Assembly of a Complex Branched Oligosaccharide by Combining Fluorous‐Supported Synthesis and Stereoselective Glycosylations using Anomeric Sulfonium Ions

Huang, Wei; Gao, Qi; Boons, Geert‐Jan

doi:10.1002/chem.201501844

Cited by 26 publications

(7 citation statements)

References 56 publications

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“…The unique properties of perfluoroalkyl chains (aka. fluorous tags), which show a high affinity toward the fluorous-phase surface, have made the FSPE an attractive product purification technique. , Fluorous tag-assisted chemical syntheses are proven to be efficient for the preparation of complex oligosaccharides, , and these have further led to multistep automated processes. , The wide applications of the fluorous tag on glycan microarray fabrication, enzyme assay platform, and enzymatic glycan synthesis − have also been demonstrated. The design of SF 17 originated from the SOFA tag in which the sulfonate moiety enhanced the water solubility of the fluorous (C 8 F 17 )-tagged acceptors …”

Section: Resultsmentioning

confidence: 99%

Sulfo-Fluorous Tagging Strategy for Site-Selective Enzymatic Glycosylation of para-Human Milk Oligosaccharides

Huang

et al. 2021

ACS Catal.

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In this study, we developed an efficient fluorous tagging strategy for site-selective enzymatic fucosylation/sialylation in which appending a readily removable auxiliary tag (SF 17 ) to the reducing end of an acceptor provided the regioselectivity control of a given wild-type fucosyltransferase/sialyltransferase. By combining this strategy with the sequential one-pot enzymatic system of HMO production, various fucosylated para-HMOs, such as LNFP I, LNFP II, LNFP III, LNFP V, LNDFH I, LNDFH II, TF-LNT, F-pLNH I, F-pLNH IV, DF-pLNH I isomer, DF-pLNH II, TF-pLNH I, TF-pLNH II, F-pLNnH, F-pLNnH I, DF-pLNnH, TF-pLNnH, and TetraF-pLNO, were synthesized. Furthermore, the SF 17 -tagged acceptors improved the reaction rates of the enzymatic glycan chain extension. Terminal α2,6-sialylation on SF 17 -tagged pLNnH was directly achieved using wild-type α2,6-sialyltransferase from Photobacterium damsela (Pd26ST). Moreover, enzyme kinetics revealed that the catalytic efficiency (k cat/K M) of α1,4-fucosylation of Bf13FT (α1,3/4-fucosyltransferase from Bacteroides fragilis) on SF 17 -tagged LNFP V acceptors could be enhanced by 55 times compared with tagging with an azidohexyl aglycone. We developed an efficient and reliable strategy for generating complex and diverse natural HMO libraries for functional gut microbiome studies. This SF 17 -assisted glycosylation strategy provides a practical approach to harness the extreme substrate flexibility offered by readily available bacterial glycosyltransferases, which enables the site-selective fucosylation/sialylation on para-HMOs.

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Section: Resultsmentioning

confidence: 99%

Sulfo-Fluorous Tagging Strategy for Site-Selective Enzymatic Glycosylation of para-Human Milk Oligosaccharides

Huang

et al. 2021

ACS Catal.

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“…Solution-phase synthesis with a substrate bound to water-soluble [224] or thermo-responsive polymers [225], fluorous- [217,226,227,228,229,230,231,232,233,234,235,236], ion exchange [237], or lipid-like tags [238] has attracted much interest since it can bypass compatibility issues between enzymes and solid carriers. The main disadvantage of solution-phase assembly of oligosaccharides catalyzed by glycosyltransferases is the low catalytic efficiency and affinity for the substrates due to different steric and stereoelectronic properties induced by the substrate-bound tag.…”

Section: Reactor Engineering For (Non)-leloir Glycosyltransferasesmentioning

confidence: 99%

Leloir Glycosyltransferases in Applied Biocatalysis: A Multidisciplinary Approach

Mestrom

Przypis

Kowalczykiewicz

et al. 2019

IJMS

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Enzymes are nature's catalyst of choice for the highly selective and efficient coupling of carbohydrates. Enzymatic sugar coupling is a competitive technology for industrial glycosylation reactions, since chemical synthetic routes require extensive use of laborious protection group manipulations and often lack regio-and stereoselectivity. The application of Leloir glycosyltransferases has received considerable attention in recent years and offers excellent control over the reactivity and selectivity of glycosylation reactions with unprotected carbohydrates, paving the way for previously inaccessible synthetic routes. The development of nucleotide recycling cascades has allowed for the efficient production and reuse of nucleotide sugar donors in robust one-pot multi-enzyme glycosylation cascades. In this way, large glycans and glycoconjugates with complex stereochemistry can be constructed. With recent advances, LeLoir glycosyltransferases are close to being applied industrially in multi-enzyme, programmable cascade glycosylations.hydroxynitrile lyases catalyzed the enzymatic hydrolysis of the glycoside amygdalin [3]. Moving almost two centuries forward, the largest volumetric biocatalytic industrial process is the application of glucose isomerase for the production of high fructose syrup for food and drink applications, producing fructose from glucose at 10 7 tons per year [4]. The secret of the success of enzymes in the production or treatment of carbohydrates and glycosides is their exquisite stereo-and regioselectivity. The excellent selectivity of enzymes is required due to the diversity of structural features of carbohydrates [5], comprising d-and l-epimers, ring size, anomeric configuration, linkages, branching, and oxidation state(s). Since drug targets often exhibit specificity for all of these structural features, the production process should not contain any side-products to prevent undesired side-effects [6].The challenge in the synthesis of carbohydrates is their wide variety of functionalities and stereochemistry ( Figure 1). (Poly)hydroxyaldehydes containing a terminal aldehyde are referred to as aldoses and (poly)hydroxyketones are defined as ketoses. In aqueous solutions, monosaccharides form equilibrium mixtures of linear open-chain and ring-closed 5-or 6-membered furanoses or pyranoses, respectively. For aldoses, the asymmetric ring forms at C-1. For ketoses, it closes at C-2 as an axial (α) or equatorial (β) hemiacetal or hemiketal, respectively (commonly defined as the anomeric center). A glycosidic linkage is a covalent O-, S-, N-, or C-bond connecting a monosaccharide to another residue resulting in a glycoside, while glucoside is specific for a glucose moiety. The equatorial or axial position of the glycosidic bond is referred to as α-(axial) or β-linkage (equatorial). The number of carbohydrates linked via glycosidic bonds can be subdivided into oligosaccharides with two to ten linked carbohydrates, while polysaccharides (glycans) contain more than ten glycosidic bonds. A glycan either con...

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“…Both the oxathiane donor and donor bearing a C‐2 ( S )‐phenylthiomethylbenzyl ether were employed for the synthesis of oligosaccharide 149 found on the glycosylphosphatidylinositol (GPI) anchor of Trypanosoma brucei , a parasite that causes sleeping sickness in humans and similar diseases in domestic animals (Scheme ) . Hexasaccharide 149 from T. brucei consists of four galactose and two mannose monomers all linked by α‐glycosidic bonds.…”

Section: Application To Complex Oligosaccharide Synthesismentioning

confidence: 99%

Advances in Stereoselective 1,2‐cisGlycosylation using C‐2 Auxiliaries

Mensink

Boltje

2017

Chemistry A European J

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The control of stereoselectivity in a glycosylation reaction remains one of the most challenging aspects of oligosaccharide synthesis. Especially the synthesis of 1,2-cis-glycosides is challenging and generally applicable methodology to prepare this linkage is needed to standardize oligosaccharide synthesis. This review highlights the recent development of an elegant strategy employing a C-2 auxiliary to control the anomeric stereoselectivity in glycosylations. The various auxiliaries developed to date, their compatibility with protecting groups and monosaccharide types as well as mechanistic aspects are summarized. Furthermore, the application, advantages and limitations of C-2 auxiliaries in oligosaccharide synthesis are discussed.

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Assembly of a Complex Branched Oligosaccharide by Combining Fluorous‐Supported Synthesis and Stereoselective Glycosylations using Anomeric Sulfonium Ions

Cited by 26 publications

References 56 publications

Sulfo-Fluorous Tagging Strategy for Site-Selective Enzymatic Glycosylation of para-Human Milk Oligosaccharides

Sulfo-Fluorous Tagging Strategy for Site-Selective Enzymatic Glycosylation of para-Human Milk Oligosaccharides

Leloir Glycosyltransferases in Applied Biocatalysis: A Multidisciplinary Approach

Advances in Stereoselective 1,2‐cisGlycosylation using C‐2 Auxiliaries

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