Browsing by Author "Hung, Shang-Cheng"

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2-Allylphenyl glycosides as glycosyl donors for sugar coupling
(2012-05-01)
Luo, Shun-Yuan
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Tripathi, Ashish
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Zulueta, Medel Manuel L.
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Hung, Shang-Cheng
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應用化學系
Glycosylations employing 2-allylphenyl glycoside, a new type of stable glycosyl donor, were optimized and explored with a variety of acceptors promoted by ICl/AgOTf. The utility of the protocol was further demonstrated with an efficient synthesis of the disaccharide fragment of bleomycins. (C) 2012 Elsevier Ltd. All rights reserved.
Acyl and Silyl Group Effects in Reactivity-Based One-Pot Glycosylation: Synthesis of Embryonic Stem Cell Surface Carbohydrates Lc(4) and IV(2)Fuc-Lc(4)
(2012-03-14)
Hsu, Yun
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Lu, Xin-An
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Zulueta, Medel Manuel L.
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Tsai, Chih-Ming
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Lin, Kuo-I
Relative reactivity evaluations showed the graded arming of toluenyl thioglucosides by variously positioned silyl groups but not by their acyl counterparts. These findings were applied in reactivity-based one-pot assembly of linker-attached Lc(4) and IV(2)Fuc-Lc(4), which are components of human embryonic stem cell surface. The sugar-galectin-1 binding was also examined.
alpha-Glycosylation by D-Glucosamine-Derived Donors: Synthesis of Heparosan and Heparin Analogues That Interact with Mycobacterial Heparin-Binding Hemagglutinin
(2012-05-30)
Zulueta, Medel Manuel L.
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Lin, Shu-Yi
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Lin, Ya-Ting
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Huang, Ching-Jui
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Wang, Chun-Chih
Numerous biomolecules possess alpha-D-glucosamine as structural component. However, chemical glycosylations aimed at this backbone are usually not easily attained without generating the unwanted beta-isomer. We report herein a versatile approach in affording full alpha-stereoselectivity built upon a carefully selected set of orthogonal protecting groups on a D-glucosaminyl donor. The excellent stereoselectivity provided by the protecting group combination was found independent of leaving groups and activators. With the trichloroacetimidate as the optimum donor leaving group, core skeletons of glycosylphosphatidyl inositol anchors, heparosan, heparan sulfate, and heparin were efficiently assembled. The orthogonal protecting groups were successfully manipulated to further carry out the total syntheses of heparosan tri- and pentasaccharides and heparin di-, tetra-, hexa-, and octasaccharide analogues. Using the heparin analogues, heparin-binding hemagglutinin, a virulence factor of Mycobacterium tuberculosis, was found to bind at least six sugar units with the interaction notably being entropically driven.
Desymmetrization of 2,4,5,6-Tetra-O-benzyl-D-myo-inositol for the Synthesis of Mycothiol
(2011-10-21)
Chung, Chuan-Chung
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Zulueta, Medel Manuel L.
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Padiyar, Laxmansingh T.
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Hung, Shang-Cheng
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應用化學系
An efficient chemical synthesis of mycothiol Involving the regioselective ketopinyl desymmetrization of 2,4,5,6-tetrabenzylated D-myo-inositol as the key step Is described. Together with a highly alpha-stereoselective D-glucosaminylation, the whole procedure was accomplished in eight steps with an overall yield of 40%.
Deuterium-isotope study on the reductive ring opening of benzylidene acetals
(2011)
Lee, I-Chi
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Zulueta, Medel Manuel L.
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Shie, Chi-Rung
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Arco, Susan D.
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Hung, Shang-Cheng
Specific deuterated reference compounds were prepared to probe the stereoselectivity of the reductive ring opening of carbohydrate-based benzylidene-type acetals. AlD(3) revealed a retentive stereoselectivity probably through the rare S(N)i (internal nucleophilic substitution) mechanism. An S(N)1-like mechanism occurs in the acid-promoted regioselective BD(3)center dot THF- or Et(3)SiD-reductive ring opening.
Divergent Synthesis of 48 Heparan Sulfate-Based Disaccharides and Probing the Specific Sugar-Fibroblast Growth Factor-1 Interaction
(2012-12-26)
Hu, Yu-Peng
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Zhong, Yong-Qing
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Chen, Zhi-Geng
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Chen, Chun-Yen
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Shi, Zhonghao
Several biological processes involve glycans, yet understanding their ligand specificities is impeded by their inherent diversity and difficult acquisition. Generating broad synthetic sugar libraries for bioevaluations is a powerful tool in unraveling glycan structural information. In the case of the widely distributed heparan sulfate (HS), however, the 48 theoretical possibilities for its repeating disaccharide call for synthetic approaches that should minimize the effort in an undoubtedly huge undertaking. Here we employed a divergent strategy to afford all 48 HS-based disaccharides from just two orthogonally protected disaccharide precursors. Different combinations and sequence of transformation steps were applied with many downstream intermediates leading up to multiple target products. With the full disaccharide library in hand, affinity screening with fibroblast growth factor-1 (FGF-1) revealed that four of the synthetic sugars bind to FGF-1. The molecular details of the interaction were further clarified through X-ray analysis of the sugar-protein cocrystals. The capability of comprehensive sugar libraries in providing key insights in glycan-ligand interaction is, thus, highlighted.
One-Pot Strategies for the Synthesis of the Tetrasaccharide Linkage Region of Proteoglycans
(2011-03-18)
Huang, Teng-Yi
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Zulueta, Medel Manuel L.
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Hung, Shang-Cheng
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應用化學系
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Department of Applied Chemistry
A linker-attached tetrasaccharide corresponding to the linkage region of proteoglycans was synthesized via one-pot procedures from the silylated monosaccharide derivatives. Regioselective one-pot protection protocols were applied in generating the requisite monosaccharide building blocks whereas stereoselective one-pot glycosylation approaches were utilized to assemble the tetrasaccharide skeleton.
Regioselective and stereoselective benzylidene installation and one-pot protection of D-mannose
(2013)
Patil, Pratap S.
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Lee, Chia-Chen
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Huang, Yu-Wen
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Zulueta, Medel Manuel L.
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Hung, Shang-Cheng
Oligosaccharide syntheses are an important source of well-defined sugar constructs particularly needed for the evaluation of structure-activity relationships. The chemical assembly of oligosaccharides requires several building blocks, that is, glycosyl donors and acceptors, which are prepared in multistep processes and in a generally tedious and time-consuming manner. Having developed one-pot procedures meant to minimise the effort in sugar building block preparation, we tackled herein the one-pot preparation of fully protected and 2-, 3-, 4-, and 6-alcohol derivatives of D-mannose, a widely distributed monosaccharide. As a consequence of the hydroxyl group pattern of D-mannose, regioselective and stereoselective benzylide-nations were developed and later seamlessly utilised as the first transformation in the one-pot procedure.
Regioselective One-Pot Protection of D-Glucosamine
(2010-11-05)
Chang, Ken-Lien
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Zulueta, Medel Manuel L.
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Lu, Xin-An
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Zhong, Yong-Qing
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Hung, Shang-Cheng
A highly regioselective one-pot transformation of 2-azido2-deoxy-1,3,4,6-tetra-O-trimethylsilyl-D-glucopyranose via sequential additions of various reagents was systematically studied, yielding the fully protected derivatives and the 1-, 3-, 4-, as well as 6-alcohols, respectively.
Single-Step Per-O-Sulfonation of Sugar Oligomers with Concomitant 1,6-Anhydro Bridge Formation for Binding Fibroblast Growth Factors
(2019-01-18)
Yeh, Che-Jui
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Ku, Chiao-Chu
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Lin, Wei-Chen
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Fan, Chiao-Yuan
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Zulueta, Medel Manuel L.
Many circulating cancer-related proteins, such as fibroblast growth factors (FGFs), associate with glycosaminoglycans-particularly heparan sulfate-at the cell surface. Disaccharide analogues of heparan sulfate had previously been identified as the shortest components out of the sugars that bind to FGF-1 and FGF-2. Taking note of the typical pose of l-iduronic acid, we conceived of per-O-sulfonated analogues of such disaccharides, and devised a single-step procedure for per-O-sulfonation of unprotected sugars with concomitant 1,6-anhydro bridge formation to achieve such compounds through direct use of SO3Et3N as sulfonation reagent and dimethylformamide as solvent. The synthesized sugars based on the oligomaltose backbone bound FGF-1 and FGF-2 mostly at the sub-micromolar level, although the tetrasaccharide analogue achieved low-nanomolar binding with FGF-2.
Synthesis of 3-O-sulfonated heparan sulfate octasaccharides that inhibit the herpes simplex virus type 1 host-cell interaction
(2011-07-01)
Hu, Yu-Peng
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Lin, Shu-Yi
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Huang, Cheng-Yen
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Zulueta, Medel Manuel L.
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Liu, Jing-Yuan
Cell surface carbohydrates play significant roles in a number of biologically important processes. Heparan sulfate, for instance, is a ubiquitously distributed polysulfated polysaccharide that is involved, among other things, in the initial step of herpes simplex virus type 1 (HSV-1) infection. The virus interacts with cell-surface heparan sulfate to facilitate host-cell attachment and entry. 3-O-Sulfonated heparan sulfate has been found to function as an HSV-1 entry receptor. Achieving a complete understanding of these interactions requires the chemical synthesis of such oligosaccharides, but this remains challenging. Here, we present a convenient approach for the synthesis of two irregular 3-O-sulfonated heparan sulfate octasaccharides, making use of a key disaccharide intermediate to acquire different building blocks for the oligosaccharide chain assembly. Despite substantial structural differences, the prepared 3-O-sulfonated sugars blocked viral infection in a dosage-dependent manner with remarkable similarity to one another.
Synthesis of a fluorogenic substrate for alpha-L-iduronidase
(2013)
Lu, Fu-Chieh
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Lico, Larry S.
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Hung, Shang-Cheng
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應用化學系
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Department of Applied Chemistry
An alternative reaction pathway towards the preparation of an L-idopyranose derivative and its application to the synthesis of the alpha-L-iduronidase fluorogenic substrate 4-methylcoumarin-7-yl-alpha-L-iduronic acid as well as its 3-undecyl derivative are described. The L-ido sugar was prepared by converting the commercially available diacetone-alpha-D-glucose to methyl 1,2,3,4-tetra-O-acetyl-L-idopyranuronate via oxidation, esterification, and regioselective acetylation of the key intermediate 1,2:3,5-di-O-isopropylidene-beta-L-idofuranose. Mitsunobu-type glycosylation was employed in the coupling of the L-ido donor with the 4-methylcoumarin acceptors. This newly developed route reduced the difficulties previously encountered in the synthesis of the alpha-L-iduronidase fluorogenic substrate.
Synthesis of a Furanosyl-pyranone Derivative Related to the Tri-O-heterocyclic Core of Herbicidins
(2012-03-01)
Hsu, Ching-Yun
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Lee, I-Chi
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Lico, Larry S.
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Uang, Biing-Jiun
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Hung, Shang-Cheng
A new compound that is structurally related to the undecose ring structure of herbicidins has been prepared. The synthesis of this novel furanosyl-pyranone derivative was made possible through the regioselective reductive ring-opening of a 3,5-O-benzylidene-D-xylofuranose and the hetero-Diels-Alder reaction of an aldehyde and a Danishefsky-type diene. The highly functionalized pyranone derivative can be a useful precursor for the synthesis of herbicidins.
Synthesis of heparin oligosaccharides and their interaction with eosinophil-derived neurotoxin
(2012)
Hung, Shang-Cheng
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Lu, Xin-An
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Lee, Jinq-Chyi
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Chang, Margaret Dah-Tsyr
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Fang, Shun-lung
A convenient route for the synthesis of heparin oligosaccharides involving regioselective protection of D-glucosamine and a concise preparation of rare L-ido sugars from diacetone alpha-D-glucose is described. Stereoselective coupling of a D-glucosamine-derived trichloroacetimidate with a 1,6-anhydro-beta-L-idopyranosyl 4-alcohol gave the desired a-linked disaccharide, which was used as repeating unit for dual chain elongation and termination. Stepwise assembly from the reducing to the non-reducing end with a D-glucosamine-derived monosaccharide as starting unit furnished the oligosaccharide skeletons having different chain lengths. A series of functional group transformations afforded the expected heparin oligosaccharides with 3, 5 and 7 sugar units. Interaction of these oligosaccharides with eosinophil-derived neurotoxin (EDN), a cationic ribonuclease and a mediator produced by human eosinophils, was further investigated. The results revealed that at 5 mu g mL(-1), the heptasaccharide has sufficiently strong interference to block EDN binding to Beas-2B cells. The tri- and pentasaccharides have moderate inhibitory properties at 50 mu g mL(-1) concentration, but no inhibition has been observed at 10 mu g mL(-1). The IC(50) values of the tri-, penta- and heptasaccharides are 69.4, 47.2 and 0.225 mu g mL(-1), respectively.
Synthesis of hyaluronic acid oligosaccharides with a GlcNAc-GlcA repeating pattern and their binding affinity with CD44
(2020-07-28)
Yeh, Che-Jui
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Zulueta, Medel Manuel L.
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Li, Yaw-Kuen
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Hung, Shang-Cheng
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應用化學系
Hyaluronic acid (HA) is a ubiquitous glycosaminoglycan in the extracellular matrix and a ligand of CD44, a transmembrane glycoprotein that is important in cell migration. Crystal and NMR studies found a hexasaccharide of the pattern (GlcA-GlcNAc)(3)as the shortest HA that could bind to CD44, but molecular dynamics simulations indicated that a tetrasaccharide of the pattern (GlcNAc-GlcA)(2)is the key structure interacting with CD44. Access to oligomers with such a repeat pattern is crucial in binding studies with CD44. Here we developed a synthetic procedure to afford the HA oligosaccharides with the GlcNAc-GlcA repeating unit and measured the binding interaction between these sugars and human CD44 by isothermal titration calorimetry (ITC). During the chemical synthesis, we successfully generated the beta-glycosidic bond in the absence of neighbouring group participation and overcome the issues in the oxidation step. In addition, ammonia-free dissolving metal reduction for debenzylation and azido reduction has been applied in carbohydrate synthesis for the first time. ITC analysis revealed that the HA tetrasaccharide (GlcNAc-GlcA)(2)could indeed interact and bind to the human CD44.
Synthesis of L-hexoses and their related biomolecules
(2013)
Zulueta, Medel Manuel L.
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Zhong, Yong-Qing
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Hung, Shang-Cheng
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應用化學系
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Department of Applied Chemistry
Carbohydrates either conjugated or as free entities are major players in numerous biological processes. The desire to comprehend the nature of their functions and further develop therapeutic and diagnostic applications has fuelled the recent upsurge in the glycoscience field. Mainly accessed through chemical synthesis, homogeneous and well-defined sugar constructs are on high demand for structure-activity evaluation. Although the D-sugars, particularly the D-hexoses, have dominated the carbohydrate landscape, L-hexoses also attracted attention because they are known components of important polysaccharides, antibiotics, and other natural products. Nonetheless, the L-hexose-based materials needed for making building blocks for sugar assemblies are rare and are usually expensive if commercially available. Thus, intense efforts were focused on the development of innovative and reliable methods for the acquisition of L-hexoses and their derivatives. This review outlines several efficient and cost-effective routes for the chemical syntheses of L-hexoses, particularly focusing on approaches that utilize commercially abundant sugars as starting materials. A sampling of the applications of the generated L-hexoses in preparing biologically relevant compounds is also provided.
Synthetic heparin and heparan sulfate oligosaccharides and their protein interactions
(2013-12-01)
Zulueta, Medel Manuel L.
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Lin, Shu-Yi
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Hu, Yu-Peng
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Hung, Shang-Cheng
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應用化學系
Heparin and heparan sulfate bind a host of basic proteins that take advantage of the sugar's dense structural information. The significance of these interactions in various aspects of development, physiology, and disease stimulated keen interest in evaluating structure-activity relationships. The well-defined heparin and heparan sulfate oligosaccharides needed for these studies can be mainly accessed by chemical synthesis and, more recently by chemoenzymatic means. The various synthetic strategies available to chemical synthesis have recently enabled the acquisition of several regular and irregular sequences, including a number of dodecasaccharides, through improved coupling methods and judicial protecting group manipulations. Controlled chain elongation and critical application of modification enzymes allowed the generation of well-defined constructs via chemoenzymatie synthesis. Investigations of various protein interactions with the synthetic constructs delivered valuable information that could aid future drug development endeavors.