality. A reaction mechanism is proposed that is based on heteroatom abstraction to give an intermediate glycosyl radical. This radical reacts with a second equivalent of Ti(III) to yield a glycosyltitanium(IV) species. β-Heteroatom elimination from the glycosyltitanium(IV) complex gives the glycal.
- Spencer, Roxanne P.,Cavallaro, Cullen L.,Schwartz, Jeffrey
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p. 3987 - 3995
(2007/10/03)
-
- Synthesis, NMR spectroscopy and conformational studies of the four anomeric methyl glycosides of the trisaccharide D-Glcp-(1→3)-[D-Glcp-(1→4)]-α-D-Glcp
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The four anomeric methyl glycosides of the vicinally disubstituted trisaccharide D-Glcp-(1→3)-[D-Glcp-(1→4)]-α-D-Glcp have been synthesized using silver trifluoromethanesulfonate mediated glycosylations. The 1H and 13C NMR resonances have been assigned and used for extraction of glycosylation shifts, i.e. the differences between chemical shifts for signals from the trisaccharides and those of the respective monomers, as well as those derived by addition of the glycosylation shifts for each disaccharide element. Glycosylation shifts are up to 0.5 ppm for proton and 10 ppm for carbon. Deviations from additivity are -0.2-0.1 ppm for proton and -4.5-2.3 ppm for carbon, usually confined to the atoms at the linkage positions. The conformational space spanned for the trisaccharides, and the constituent disaccharides, has been investigated by Metropolis Monte Carlo simulations using the HSEA force field. The α-linked glucosyl groups show larger conformational changes with multiple energy minima, whereas the β-linked glucosyl groups have a single energy minimum, close to that identified for the constituent disaccharide.
- Soederman, Peter,Jansson, Per-Erik,Widmalm, Goeran
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p. 639 - 648
(2007/10/03)
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- Synthesis of linear oligosaccharides: L-glycero-α-D-manno-heptopyranosyl derivatives of allyl α-glycosides of D-glucose, kojibiose, and 3-O-α-kojibiosyl-D-glucose, substrates for synthetic antigens
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Synthesis of the title oligosaccharides was performed with the use of peracetylated L-glycero-β-D-manno-heptosyl trichloroacetamidate as the heptosyl donor and (oligo)glucosyl acceptors bearing acyl and acetal protecting groups.
- Nepogod'ev, Sergey A.,Backinowsky, Leon V.,Grzeszczyk, Barbara,Zamojski, Aleksander
-
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- REACTION OF GLYCOSYL HALIDES WITH BENZYL GRIGNARD REAGENTS: UNEXPECTED o-TOLYL ALKYLATION OF TETRA-O-ACETYLGLUCOPYRANOSYL BROMIDE AND DIRECT SYNTHESIS OF (β-GLYCOSYL)PHENYLMETHANES
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The synthesis of (β-glycosyl)phenylmethanes by Grignard alkylation of glycosyl halides is investigated.Reaction of tetra-O-acetylglucopyranosyl bromide with benzylmagnesium chloride gave a good yield of a 3:1 mixture of 2-(β-D-glucopyranosyl)toluene and (β-glucosyl)phenylmethane.The requirement for an equatorial 2-acetoxy group and 6-acetoxymethyl group for the formation of the unexpected o-tolyl rearrangement product is explored by using xylosyl, mannosyl, and 2-deoxyglucosyl halides as substrates for the alkylation.Synthesis of (β-glucosyl)phenylmethane by alkylation of 2,3,4,6-tetra-O-benzylglucosyl bromide with benzylmagnesium chloride is also presented.
- Panigot, Michael J.,Curley, Robert W.
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p. 293 - 302
(2007/10/02)
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- Inhibitors of endo-α-mannosidase. Part II. 1-Deoxy-3-O-(α-D-glucopyranosyl)-mannojirimycin and congeners modified in the mannojirimycin unit
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The syntheses of 1-deoxy-3-O-(α-D-glucopyranosyl)-mannojirimycin (9) and its 2-deoxy, 2-O-methyl, 4-deoxy, 4-O-methyl, 6-deoxy, 6-O-methyl, N-methyl, and N-propyl congeners are described. Since 9 was previously shown to effectively inhibit endo-α-D-mannosidase, a glycoprotein-processing hydrolase, these chemical modifications were designed to assist in the assessment of intermolecular hydrogen bonds of the inhibitor-enzyme complex. The previously reported data require that all hydroxyl groups of the deoxymannojirimycin unit of 9 namely, OH-2, OH-4, OH-6, and also the NH-5 group, interact with charged and polar groupings of the enzyme since deoxygenations and alkylations abolished or significantly reduced activities. Conformational analysis of 9 and some of its congeners based on NMR chemical shifts, experimental and theoretical nuclear Overhauser enhancements and HSEA calculations were performed. The chemical modifications of the glucose unit of 9 are described in the accompanying paper.
- Spohr,Bach,Spiro
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p. 1928 - 1942
(2007/10/02)
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- Process for the preparation of protected mono-sugar and oligo-sugar halides
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The reaction of protected monosaccharides or oligosaccharides or protected monosaccharide and oligosaccharide derivatives containing an anomeric hydroxyl group with secondary α-haloenamines affords high yields of protected glycosyl halides, which are valuable intermediates for the introduction of sugar groups in the synthesis of oligosaccharides, glycolipids or glycopeptides.
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- Synthesis and NMR and Conformational Studies of the Four Anomeric Methyl Glycosides of the Trisaccharide D-Glcp-(1->2)-D-Glcp-(1->3)-α-D-Glcp
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The four anomeric methyl glycosides of the trisaccharide D-Glcp-(1->2)-D-Glcp-(1->3)-α-D-Glcp have been synthesized and used for 1H and 13C NMR studies.All 1H and 13C NMR resonances were assigned and comparison was made between the observed glycosylation shifts, i.e. the differences between chemical shifts for signals from the trisaccharides and those of the respective monomers, and those derived by addition of the glycosylation shifts for each disaccharide element.With a few exceptions, only minor deviations were found and the differences were mostly confined to signals from linkage carbons and the attached protons.Conformational analysis was performed using the HSEA and GESA approaches and measurements of the nuclear Overhauser enhancements.The results indicate that minimum energy conformations are similar to those of the disaccharides but that rotational freedom around some of the glycosidic bonds is restricted.
- Adeyeye, Adenrele,Jansson, Per-Erik,Kenne, Lennart,Widmalm, Goeran
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p. 963 - 973
(2007/10/02)
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- Generation of α-D-Glucopyranosylacetonitrilium Ions. Concerning the Reverse Anomeric Effect
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Reaction of the α- and β-anomers of the pent-4-enyl D-glucopyranoside (10) with N-bromosuccinimide in dry acetonitrile generated stereospecifically the α-D-glucopyranosylacetonitrilium ion (5α), which reacts in situ with 2-chlorobenzoic acid to afford the α-imide (8α).The result is in contrast to that predicted by the reverse anomeric effect and previous work on trapping carbohydrate acetonitrilium ions with 2-chlorobenzoic acid.The unusually large J12 7.3 Hz for 1-H of (8α) is rationalised by a substantial flattening of the pyranose ring at C-1 and C-2.Molecular dynamic studies on the model α-imide (12) support a flattened 4C1 conformation.Treatment of imide (8α) with sodium methoxide leads to the α-2-chlorobenzamide (9α), which was substantiated by intependent synthesis of the β-2-chlorobenzamide (9β).
- Ratcliffe, Andrew J.,Fraser-Reid, Bert
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p. 747 - 750
(2007/10/02)
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- Conversion of Pent-4-enyl Glycosides into Glycosyl Bromides
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The unique features of pent-4-enyl glycosides for chemospecific (a) protection and (b) activation of the anomeric centre have been exploited for the preparation of glycosyl bromides under such mild conditions that oxidable and acid sensitive protecting groups are not affected, and in such excellent yields that the product can be used in situ for saccharide coupling.
- Konradsson, Peter,Fraser-Reid, Bert
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p. 1124 - 1125
(2007/10/02)
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- PREPARATION OF GLYCOSYL HALIDES UNDER NEUTRAL CONDITIONS
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The anomeric hydroxyl group of various furanose and pyranose hemiacetals can be replaced by a fluorine, chlorine, bromine or iodine atom under neutral conditions using haloenamines.
- Ernst, Beat.,Winkler, Tammo.
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p. 3081 - 3084
(2007/10/02)
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- Alkynylation of Mixed Acetals with Organotin Acetylides
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Reaction of halo acetals containing O, N, or S heteroatoms with tri-n-butyltin acetylides in the presence of ZnCl2 in CCl4 leads to the formation of α-alkynyl ethers, amines, and sulfides in good yields.The methodology is exemplified with the synthesis of amino acids and C-glycosides.
- Zhai, Dongguan,Zhai, Weixu,Williams, Robert M.
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p. 2501 - 2505
(2007/10/02)
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- Synthesis of C-Glucosides by Reactions of Glucosyl Halides with Organocuprates.
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Lithium dimethylcuprate reacts with trans-2-chloro-6-methyltetrahydropyran (1) via nucleophilic substitution predominantly with inversion of configuration to afford cis-2,6-dimethyltetrahydropyran (2).Similarly, lithium dialkylcuprates displace protected α-glucosyl bromides (5) with inversion to afford the β-C-glucosides, β-1-alkyl-1,5-anhydroglucitols (6).In contrast, Grignard reagents gave mixtures of α- and β- glucosides 6 and 7, while organolithium reagents gave only elimination to 9.
- Bihovsky Ron,Selick Caryn,Giusti Irena
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p. 4026 - 4031
(2007/10/02)
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- SYNTHESIS OF 6-O-α-D-GLUCOPYRANOSYLCYCLOMALTOHEPTAOSE
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(2,3-Di-O-acetyl)hexakis(2,3,6-tri-O-acetyl)cyclomaltoheptaose was prepared by reaction of cyclomaltoheptaose with tert-butyldimethylsilyl chloride in pyridine followed by acetylation and desilylation.Glycosylation with 2,3,4,6-tetra-O-benzoyl-1-O-trichloroacetimidoyl-α-D-glucopyranose, using trifluoromethanesulfonic acid as catalyst, and removal of the protecting groups from the product then afforded the title compound.
- Fuegedi, Peter,Nanasi, Pal,Szejtli, Jozsef
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p. 173 - 182
(2007/10/02)
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- The Treatment of Some Carbohydrate Alcohols and Diols with N-Dibromomethylene-N,N-dialkylammonium Bromides: a Synthesis of Glycosyl Bromides
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Two analogues of Viehe's salt (Me2N+=CCl2 Cl-), namely Me2N+=CBr2 Br- and Et2N+=CBr2 Br-, were prepared and treated with various carbohydrate alcohols and diols.With the diols, the products formed corresponded to those previously obtained with Viehe's salt itself, namely bromo deoxy sugars, cyclic carbonates or carbamates, and depended on the nature of the substrate and the reaction conditions.With the alcohols, mainly free sugars, a useful synthesis of glycosyl bromides was achieved.
- McAdam, David P.,Stick, Robert V.
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p. 563 - 573
(2007/10/02)
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- Synthesis of phosphatidyl-α-glucosyl glycerol containing a dioleoyl phosphatidyl moiety. Application of the tetraisopropyldisiloxane-1,3-diyl (tips) protecting group in sugar chemistry. part III1 1 For part I and II see references 11 and 39, respectively.
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In this study we demonstrate that the tetraisopropyldisiloxane-1,3-diyl protecting group could be introduced, in a two step procedure, at the 3'- and 4'-hydroxyl functions of α-glucosyldiglyceride 3 to give derivative 6. Compound 6 could be selectively condensed with a suitably protected phosphatidyl part 9 at its primary hydroxyl function to afford the protected glycophospholipid 10a. The phosphatidyl part 9 was obtained by phosphorylation of optically pure 1,2-di-O-oleoyl-sn-glycerol (8a) with phosphoditriazolide 7b. Finally, the 2,4-dichlorophenyl and TIPS protecting groups were removed from 10a by syn-4-nitro-benzaldoximate and fluoride ions, respectively, to afford glycophospholipid 10c.
- van Boeckel,van Boom
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p. 4545 - 4555
(2007/10/02)
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