Browsing by Author "Wang, Cheng-Chung"

Now showing 1 - 3 of 3

Concise synthesis of 2,7-anhydrosialic acid derivatives and its application
(2017-12-14)
Asressu, Kesatebrhan Haile
;
Wang, Cheng-Chung
;
應用化學系
;
Department of Applied Chemistry
In N-acetylneuraminic acid, apart from O9 and O8, a possible glycosylation site is the O4 position. For example, gangliosides HLG-2 and HPG-7 are considered to be potential lead compounds for carbohydrate-based drug development to treat neural disorders. However, the construction of their alpha(1 -> 4) fucosyl sialic acid and alpha(2 -> 4) linkages between sialic acids is difficult because of the regioselectivity problem. Herein, N-acetyl-2,7-anhydroneuraminic acid was synthesized in three steps from Neu5Ac methyl ester through per-O-trimethylsilylation, heating-assisted intramolecular anomeric protection (iMAP) and desilylation. The iMAP simultaneously circumvents both the 2- and 7-OH protection. Upon protecting the 8- and 9-OH groups as a benzylidene acetal, only 4-OH is free for glycosylation. These 2,7-anhydro-8,9-O-benzylidenesialic acid derivatives were examined as acceptor for an alpha-selective fucosylation to construct the glycosidic linkage of fucosyl alpha(1 -> 4) 2,7-anhydroneuraminic acid. (C) 2017 Published by Elsevier Ltd.
Divergent Synthesis of 48 Heparan Sulfate-Based Disaccharides and Probing the Specific Sugar-Fibroblast Growth Factor-1 Interaction
(2012-12-26)
Hu, Yu-Peng
;
Zhong, Yong-Qing
;
Chen, Zhi-Geng
;
Chen, Chun-Yen
;
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.
SnCl4-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives
(2019-12-23)
Asressu, Kesatebrhan Haile
;
Wang, Cheng-Chung
;
應用化學系
;
Department of Applied Chemistry
Sialic acid-containing glycans are found in different sialic acid forms and a variety of glycosidic linkages in biologically active glycoconjugates. Hence, the preparation of suitably protected sialyl building blocks requires high attention in order to access glycans in a pure form. In line with this, various C-5-substituted 2,7-anhydrosialic acid derivatives bearing both electron-donating and -withdrawing protecting groups were synthesized and subjected to different Lewis acid-catalyzed solvent-free ring-opening reactions at room temperature in the presence of acetic anhydride. Among the various Lewis acids tested, the desired acetolysis products were obtained in moderate yields under tin(IV) chloride catalysis. Our methodology could be extended to regioselective protecting group installations and manipulations towards a number of thiosialoside and halide donors.