The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Peter H. Seeberger - One of the best experts on this subject based on the ideXlab platform.
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automated glycopeptide assembly by combined solid phase peptide and Oligosaccharide Synthesis
Chemical Communications, 2014Co-Authors: Mattan Hurevich, Peter H. SeebergerAbstract:Current strategies for the Synthesis of glycopeptides require multiple manual synthetic steps. Here, we describe a Synthesis concept that merges solid phase peptide and Oligosaccharide syntheses and can be executed automatically using a single instrument.
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Oligosaccharide Synthesis in microreactors
Organic Letters, 2007Co-Authors: Frederic R Carrel, Jeroen D C Codee, Karolin Geyer, Peter H. SeebergerAbstract:Described is the combination of microreactors and fluorous phase chemistry to assemble Oligosaccharides. The Synthesis of a beta-(1-->6) linked D-glucopyranoside homotetramer serves to illustrate this approach. Glycosylations employing a Fmoc-protected glucosyl phosphate building block were performed in a silicon-based micro-structured device to optimize reaction conditions and for reaction scale-up. A perfluorinated linker at the reducing end of the Oligosaccharides allowed for purification by fluorous solid-phase extraction (FSPE) and further functionalization.
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automated Synthesis of the tumor associated carbohydrate antigens gb 3 and globo h incorporation of α galactosidic linkages
Journal of the American Chemical Society, 2007Co-Authors: Daniel B Werz, Bastien Castagner, Peter H. SeebergerAbstract:The Globo series of tumor-associated antigens are glycosphingolipids implicated in several cancer types. These Oligosaccharides contain an α-linked galactose. Reported are methods to efficiently install cis-galactosidic linkages by automated solid-phase Oligosaccharide Synthesis. The complex tumor-associated Oligosaccharides Globo-H and Gb-3 were assembled in about 1 day using the new approach that extends the scope of automated Oligosaccharide Synthesis to structurally more challenging carbohydrates.
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rapid Synthesis of a glycosylphosphatidylinositol based malaria vaccine using automated solid phase Oligosaccharide Synthesis
Journal of the American Chemical Society, 2002Co-Authors: Michael C Hewitt, Daniel A Snyder, Peter H. SeebergerAbstract:Described is an automated Synthesis of hexasaccharide malarial toxin 1, currently under development as a malaria vaccine candidate. Using a combination of automated solid-phase methods and solution-phase fragment coupling, the target glycosylphosphatidylinositol was assembled in a matter of days, compared with several weeks for a comparable solution-phase Synthesis.
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Oligosaccharide Synthesis with glycosyl phosphate and dithiophosphate triesters as glycosylating Agents
Journal of the American Chemical Society, 2001Co-Authors: Obadiah J. Plante, Emma R. Palmacci, Rodrigo B. Andrade, Peter H. SeebergerAbstract:Described is an efficient one-pot Synthesis of alpha- and beta-glycosyl phosphate and dithiophosphate triesters from glycals via 1,2-anhydrosugars. Glycosyl phosphates function as versatile glycosylating agents for the Synthesis of beta-glucosidic, beta-galactosidic, alpha-fucosidic, alpha-mannosidic, beta-glucuronic acid, and beta-glucosamine linkages upon activation with trimethylsilyl trifluoromethanesulfonate (TMSOTf). In addition to serving as efficient donors for O-glycosylations, glycosyl phosphates are effective in the preparation of S-glycosides and C-glycosides. Furthermore, the acid-catalyzed coupling of glycosyl phosphates with silylated acceptors is also discussed. Glycosyl dithiophosphates are synthesized and are also used as glycosyl donors. This alternate method offers compatibility with acceptors containing glycals to form beta-glycosides. To minimize protecting group manipulations, orthogonal and regioselective glycosylation strategies with glycosyl phosphates are reported. An orthogonal glycosylation method involving the activation of a glycosyl phosphate donor in the presence of a thioglycoside acceptor is described, as is an acceptor-mediated regioselective glycosylation strategy. Additionally, a unique glycosylation strategy exploiting the difference in reactivity of alpha- and beta-glycosyl phosphates is disclosed. The procedures outlined here provide the basis for the assembly of complex Oligosaccharides in solution and by automated solid-phase Synthesis with glycosyl phosphate building blocks exclusively or in concert with other donors.
Geertjan Boons - One of the best experts on this subject based on the ideXlab platform.
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opportunities and challenges in synthetic Oligosaccharide and glycoconjugate research
ChemInform, 2010Co-Authors: Thomas J Boltje, Therese Buskas, Geertjan BoonsAbstract:Synthetic Oligosaccharides and glycoconjugates are increasingly used as probes for biological research and as lead compounds for drug and vaccine discovery. These endeavors are, however, complicated by a lack of general methods for the routine preparation of this important class of compounds. Recent development such as one-pot multi-step protecting group manipulations, the use of unified monosaccharide building blocks, the introduction of stereoselective glycosylation protocols, and convergent strategies for Oligosaccharide assembly, are beginning to address these problems. Furthermore, Oligosaccharide Synthesis can be facilitated by chemo-enzymatic methods, which employ a range of glycosyl transferases to modify a synthetic Oligosaccharide precursor. Glycosynthases, which are mutant glycosidases, that can readily form glycosidic linkages are addressing a lack of a wide range glycosyltransferases. The power of carbohydrate chemistry is highlighted by an ability to synthesize glycoproteins.
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Synthesis of Oligosaccharides on soluble high molecular weight branched polymers in combination with purification by nanofiltration
Organic Letters, 2003Co-Authors: Debatosh Majumdar, Tong Zhu, Geertjan BoonsAbstract:An efficient approach for polymer-supported Oligosaccharide Synthesis is described whereby branched and high-molecular-weight PEG derivatives are used in combination with purification by nanofiltration. This methodology was applied to the preparation of a tetraglucoside and the tumor-associated antigen Lex.
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the 2 allyloxy phenyl acetyl ester as a new relay protecting group for Oligosaccharide Synthesis
Tetrahedron Letters, 2001Co-Authors: Esther Arranz, Geertjan BoonsAbstract:Abstract The 2-(allyloxy) phenyl acetyl group can be removed by a relay approach using Pd(PPh 3 ) 4 in combination with proton sponge, conditions that do not affect acetyl, benzoyl and levulinoyl esters. On the other hand, the acetyl and levulinoyl ester could be cleaved without removal of the 2-(allyloxy) phenyl acetyl group. The new protecting group is compatible with glycosylations and can perform efficiently neighboring group participation leading to the exclusive formation of 1,2- trans glycosides.
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polystyrylboronic acid as a reusable polymeric support for Oligosaccharide Synthesis
Tetrahedron Letters, 2000Co-Authors: Gianluca Belogi, Tong Zhu, Geertjan BoonsAbstract:Abstract Polystyrylboronic acid is an attractive polymeric support for Oligosaccharide Synthesis that can easily be prepared in high loading capacity and re-used after a synthetic sequence. Saccharides were loaded by heating in pyridine and released by treatment with a mixture of acetone and water. NIS/TMSOTf mediated glycosidations of thioglycosides gave a quantitative formation of disaccharides.
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a new set of orthogonal protecting groups for Oligosaccharide Synthesis on a polymeric support
Tetrahedron-asymmetry, 2000Co-Authors: Tong Zhu, Geertjan BoonsAbstract:Abstract The hydroxyl-protecting groups, levulinoyl (Lev) and 9-fluorenylmethoxycarbonyl (Fmoc), and the amino-protecting group 2,2,2-trichloroethoxycarbonyl (Troc), offer an ideal set of orthogonal-protecting groups which are compatible with Oligosaccharide Synthesis on a methylpolyethyleneglycol (MPEG) support using a p -alkyloxybenzyl-type linker.
Mitsuo Takai - One of the best experts on this subject based on the ideXlab platform.
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regioselective syntheses of new tri and tetrasaccharides from β glucobioses by trichoderma viride β glucosidase and their structural analyses by nmr spectroscopy
Carbohydrate Research, 1999Co-Authors: Hiroyuki Kono, Tomoki Erata, Markus R Waelchili, Masashi Fujiwara, Mitsuo TakaiAbstract:Abstract A new β-glucosidase was partially purified from Trichoderma viride cellulase complex. This β-glucosidase hydrolyzed β-(1→2)-, β-(1→3)-, β-(1→4)-, and β-(1→6)-linked glucobioses and catalyzed a transglycosylation reaction of cellobiose to give regioselectively β- d -Glc-(1→6)-β- d -Glc-(1→4)- d -Glc (yield: 18.8%) and β- d -Glc-(1→6)-β- d -Glc-(1→6)-β- d -Glc-(1→4)- d -Glc (3.7%). Furthermore, the enzyme converted laminarabiose and gentiobiose into β- d -Glc-(1→6)-β- d -Glc-(1→3)- d -Glc (15.3%) and β- d -Glc-(1→6)-β- d -Glc-(1→6)- d -Glc (20.2%), respectively. The structures of the products were determined by 1 H and 13 C NMR spectroscopy. This high regio- and stereoselectivity demonstrated by the enzyme could be applied for Oligosaccharide Synthesis in general.
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structural analyses of new tri and tetrasaccharides produced from disaccharides by transglycosylation of purified trichoderma viride β glucosidase
Glycoconjugate Journal, 1999Co-Authors: Hiroyuki Kono, Shin Kawano, Kenji Tajima, Tomoki Erata, Mitsuo TakaiAbstract:A new β-glucosidase was partially purified from Trichoderma viride cellulase. This β-glucosidase catalyzed a transglycosylation reaction of cellobiose to give β-D-Glc-(1→6)-β-D-Glc-(1→4)-D-Glc (1, yield: 18.8%) and β-D-Glc-(1→6)-β-D-Glc-(1→6)-β-D-Glc-(1→4)-D-Glc (2, 3.7%), regioselectively. Furthermore, the enzyme regioselectively converted laminaribiose and gentiobiose into β-D-Glc-(1→6)-β-D-Glc-(1→3)-D-Glc (3, 15.3%) and β-D-Glc-(1→6)-β-D-Glc-(1→6)-D-Glc (4, 20.2%), respectively. The structures (1–4) of the products were determined by 1H and 13C NMR spectroscopies. This high regio- and stereoselectively of the β-glucosidase could be applied for Oligosaccharide Synthesis.
Chihuey Wong - One of the best experts on this subject based on the ideXlab platform.
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Oligosaccharide Synthesis and translational innovation
Journal of the American Chemical Society, 2019Co-Authors: Larissa B Krasnova, Chihuey WongAbstract:The translation of biological glycosylation in humans to the clinical applications involves systematic studies using homogeneous samples of Oligosaccharides and glycoconjugates, which could be accessed by chemical, enzymatic or other biological methods. However, the structural complexity and wide-range variations of glycans and their conjugates represent a major challenge in the Synthesis of this class of biomolecules. To help navigate within many methods of Oligosaccharide Synthesis, this Perspective offers a critical assessment of the most promising synthetic strategies with an eye on the therapeutically relevant targets.
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toward automated Oligosaccharide Synthesis
ChemInform, 2012Co-Authors: Chihuey Wong, Chehsiung Hsu, Shangcheng HungAbstract:Carbohydrates have been shown to play important roles in biological processes. The pace of development in carbohydrate research is, however, relatively slow due to the problems associated with the complexity of carbohydrate structures and the lack of general synthetic methods and tools available for the study of this class of biomolecules. Recent advances in Synthesis have demonstrated that many of these problems can be circumvented. In this Review, we describe the methods developed to tackle the problems of carbohydrate-mediated biological processes, with particular focus on the issue related to the development of the automated Synthesis of Oligosaccharides. Further applications of carbohydrate microarrays and vaccines to human diseases are also highlighted.
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n phenylthio e caprolactam a new promoter for the activation of thioglycosides
Organic Letters, 2004Co-Authors: Sergio G Duron, Tulay Polat, Chihuey WongAbstract:N-(Phenylthio)-e-caprolactam (1) has been applied as a new promoter for the activation of thioglycosides. This proceeds by the reaction of 1 with trifluoromethansulfonic anhydride, which subsequently activates the thioglycoside for glycosidic bond formation. Notably, the reaction proceeds efficiently at room temperature and is adaptable to our reactivity-based one-pot Oligosaccharide Synthesis.
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anomeric reactivity based one pot Oligosaccharide Synthesis a rapid route to Oligosaccharide libraries
ChemInform, 2000Co-Authors: Chihuey WongAbstract:The assembly of an Oligosaccharide library has been achieved in a practical and efficient manner employing a' one-pot sequential approach. With the help of the anomeric reactivity values of thioglycosides, using a thioglycoside (mono- or disaccharide) with one free hydroxyl group as acceptor and donor coupled with another fully protected thioglycoside, a di- or trisaccharide is selectively formed without self-condensation and subsequently reacted in situ with an anomerically inactive glycoside (mono- or disaccharide) to form a tri- or tetrasaccharide in high overall yield. The approach enables the rapid assembly of 33 linear or branched fully protected Oligosaccharides using designed building blocks. These fully protected Oligosaccharides have been partially or completely deprotected to create 29 more structures to further increase the diversity of the library.
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Regeneration of sugar nucleotide for enzymatic Oligosaccharide Synthesis.
Methods in enzymology, 1994Co-Authors: Yoshitaka Ichikawa, Ruo Wang, Chihuey WongAbstract:Publisher Summary Glycosyltransferase-mediated Oligosaccharide Synthesis is of current interest in synthetic carbohydrate chemistry. Although the enzymatic method is regio- and stereoselective and does not require multiple protection and deprotection steps, it is still hampered by the unavailability of transferases, the problem of product inhibition in stoichiometric reactions, and the tedious preparation of the donor substrate sugar nucleotides when large-scale processes are needed. Although many glycosyltransferases are involved in the bioSynthesis of Oligosaccharides, these enzymes utilize only eight sugar nucleotides as donor substrates in mammalian systems. Development of regeneration systems for each of these sugar nucleotides would therefore make possible the practical Synthesis of most complex Oligosaccharides, provided that glycosyltransferases are available.
Clay S Bennett - One of the best experts on this subject based on the ideXlab platform.
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matching glycosyl donor reactivity to sulfonate leaving group ability permits sn2 glycosylations
Journal of the American Chemical Society, 2019Co-Authors: Minghua Zhuo, David J Wilbur, Eugene E Kwan, Clay S BennettAbstract:Here we demonstrate that highly β-selective glycosylation reactions can be achieved when the electronics of a sulfonyl chloride activator and the reactivity of a glycosyl donor hemiacetal are matched. While these reactions are compatible with the acid- and base-sensitive protecting groups that are commonly used in Oligosaccharide Synthesis, these protecting groups are not relied upon to control selectivity. Instead, β-selectivity arises from the stereoinversion of an α-glycosyl arylsulfonate in an SN2-like mechanism. Our mechanistic proposal is supported by NMR studies, kinetic isotope effect (KIE) measurements, and DFT calculations.
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Challenges in the Conversion of Manual Processes to Machine-Assisted Syntheses: Activation of Thioglycoside Donors with Aryl(trifluoroethyl)iodonium Triflimide
2018Co-Authors: Regis C. Saliba, Clay S Bennett, Anhsiang Adam Chu, Zachary J. Wooke, Gabriel A. Nieves, Nicola L B PohlAbstract:The steps needed to adapt a stable iodonium promoter for use in automated fluorous-assisted solution-phase Oligosaccharide Synthesis are described. Direct adaptation of the originally reported batch procedure resulted in the formation of an orthoester or protecting group transfer to the glycosyl acceptor. Fortunately, the addition of inexpensive β-pinene as an acid scavenger avoided both of these side reactions. The utility of this newly developed protocol was applied to the automated solution-phase Synthesis of a β-glucan fragment
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principles of modern solid phase Oligosaccharide Synthesis
ChemInform, 2014Co-Authors: Clay S BennettAbstract:The past few decades have seen a renewed interest in the chemical Synthesis of Oligosaccharides, owing to increased recognition of their biological importance. Of the different approaches to Oligosaccharides, solid-phase Synthesis has emerged as a particularly attractive option, due in large part to its potential for automation. This perspective describes principles to consider when planning solid-phase Oligosaccharide Synthesis (SPOS), including recent achievements and areas where future work is necessary.
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selective Synthesis of 1 2 cis α glycosides without directing groups application to iterative Oligosaccharide Synthesis
Organic Letters, 2013Co-Authors: Anhsiang Adam Chu, Son Hong Nguyen, Jordan A Sisel, Andrei Minciunescu, Clay S BennettAbstract:A method for the highly selective Synthesis of 1,2-cis-α-linked glycosides that does not require the use of the specialized protecting group patterns normally employed to control diastereoselectivity is described. Thioglycoside acceptors can be used, permitting iterative Oligosaccharide Synthesis. The approach eliminates the need for lengthy syntheses of monosaccharides possessing highly specialized and unconventional protecting group patterns.
