Browsing by Author "Mong, Kwok-Kong Tony"

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(2-Ketulosonyl)onate 2,3-O-thionocarbonate donors for the synthesis of KO and KDO alpha-glycosides and a one-pot glycosylation method for 2-keto acid donors
(2020-08-21)
Mong, Kwok-Kong Tony
;
Pradhan, Tapan Kumar
;
Chiu, Cheng-Hsin
;
Hung, Wei-Cheng
;
Chen, Chao-Ju
We report a short synthetic strategy for direct preparation of (2-ketulosonyl)onate donors. These donors feature a cyclic thionocarbonate group at the C2 and C3 positions, which plays a multitude of chemical roles. It protects the C2 and C3 hydroxyls during building block preparation. In glycosylation, the thionocarbonate can be activated by a sulfenylating promoter and serves as a leaving group. Because of its beta-configuration, it also plays the role of a stereo-directing group during the formation of the alpha-glycosidic bond. In addition, the thionocarbonate donors can couple with thioglycoside acceptors. This orthogonal property was used for the development of the first one-pot glycosylation method for 2-keto acid sugars.
A concise synthesis of single components of partially sulfated oligomannans
(2015-01-01)
Mong, Kwok-Kong Tony
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Shiau, Kai-Sheng
;
Lin, Yu Hsien
;
Cheng, Kuang-Chun
;
Lin, Chun-Hung
A concise synthesis of single components of C2 sulfated oligomannans including trimers, tetramers, and pentamers is reported. The synthesis features the application of the DMF-modulation method for the participatory thiomannoside donors in 1,2-trans alpha-glycosidic bond formation. The obtained oligomannans were fully characterized using H-1, C-13, COSY, and HSQC NMR spectroscopy.
A flexible 1,2-cis alpha-glycosylation strategy based on in situ adduct transformation
(2017-07-07)
Hu, Jhe-Cyuan
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Feng, Ai-Fen Wendy
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Chang, Bo-Yao
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Lin, Chun-Hung
;
Mong, Kwok-Kong Tony
A flexible 1,2-cis alpha-selective glycosylation strategy for a wide range of glycosyl donors and acceptors has been developed, which is based on an in situ adduct transformation protocol. Based on this strategy, both NFM-derived and iodide covalent adducts can be accessed for glycosylation. Using low temperature NMR spectroscopy, the aforementioned glycosyl adducts were detected.
A general strategy for diverse syntheses of anhydrolandomycinone, tetrangulol, and landomycinone
(2018-02-21)
Sie, Cheng-Jhe
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Patteti, Venukumar
;
Yang, Yi-Ru
;
Mong, Kwok-Kong Tony
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應用化學系
A general synthetic strategy based on a protecting group-promoted CH arylation method was developed for total syntheses of anhydro-landomycinone (1), tetrangulol (2), and landomycinone (3) from the same set of starting materials.
A general synthetic strategy and the anti-proliferation properties on prostate cancer cell lines for natural phenylethanoid glycosides
(2014-01-01)
Mulani, Shaheen K.
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Guh, Jih-Hwa
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Mong, Kwok-Kong Tony
;
應用化學系
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Department of Applied Chemistry
A general strategy for the synthesis of phenylethanoid glycosides (PhG) including echinacoside 1, acteoside 2, calceolarioside-A 3 and calceolarioside-B 4 is reported. The strategy features the application of low substrate concentration glycosylation and N-formyl morpholine modulated glycosylation methods for the construction of 1,2-trans beta- and alpha-glycosidic bonds. The reported strategy does not invoke the use of the participatory acyl protecting function, which is incompatible with the ester function present in target PhG compounds. A preliminary study of the anti-proliferation properties of the PhG compounds 1-4 was performed; the acteoside 2 exhibited the best inhibition on the prostatic cancer cell proliferation.
A general synthetic strategy and the anti-proliferation properties on prostate cancer cell lines for natural phenylethanoid glycosides
(2014-01-01)
Mulani, Shaheen K.
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Guh, Jih-Hwa
;
Mong, Kwok-Kong Tony
;
交大名義發表
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National Chiao Tung University
A general strategy for the synthesis of phenylethanoid glycosides (PhG) including echinacoside 1, acteoside 2, calceolarioside-A 3 and calceolarioside-B 4 is reported. The strategy features the application of low substrate concentration glycosylation and N-formyl morpholine modulated glycosylation methods for the construction of 1,2-trans beta- and alpha-glycosidic bonds. The reported strategy does not invoke the use of the participatory acyl protecting function, which is incompatible with the ester function present in target PhG compounds. A preliminary study of the anti-proliferation properties of the PhG compounds 1-4 was performed; the acteoside 2 exhibited the best inhibition on the prostatic cancer cell proliferation.
A straightforward alpha-selective aromatic glycosylation and its application for stereospecific synthesis of 4-methylumbelliferyl alpha-T-antigen
(2009-03-10)
Chang, Shih-Sheng
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Lin, Chun-Cheng
;
Li, Yaw-Kuen
;
Mong, Kwok-Kong Tony
;
應用化學系
A practical and efficient alpha-selective aromatic glycosylation with simple per-O-acetyl glycopyranosyl trichloroacetimidates is reported. The method is particularly effective for L-fucosyl and 2-azido-2-deoxy-D-galatosaminyl imidates, with which exclusive alpha-selectivity was achieved. The synthetic utility of this method was demonstrated in the stereoselective synthesis of 4-methylumbelliferyl alpha-T-antigen. (C) 2008 Elsevier Ltd. All rights reserved.
Application of 2-Azido-2-deoxythioglycosides for beta-Glycoside Formation and Oligosaccharide Synthesis
(2012-05-01)
Mong, Kwok-Kong Tony
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Yen, Yu-Fang
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Hung, Wei-Cheng
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Lai, Yen-Hsun
;
Chen, Jiun-Han
Most natural 2-acetamido-2-deoxyglycosides exist in a 1,2-trans-beta-glycosidic configuration. This study investigated the use of 2-azido-2-deoxythioglycosides for 1,2-trans-beta-glycosidic bond formation under low-concentration glycosylation conditions. Further application of the 2-azido-2-deoxythioglycosyl substrates for one-pot oligosaccharide synthesis was demonstrated in the synthesis of protected beta-(1?6)-N-acetylglucosamine trimer, core-6serine conjugate, and F1a serine conjugate.
Automated Solution-Phase Synthesis of Oligosaccharides via Iterative Electrochemical Assembly of Thioglycosides
(2013-09-06)
Nokami, Toshiki
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Hayashi, Ryutaro
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Saigusa, Yoshihiro
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Shimizu, Akihiro
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Liu, Chih-Yueh
A new iterative one-pot sequential method for the solution-phase synthesis of oligosaccharides has been devised on the basis of the electrochemical oxidation of a propagating thioglycoside terminus to generate the corresponding triflate, followed by the reaction with a thioglycoside building block having a free hydroxyl group. A practical automated synthesizer was developed for the method and was effectively used for assembling up to six thioglycoside building blocks to synthesize partial structures of poly-beta-D-(1-6)-N-acetylglucosamine.
C6 picoloyl protection: a remote stereodirecting group for 2-deoxy-beta-glycoside formation
(2015-01-01)
Ruei, Jyh-Herng
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Venukumar, Patteti
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Ingle, Arun B.
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Mong, Kwok-Kong Tony
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應用化學系
We reported a remote control glycosylation method using the picoloyl protecting group for 2-deoxy-beta-glycosidic bond formation. The method is applicable to various 2-deoxythioglycosyl donors and the utility is illustrated by the synthesis of a deoxytrisaccharide component of landomycins.
Chemical Glycosylation by Single Electron Transfer
(2015-04-01)
Nokami, Toshiki
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Itoh, Toshiyuki
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Mong, Kwok-Kong Tony
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應用化學系
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Department of Applied Chemistry
Oligosaccharides play important roles in nature; however, chemical synthesis of oligosaccharides is still difficult and not carried out in a fully automated manner. Among various methods, the activation of glycosyl donors by single electron transfer using electrochemical and photochemical methods has several benefits. In particular, electrochemical oxidation is a powerful method to activate glycosyl donors, including thioglycosides, which are one of the most popular class of glycosyl donors in modern chemical glycosylations. This review article covers the pioneering works of electrochemical glycosylations, other chemical glycosylations achieved by single electron transfer, and our recent approach to the automated solution-phase synthesis of oligosaccharides based on the electrochemical method.
Chemical Synthesis of the O-Antigen Repeating Unit of Escherichia coli O86 by an N-Formylmorpholine-Modulated One-Pot Glycosylation Strategy
(2014-08-01)
Ingle, Arun B.
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Chao, Chin-Sheng
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Hung, Wei-Cheng
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Mong, Kwok-Kong Tony
;
應用化學系
The synthesis of the O-antigen pentasaccharide repeating unit of the cell wall of Gram-negative bacteria Escherichia coli O86 is reported. The synthesis features the use of an N-formylmorpholine (NFM)-modulated glycosylation method for the construction of 1,2-cis alpha-glycosidic linkages and an [1+1+2] iterative one-pot alpha-glycosylation strategy to accelerate the assembly of the tetrasaccharide backbone.
Cholesteryl alpha-D-glucoside 6-acyltransferase enhances the adhesion of Helicobacter pylori to gastric epithelium
(2020-03-13)
Jan, Hau-Ming
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Chen, Yi-Chi
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Yang, Tsai-Chen
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Ong, Lih-Lih
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Chang, Chia-Chen
Helicobacter pylori, the most common etiologic agent of gastric diseases including gastric cancer, is auxotrophic for cholesterol and has to hijack it from gastric epithelia. Upon uptake, the bacteria convert cholesterol to cholesteryl 6 '-O-acyl-alpha-D-glucopyranoside (CAG) to promote lipid raft clustering in the host cell membranes. However, how CAG appears in the host to exert the pathogenesis still remains ambiguous. Herein we identified hp0499 to be the gene of cholesteryl alpha-D-glucopyranoside acyltransferase (CGAT). Together with cholesteryl glucosyltransferase (catalyzing the prior step), CGAT is secreted via outer membrane vesicles to the host cells for direct synthesis of CAG. This significantly enhances lipid rafts clustering, gathers adhesion molecules (including Lewis antigens and integrins alpha 5, beta 1), and promotes more bacterial adhesion. Furthermore, the clinically used drug amiodarone was shown as a potent inhibitor of CGAT to effectively reduce the bacterial adhesion, indicating that CGAT is a potential target of therapeutic intervention. Jan et al. identify cholesteryl alpha-D- glucopyranoside acyltransferase as a key enzyme in Helicobacter pylori's synthesis of cholesteryl 6'-O-acyl-alpha-D-glucopyranoside, which promotes bacterial adhesion. This study provides insights into the H. pylori-induced pathogenesis and therapeutic strategies against it.
Development of a novel engineered antibody targeting Neisseria species
(2017-03)
Liu, Chih-Yueh
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Weng, Chang-Ching
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Lin, Chih-Hsiang
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Yang, Chiou-Ying
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Mong, Kwok-Kong Tony
A Neissaria bacterial pilus sugar, bacillosamine, was synthesized and, for the first time, used as a probe to screen a single-chain variable fragment (scFv). Four Neisseria, Neisseria gonorrhoeae, Neisseria meningitidis, Neisseria sicca and Neisseria subflava, and two negative controls, Streptococcus pneumoniae and Escherichia coli, were tested through ELISA, immunostaining and gold nanoparticle immunological assay. All results indicated that the selected scFv is feasible for the specific detection of Neisseria species via the recognition of bacillosamine. The recombinant scFv could detect Neisseria strains at 10(6) CFU/ml.
Dimethylformamide: An Unusual Glycosylation Modulator
(2011)
Lu, Shao-Ru
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Lai, Yen-Hsun
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Chen, Jiun-Han
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Liu, Chih-Yueh
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Mong, Kwok-Kong Tony
Diverse Synthesis of Natural Trehalosamines and Synthetic 1,1 '-Disaccharide Aminoglycosides
(2019-01-18)
Lu, Yen-Chu
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Mondal, Soumik
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Wang, Ching-Chi
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Lin, Chun-Hung
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Mong, Kwok-Kong Tony
A general strategy for the diverse synthesis of ten disaccharide aminoglycosides, including natural 2-trehalosamine (1), 3-trehalosamine (2), 4-trehalosamine (3), and neotrehalosyl 3,3 '-diamine (8) and synthetic aminoglycosides 4-7, 9, and 10, has been developed. The aminoglycoside compounds feature different anomeric configurations and numbers of amino groups. The key step for the synthesis was the glycosylation coupling of a stereodirecting donor with a configuration-stable TMS glycoside acceptor. Either the donor or acceptor could be substituted with an azido group. The aminoglycosides prepared in the present study were characterized by 1D and 2D NMR spectroscopy.
Identification of Essential Residues of Human alpha-L-Fucosidase and Tests of Its Mechanism
(2009-01-13)
Liu, Sheng-Wen
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Chen, Chao-Sheng
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Chang, Shih-Shen
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Mong, Kwok-Kong Tony
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Lin, Chun-Hung
Fucosylated glycoconjugates have critical roles in biological processes, but a limited availability Of alpha-L-fucosidase has hampered research on this human enzyme (h-Fuc) at a molecular level. After overexpressing h-Fuc in Escherichia coli as an active form, we investigated the catalytic function of this recombinant enzyme. Based on sequence alignment and structural analysis of close homologues of h-Fuc, nine residues of glutamate and aspartate in h-Fuc were selected for mutagenic tests to determine the essential residues. Among the mutants, D225N, E289Q, and E289G lost catalytic activity significantly; their k(cat) values are 1/5700, 1/430, and 1/340, respectively, of that of the wild-type enzyme. The Bronsted plot for k(cat)/K(m) for the E289G mutant is linear with beta(1g) = -0.93, but that for k(cat) is biphasic, with beta(1g) for poor substrates being -0.88 and for activated substrates being -0.11. The small magnitude of Pig for the activated substrates may indicate that the rate-limiting step of the reaction is defucosylation, whereas the large magnitude of the latter Pig value for the poor substrates indicates that the rate-limiting step of the reaction becomes fucosylation. The kinetic outcomes support an argument that ASp(225) functions as a nucleophile and Glu(289) as a general acid/base catalyst. As further evidence, azide significantly reactivated D225G and E289G, and (1)H NMR spectral analysis confirmed the formation of beta-fucosyl azide and alpha-fucosyl azide in the azide rescues of D225G and E289G catalyses, respectively. As direct evidence to prove the function of Glu(289), an accumulation of fucosyl-enzyme intermediate was detected directly through ESI/MS analysis.
Identification of Pseudomonas aeruginosa using functional magnetic nanoparticle-based affinity capture combined with MALDI MS analysis
(2009)
Liu, Jr-Chi
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Chen, Wei-Jen
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Li, Chen-Wei
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Mong, Kwok-Kong Tony
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Tsai, Pei-Jane
PA-IL is a galactophilic lectin that is found on the outer membrane of Pseudomonas aeruginosa. Pigeon ovalbumin (POA), a phosphoprotein, contains high levels of terminal Gala(1 -> 4) Gal units. Thus, magnetic nanoparticles with immobilized POA can be used as affinity probes for P. aeruginosa, functioning via the recognition of galactophilic PA-IL. We fabricated POA-bound nanoparticles (NPs) by immobilizing POA onto the surface of core/shell magnetic iron oxide/alumina NPs via metal phosphate chelation. We then used the generated NPs to probe target bacteria from complex samples. The trapped bacterial cells were characterized based on their mass peak profiles obtained from MALDI MS analyses. In addition, we confirmed the determination of P. aeruginosa using a proteomic strategy: combining the resultant MALDI MS/MS spectra of its tryptic digest with protein database searching. The feasibility of using this approach to rapidly characterize P. aeruginosa from clinical samples without the need to perform culturing steps was also demonstrated.
In situ formation of beta-glycosyl imidinium triflate from participating thioglycosyl donors: elaboration to disarmed-armed iterative glycosylation
(2012)
Lin, Yu Hsien
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Ghosh, Bhaswati
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Mong, Kwok-Kong Tony
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應用化學系
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Department of Applied Chemistry
beta-Glycosyl imidinium triflate is generated from participating thioglycoside donors for disarmed-armed iterative glycosylations and one-pot oligosaccharide synthesis.
Iterative alpha-Glycosylation Strategy for 2-Deoxy- and 2,6-Dideoxysugars: Application to the One-Pot Synthesis of Deoxysugar-Containing Oligosaccharides
(2014-03-01)
Chen, Jiun-Han
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Ruei, Jyh-Herng
;
Mong, Kwok-Kong Tony
;
應用化學系
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Department of Applied Chemistry
This paper describes the development of an iterative and -selective glycosylation method for 2-deoxyglycosyl and 2,6-dideoxythioglycoside donors based on the DMF modulation concept. We used NMR spectroscopy to probe the 2-deoxyglycosyl imidinium intermediate and elucidated the conditions to decrease the formation of glycal and thus to increase the reaction yields. Further elaboration of the glycosylation method opened the gate for an iterative one-pot synthesis of 2-deoxy- and 2,6-dideoxyglycoside-containing oligosaccharides.