144 results on '"Xin, Shan"'
Search Results
2. Synthesis and Immunological Evaluation of Pentamannose-Based HIV-1 Vaccine Candidates
- Author
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Chang-Cheng Liu, Chang-Xin Huo, Canjia Zhai, Xiu-Jing Zheng, De-Cai Xiong, and Xin-Shan Ye
- Subjects
Pharmacology ,Vaccines ,Organic Chemistry ,Biomedical Engineering ,Pharmaceutical Science ,Bioengineering ,HIV Antibodies ,HIV Envelope Protein gp120 ,Antibodies, Neutralizing ,Epitopes ,Mice ,Polysaccharides ,HIV-1 ,Animals ,Humans ,Glycoconjugates ,Biotechnology - Abstract
Dense glycosylation and the trimeric conformation of the human immunodeficiency virus-1 (HIV-1) envelope protein limit the accessibility of some cellular glycan processing enzymes and end up with high-mannose-type
- Published
- 2022
3. Additive-controlled synthesis of 1- and 2-deoxysugars from thioglycosides
- Author
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Xia Wu, Biao Wu, Chen-Fei Gao, Xin-Shan Ye, and De-Cai Xiong
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Organic Chemistry ,Biochemistry - Published
- 2021
4. Plasma Treatments and Light Extraction from Fluorinated CVD-Grown (400) Single Crystal Diamond Nanopillars
- Author
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Mariusz Radtke, Abdallah Slablab, Sandra Van Vlierberghe, Chao-Nan Lin, Ying-Jie Lu, and Chong-Xin Shan
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single crystal diamond ,nitrogen vacancies ,nanofabrication ,Organic chemistry ,QD241-441 - Abstract
We investigate the possibilities to realize light extraction from single crystal diamond (SCD) nanopillars. This was achieved by dedicated 519 nm laser-induced spin-state initiation of negatively charged nitrogen vacancies (NV−). We focus on the naturally-generated by chemical vapor deposition (CVD) growth of NV−. Applied diamond was neither implanted with 14N+, nor was the CVD synthesized SCD annealed. To investigate the possibility of light extraction by the utilization of NV−’s bright photoluminescence at room temperature and ambient conditions with the waveguiding effect, we have performed a top-down nanofabrication of SCD by electron beam lithography (EBL) and dry inductively-coupled plasma/reactive ion etching (ICP-RIE) to generate light focusing nanopillars. In addition, we have fluorinated the diamond’s surface by dedicated 0 V SF6 ICP plasma. Light extraction and spin manipulations were performed with photoluminescence (PL) spectroscopy and optically detected magnetic resonance (ODMR) at room temperature. We have observed a remarkable effect based on the selective 0 V SF6 plasma etching and surprisingly, in contrast to literature findings, deactivation of NV− centers. We discuss the possible deactivation mechanism in detail.
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- 2020
- Full Text
- View/download PDF
5. Synthesis and immunological evaluation of N-acyl modified Globo H derivatives as anticancer vaccine candidates
- Author
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Chengcheng Song, Xiu-Jing Zheng, Xin-Shan Ye, and Canjia Zhai
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Synthetic vaccine ,Glycosylation ,Glycoconjugate ,medicine.medical_treatment ,Pharmaceutical Science ,H antigen ,010402 general chemistry ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Immune system ,Drug Discovery ,medicine ,Pharmacology ,chemistry.chemical_classification ,biology ,010405 organic chemistry ,Immunogenicity ,Organic Chemistry ,0104 chemical sciences ,chemistry ,Cancer research ,biology.protein ,Molecular Medicine ,Antibody ,Adjuvant - Abstract
Globo H is a tumor-associated carbohydrate antigen (TACA), which serves as a valuable target for antitumor vaccine or cancer immunotherapies. However, most TACAs are T-cell-independent, and they cannot induce powerful immune response due to their poor immunogenicity. To address this problem, herein, several Globo H analogues with modification on the N-acyl group were prepared through a preactivation-based glycosylation strategy from the non-reducing end to the reducing end. These modified Globo H derivatives were then conjugated with carrier protein CRM197 to form glycoconjugates as anticancer vaccine candidates, which were used in combination with adjuvant glycolipid C34 for immunological studies. The immunological effects of these synthetic vaccine candidates were evaluated on Balb/c mice. The results showed that the fluorine-modified N-acyl Globo H conjugates can induce higher titers of IgG antibodies that can recognize the naturally occurring Globo H antigen on the surface of cancer cells and can eliminate cancer cells in the presence of a complement, indicating the potential of these synthetic glycoconjugates as anticancer vaccine candidates.
- Published
- 2021
6. Anti-Depressive Effectiveness of Baicalin In Vitro and In Vivo
- Author
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Li Liu, Yu Dong, Xin Shan, Lin Li, Baomei Xia, and Hanqing Wang
- Subjects
baicalin ,antidepressant ,chronic unpredictable mild stress ,inflammation ,HMGB1/TLR4/NF-κB ,Organic chemistry ,QD241-441 - Abstract
Baicalin (BA), a major polyphenol compound isolated from the extracts of Scutellaria radix, has been previously reported to ameliorate depressive-like behaviors in mice with chronic unpredictable mild stress (CUMS). However, its underlying antidepressant mechanisms remain unclear. This study was designed to confirm the antidepressant-like effects of BA on CUMS induced behavioral abnormalities in mice, and sought to explore the pharmacological mechanisms in vivo and in vitro. The CUMS procedure was carried out to induce depression in mice. Afterwards, the tail suspension test (TST), forced swim test (FST), and open field test (OFT) were performed within 24 h, then sucrose preference test (SPT) was conducted. Additionally, PC12 cells were pretreated with BA for 2 h, then further stimulated with corticosterone for 24 h. The levels of Interleukin-1β (IL-1β), IL-6 and Tumor Necrosis Factor-α (TNF-α) in serum, hippocampus homogenate and cell culture medium were determined using the enzyme-linked immunosorbent assay (ELISA) method. The protein expressions of inhibition of high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathways in hippocampus and PC12 cells were detected. Our results showed that CUMS-treated mice presented notable depressive-like symptoms, such as decreased sucrose consumption, increased FST and TST immobility time. While BA (25, 50 mg/kg) significantly attenuated these changes. Besides, BA treatment considerably inhibited inflammatory cytokinesl (IL-1β, IL-6, TNF-α) levels in serum, hippocampus homogenate and cell culture medium. Western blot analysis indicated that BA inhibited the expressions of HMGB1, TLR4, and p-NF-κBp65 both in vivo and in vitro. In conclusion, the present study confirmed that BA possessed efficient antidepressant effects on depression, which was possibly related to the inhibition of HMGB1/TLR4/NF-κB pathways.
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- 2019
- Full Text
- View/download PDF
7. Carbocyclic Ring Closure of Aryl C-Glycosides Promoted by Fluoroboric Acid
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Shengbiao Tang, Xin-Shan Ye, De-Cai Xiong, Qin Li, and Qiannan Zheng
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chemistry.chemical_classification ,C glycosides ,Solvent ,chemistry.chemical_compound ,Chemistry ,Fluoroboric acid ,Yield (chemistry) ,Aryl ,Organic Chemistry ,Glycoside ,Ring (chemistry) ,Medicinal chemistry - Abstract
A novel transformation from rhamnose-type C-glycosides to 2-cyclopentenones is described. With the promotion of fluoroboric acid, C-glycosides underwent ring opening and subsequent Nazarov cyclization to afford 2-cyclopentenones in good to excellent yields. The solvent and the concentration of acid are crucial to the yield of this transformation.
- Published
- 2020
8. Engineering a bacterial sialyltransferase for di-sialylation of a therapeutic antibody
- Author
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Yue Wang, Xin-Shan Ye, Liangren Zhang, Mingqun Wang, Kaimeng Liu, Zhenming Liu, and Xiaodong Dou
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chemistry.chemical_classification ,Glycosylation ,biology ,Photobacterium ,Sialyltransferase ,Organic Chemistry ,Mutant ,Mutagenesis (molecular biology technique) ,Protein Engineering ,Biochemistry ,Antibodies ,Sialyltransferases ,carbohydrates (lipids) ,chemistry.chemical_compound ,Enzyme ,chemistry ,Sialic Acids ,biology.protein ,Physical and Theoretical Chemistry ,Antibody ,Bioorthogonal chemistry ,Glycoprotein ,beta-D-Galactoside alpha 2-6-Sialyltransferase - Abstract
Terminal α-2,6-sialylation of N-glycans is a humanized glycosylation that affects the properties and efficacy of therapeutic glycoproteins. Fc di-sialylation (a biantennary N-glycan with two α-2,6-linked sialic acids) of IgG antibodies imparts them with enhanced anti-inflammatory activity and other roles. However, the microheterogeneity of N-glycoforms presents a challenge for therapeutic development. Therefore, controlled sialylation has drawn considerable attention, but direct access to well-defined di-sialylated antibodies remains limited. Herein, a one-pot three-enzyme protocol was developed by engineering a bacterial sialyltransferase to facilitate the modification of therapeutic antibodies with N-acetylneuraminic acid or its derivatives towards optimized glycosylation. To overcome the low proficiency of bacterial sialyltransferase in antibody remodeling, the Photobacterium sp. JT-ISH-224 α-2,6-sialyltransferase (Psp2,6ST) was genetically engineered by terminal truncation and site-directed mutagenesis based on its protein crystal structure. With the optimized reaction conditions and using activity-based screening of various Psp2,6ST variants, a truncated mutant Psp2,6ST (111-511)-His6 A235M/A366G was shown to effectively improve the catalytic efficiency of antibody di-sialylation. Herceptin and the donor substrate promiscuity allow the introduction of bioorthogonal modifications of N-acetylneuraminic acid into antibodies for site-specific conjugation. 2-AB hydrophilic interaction chromatography analysis of the released N-glycans and intact mass characterization confirmed the high di-sialylation of Herceptin via the optimized one-pot three-enzyme reaction. This study established a versatile enzymatic approach for producing highly di-sialylated IgG antibodies. It provides new insights into engineering bacterial sialyltransferase for adaptation to the enzymatic glycoengineering of therapeutic antibodies and the glycosite-specific conjugation of antibodies.
- Published
- 2020
9. C-Glycosylation enabled by N-(glycosyloxy)acetamides
- Author
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Xia Wu, De-Cai Xiong, Bo-Han Li, Meng Liu, Miao Liu, Tian Li, and Xin-Shan Ye
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Reaction conditions ,chemistry.chemical_classification ,Glycosylation ,Silylation ,Aryl ,Organic Chemistry ,Biochemistry ,Enol ,carbohydrates (lipids) ,chemistry.chemical_compound ,chemistry ,Organic chemistry ,lipids (amino acids, peptides, and proteins) ,Glycosyl ,Phenols ,Physical and Theoretical Chemistry ,Alkyl - Abstract
The C-glycosylation of C-nucleophiles including allyltrimethylsilane, silyl enol ethers and phenols with N-(glycosyloxy)acetamides as glycosyl donors has been realized. This protocol provides a convenient and practical route for the synthesis of alkyl C-glycosides and aryl 2-deoxy-β-C-glycosides under mild reaction conditions.
- Published
- 2020
10. Total synthesis of tumor-associated KH-1 antigen core nonasaccharideviaphoto-induced glycosylation
- Author
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Congying Wu, Hong Yang, Bo-Han Li, Yuxin Yin, De-Cai Xiong, Wenlong Yao, and Xin-Shan Ye
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carbohydrates (lipids) ,chemistry.chemical_classification ,chemistry.chemical_compound ,Glycosylation ,KH-1 antigen ,Antigen ,Chemistry ,Stereochemistry ,Organic Chemistry ,Core (graph theory) ,Total synthesis ,lipids (amino acids, peptides, and proteins) ,Glycosidic bond - Abstract
The synthesis of tumor-associated KH-1 antigen core nonasaccharide was achieved. All key glycosidic linkages were efficiently constructed by photo-induced glycosylation. The success of this total synthesis provides an example for the preparation of complex oligosaccharides using light-driven glycosylation reactions.
- Published
- 2020
11. Protecting Groups in Carbohydrate Chemistry: Influence on Stereoselectivity of Glycosylations
- Author
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Jian Guo and Xin-Shan Ye
- Subjects
protecting group ,stereoselectivity ,glycosylation ,carbohydrate ,Organic chemistry ,QD241-441 - Abstract
Saccharides are polyhydroxy compounds, and their synthesis requires complex protecting group manipulations. Protecting groups are usually used to temporarily mask a functional group which may interfere with a certain reaction, but protecting groups in carbohydrate chemistry do more than protecting groups usually do. Particularly, protecting groups can participate in reactions directly or indirectly, thus affecting the stereochemical outcomes, which is important for synthesis of oligosaccharides. Herein we present an overview of recent advances in protecting groups influencing stereoselectivity in glycosylation reactions, including participating protecting groups, and conformation-constraining protecting groups in general.
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- 2010
- Full Text
- View/download PDF
12. Electrochemical Trifluoromethylation of Glycals
- Author
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Zhao-Xiang Luo, De-Cai Xiong, Tian Li, Miao Liu, and Xin-Shan Ye
- Subjects
chemistry.chemical_compound ,Trifluoromethyl ,Trifluoromethylation ,Chemistry ,Organic Chemistry ,Regioselectivity ,Electrochemistry ,Redox mediator ,Combinatorial chemistry ,Oxidation-Reduction - Abstract
Carbohydrates play essential roles in various physiological and pathological processes. Trifluoromethylated compounds have wide applications in the field of medicinal chemistry. Herein, we report a practical and efficient trifluoromethylation of glycals by an electrochemical approach using CF3SO2Na as the trifluoromethyl source and MnBr2 as the redox mediator. A variety of trifluoromethylated glycals bearing different protective groups are obtained in 60-90% yields with high regioselectivity. The successful capture of a CF3 radical indicates that a radical mechanism is involved in this reaction.
- Published
- 2021
13. Synthesis and biological evaluation of bergenin derivatives as new immunosuppressants
- Author
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Youhong Niu, Qin Li, Meng Wang, Xin-Shan Ye, Yan-Fen Wu, Chengcheng Song, and Lihua Deng
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Pharmacology ,biology ,Organic Chemistry ,Pharmaceutical Science ,Bergenin ,Alkylation ,biology.organism_classification ,Biochemistry ,Combinatorial chemistry ,chemistry.chemical_compound ,Chemistry ,chemistry ,Drug Discovery ,Splenocyte ,Molecular Medicine ,Bergenia ,Inhibitory effect ,IC50 ,Biological evaluation - Abstract
Bergenin, which is isolated from Bergenia species, exhibits various pharmacological properties. In the search for new types of immunosuppressants, a series of bergenin derivatives were designed and synthesized, and their immunosuppressive effects were evaluated by the CCK-8 assay. The experimental data demonstrated that compounds 7 and 13 showed the strongest inhibition effects on mouse splenocyte proliferation (IC(50) = 3.52 and 5.39 μM, respectively). Further studies revealed that the inhibitory effect may come from the suppression of both IFN-γ and IL-4 cytokines. Alkylated derivatives of bergenin with n-hexyl and n-heptyl on the two phenolic hydroxyl groups showed better inhibitory activities. The hydrophobicity of bergenin derivatives, the configuration of the 4-OH in bergenin, and the ability to form hydrogen bonds of the substituents on the C-4 position are important to the immunosuppressive activity. This work proved that the modifications of bergenin may represent a new route to the discovery of a new class of immunosuppressive agents.
- Published
- 2021
14. Fabrication of Tubular g‐C 3 N 4 with N‐Defects and Extended π‐Conjugated System for Promoted Photocatalytic Hydrogen Production
- Author
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Guifang Ge, Zhongkui Zhao, and Xin Shan
- Subjects
Fabrication ,Materials science ,Organic Chemistry ,Graphitic carbon nitride ,Conjugated system ,Catalysis ,Inorganic Chemistry ,chemistry.chemical_compound ,Chemical engineering ,chemistry ,Photocatalysis ,Hydrogen evolution ,Physical and Theoretical Chemistry ,Hydrogen production - Published
- 2019
15. Rapid glycosylation of 2′-benzoylphenyl glycosides promoted by TfOH
- Author
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Da-Ke Liu, Qin Li, De-Cai Xiong, Xia Wu, and Xin-Shan Ye
- Subjects
chemistry.chemical_classification ,Glycosylation ,010405 organic chemistry ,Organic Chemistry ,Glycoside ,Substrate (chemistry) ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,carbohydrates (lipids) ,chemistry.chemical_compound ,chemistry ,lipids (amino acids, peptides, and proteins) ,Glycosyl - Abstract
A new glycosylation protocol based on 2′-benzoylphenyl glycosides has been developed. These glycosyl donors could be rapidly activated by TfOH at room temperature. The donors are readily available. The reaction exhibited a broad substrate scope and coupled products were obtained in high yields.
- Published
- 2019
16. Synthesis of N-Substituted Iminosugar Derivatives and Evaluation of Their Immunosuppressive Activities
- Author
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Xin-Shan Ye, Zhuo Lv, Youhong Niu, Qin Li, and Chengcheng Song
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Male ,Iminosugar ,Pharmacology ,Alkylation ,010402 general chemistry ,Inhibitory postsynaptic potential ,01 natural sciences ,Biochemistry ,Interferon-gamma ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Amide ,Drug Discovery ,Splenocyte ,Animals ,General Pharmacology, Toxicology and Pharmaceutics ,IC50 ,Cells, Cultured ,Cell Proliferation ,Mice, Inbred BALB C ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Imino Sugars ,0104 chemical sciences ,Molecular Medicine ,Interleukin-4 ,Immunosuppressive Agents ,Spleen - Abstract
It is important to find more effective and safer immunosuppressants, because clinically used immunosuppressive agents have significant side effects. A series of N-substituted iminosugar derivatives were designed and synthesized, and their immunosuppressive effects were evaluated by the CCK-8 assay. The results revealed that iminosugars 10 e and 10 i, that is, (3R,4S)-1-(4-heptyloxylphenylethyl)pyrrolidine-3,4-diol and (3R,4S)-1-[2-(2-chloro-4-(p-tolylthio)-phenyl-1-yl)ethyl]pyrrolidine-3,4-diol, respectively, exhibited the strongest inhibitory effects on mouse splenocyte proliferation (IC50 =2.16 and 2.48 μm, respectively), whereas the iminosugars containing an amide group near the hydrophilic head (compounds 10 j-n) exhibited no inhibitory effects. Further studies revealed that the inhibitory effects on splenocyte proliferation may have come from the suppression of both IFN-γ and IL-4 cytokines. Our results suggest that synthetic iminosugars, especially compounds 10 e and 10 i, hold potential as immunosuppressive agents.
- Published
- 2018
17. Chemical synthesis and biological evaluation of penta- to octa- saccharide fragments of Vi polysaccharide fromSalmonella typhi
- Author
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Meng-Man Wei, Xin-Shan Ye, Gao-Lan Zhang, De-Cai Xiong, Yu-Feng Ma, Chengcheng Song, and Xiu-Jing Zheng
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Chemistry ,Pentamer ,Organic Chemistry ,Glycoside ,Oligosaccharide ,010402 general chemistry ,Salmonella typhi ,Polysaccharide ,01 natural sciences ,Chemical synthesis ,Epitope ,0104 chemical sciences ,Biochemistry ,Conjugate vaccine - Abstract
Vi antigen is the capsular polysaccharide of Salmonella typhi, which can cause typhoid fever. With the increasing threat of antiboitic resistance, vaccination against Salmonella typhi is a preferred way to prevent this disease. Chemical synthesis of fragments of Vi antigen is in urgent need for the development of structure-homogeneous and quality-controlled oligosaccharide vaccines. However, it is extremely challenging to synthesize large oligosaccharide fragments of Vi antigen owing to the exclusive α-1,4-linkage of polyaminogalacturonates. Herein, a series of Vi oligosaccharides ranging from pentamer to octamer were efficiently prepared using 2,3-N,O-oxazolidinone protected glycosides as building blocks based on the preactivation protocol. The heptasaccharide and octasaccharide fragments were synthesized for the first time. The competitive ELISA evaluation suggested that the hexasaccharide might be the minimum epitope of Vi antigen, which provides a significant guidance for the future development of Vi oligosaccharide vaccines.
- Published
- 2018
18. General Approach to Five-Membered Nitrogen Heteroaryl C-Glycosides Using a Palladium/Copper Cocatalyzed C–H Functionalization Strategy
- Author
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Shuo Zhang, Xin-Shan Ye, and Youhong Niu
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C glycosides ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Copper ,Nitrogen ,0104 chemical sciences ,Yield (chemistry) ,Organic chemistry ,Surface modification ,Physical and Theoretical Chemistry ,Palladium - Abstract
A general approach to the synthesis of diverse heteroaryl-C-Δ1,2-glycosides has been developed by employing the Pd(OAc)2/CuI cocatalyzed direct cross-coupling of five-membered nitrogen heterocycles with 1-iodoglycals in a C–H activation manner. Using this method, 27 examples of heteroaryl-C-Δ1,2-glycosides, containing indoles, thiazoles, benzothiazoles, imidazoles, benzimidazoles, and benzoxazoles as aglycones were obtained in 43–99% yield.
- Published
- 2017
19. Design, synthesis and cytotoxic evaluation of a novel series of benzo[d]thiazole-2-carboxamide derivatives as potential EGFR inhibitors
- Author
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Chao Zhang, Xin-Shan Deng, Guang-Peng Meng, Wu Jiaofeng, Chun Hu, Qing-Chun Zhao, Lan Zhang, and Xue-Song Li
- Subjects
biology ,010405 organic chemistry ,medicine.drug_class ,Organic Chemistry ,Carboxamide ,Pharmacology ,biology.organism_classification ,01 natural sciences ,Molecular biology ,0104 chemical sciences ,HeLa ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,chemistry ,Cell culture ,biology.protein ,medicine ,Cytotoxic T cell ,Epidermal growth factor receptor ,General Pharmacology, Toxicology and Pharmaceutics ,Thiazole ,Cytotoxicity ,EGFR inhibitors - Abstract
A novel series of benzo[d]thiazole-2-carboxamide derivatives have been de novo designed based on virtual screening methods. The target compounds were synthesized and evaluated for the cytotoxicity against epidermal growth factor receptor high-expressed cancer cell lines (A549, HeLa, and SW480), epidermal growth factor receptor low-expressed cell line (HepG2) and human liver normal cell line (HL7702). Several target compounds have showed moderate to excellent potency against A549, HeLa, and SW480 and weak cytotoxic effects against HepG2, which implies they are probably epidermal growth factor receptor inhibitors. And scarcely did they exhibit any activities against HL7702, which signifies they are likely to overcome the nonspecific toxicity against normal cells. Especially, the compound 6-[2-(diethylamino)-2-oxoethoxy]-N-(furan-2-ylmethyl)benzo[d]thiazole-2-carboxamide (6i) was identified as a promising agent, exhibiting the most potent cytotoxic activities with IC50 values of 4.05, 12.17, 6.76 μM against the A549, HeLa, and SW480 cell lines, respectively.
- Published
- 2017
20. Synthesis and biological evaluation of N-arylated-lactam-type iminosugars as potential immunosuppressive agents
- Author
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Youhong Niu, Qin Li, Chengcheng Song, Xin-Shan Ye, Hai-Qian Liu, and Tao Li
- Subjects
Drug ,Lactams ,media_common.quotation_subject ,Molecular Conformation ,Iminosugar ,Pharmacology ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Jurkat Cells ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Splenocyte ,Animals ,Humans ,Structure–activity relationship ,MTT assay ,Physical and Theoretical Chemistry ,IC50 ,Cell Proliferation ,media_common ,Dose-Response Relationship, Drug ,010405 organic chemistry ,Chemistry ,Cell growth ,Organic Chemistry ,Combinatorial chemistry ,Imino Sugars ,0104 chemical sciences ,Lactam ,Immunosuppressive Agents ,Spleen - Abstract
Since the immunosuppressive agents currently used in clinics have significant side effects, it is very important to search for new effective and safe immunosuppressants. Iminosugars as a new class of immunosuppressants are less explored. In this report, 24 new N-arylated iminosugar derivatives, including d-talo and d-galacto epimers, were designed and synthesized, and their immunosuppressive effects were evaluated by MTT assay. The experimental data demonstrated that compound 20 showed the strongest inhibition effect (IC50 = 6.94 μM). Further studies revealed that the inhibitory effects on splenocyte proliferation may come from the suppression of both IFN-γ and IL-4 cytokines. The preliminary structure-activity relationship (SAR) analysis suggested that N-arylated d-galacto-type iminosugars showed better inhibitory activities than d-talo-type analogues. The SAR analysis also showed that the inhibition effect of iminosugars can be improved by decreasing the polarity or increasing the hydrophobicity. These results may be beneficial to the discovery of new iminosugar derivatives as immunosuppressive agents.
- Published
- 2017
21. A general approach to C-Acyl glycosides via palladium/copper Co-catalyzed coupling reaction of glycosyl carbothioates and arylboronic acids
- Author
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Li-Na Wang, Qing-Hui Cai, Youhong Niu, Xin-Shan Ye, and Qin Li
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Organic Chemistry ,Substrate (chemistry) ,chemistry.chemical_element ,Glycoside ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Copper ,Combinatorial chemistry ,Coupling reaction ,0104 chemical sciences ,Catalysis ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Glycosyl ,Palladium - Abstract
A general and efficient approach to the synthesis of various C-acyl glycosides has been developed via Pd2(dba)3/CuTC co-catalyzed cross-coupling reaction of glycosyl carbothioates with arylboronic acids. The reaction showed a broad substrate scope and 25 examples were exhibited in 61%–97% isolated yields. Furthermore, this reaction was applied to the gram-scale preparation of C-acyl glycosides. The coupled products can be further transformed into diverse biologically useful compounds, as exemplified by the synthesis of protected sergliflozin-A mimics.
- Published
- 2021
22. 3-Butenyloxycarbonyl as a new hydroxyl protecting group in carbohydrate synthesis
- Author
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Xin-Shan Ye, Youhong Niu, and Nana Zeng
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Glycosylation ,010405 organic chemistry ,Organic Chemistry ,Carbohydrate synthesis ,010402 general chemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Organic chemistry ,Oxidative cleavage ,Protecting group - Abstract
3-Butenyloxycarbonyl (Bloc) has been identified as a new hydroxyl protecting group, which can be introduced under mild conditions in high yields and selectively removed by OsO4/NaIO4/2,6-lutidine in CH3CN–H2O without affecting most commonly-used protecting groups. Moreover, this new protecting group is inert under glycosylation conditions.
- Published
- 2016
23. Stereoselective Koenigs-Knorr Glycosylation Catalyzed by Urea
- Author
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Xiaowei Wu, Xin-Shan Ye, De-Cai Xiong, and Lifeng Sun
- Subjects
animal structures ,Anomer ,Glycosylation ,Stereochemistry ,010405 organic chemistry ,fungi ,macromolecular substances ,General Chemistry ,General Medicine ,010402 general chemistry ,01 natural sciences ,Catalysis ,0104 chemical sciences ,carbohydrates (lipids) ,chemistry.chemical_compound ,chemistry ,Organocatalysis ,Urea ,Organic chemistry ,lipids (amino acids, peptides, and proteins) ,Glycosyl ,Stereoselectivity ,Selectivity ,Phosphine - Abstract
A stereoselective Koenigs-Knorr glycosylation reaction under the catalysis of urea is described. This method is characterized by urea-mediated hydrogen-bond activation and subsequent glycosylation with glycosyl chlorides or bromides. Excellent yields and high anomeric selectivity can be achieved in most cases. Moreover, the low α-stereoselectivity of glycosylations observed when using perbenzylated glucosyl donors can be greatly improved by the addition of tri-(2,4,6-trimethoxyphenyl)phosphine (TTMPP).
- Published
- 2016
24. A new GLP-1 analogue with prolonged glucose-lowering activity in vivo via backbone-based modification at the N-terminus
- Author
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Xin-Shan Ye, Youhong Niu, Yan-Fen Wu, Jingjing Zhu, An-Qi Yang, and Xiaohui Bai
- Subjects
Blood Glucose ,0301 basic medicine ,Stereochemistry ,Clinical Biochemistry ,Pharmaceutical Science ,Endogeny ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Dipeptidyl peptidase ,03 medical and health sciences ,chemistry.chemical_compound ,Glucagon-Like Peptide 1 ,In vivo ,Amide ,Drug Discovery ,Humans ,Hypoglycemic Agents ,GLP-1 Analogue ,Receptor ,Molecular Biology ,Molecular Structure ,Chemistry ,Organic Chemistry ,In vitro ,0104 chemical sciences ,N-terminus ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Molecular Medicine - Abstract
Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic hormone with wonderful glucose-lowering activity. However, its clinical use in type II diabetes is limited due to its rapid degradation at the N-terminus by dipeptidyl peptidase IV (DPP-IV). Among the N-terminal modifications of GLP-1, backbone-based modification was rarely reported. Herein, we employed two backbone-based strategies to modify the N-terminus of tGLP-1. Firstly, the amide N-methylated analogues 2–6 were designed and synthesized to make a full screening of the N-terminal amide bonds, and the loss of GLP-1 receptor (GLP-1R) activation indicated the importance of amide H-bonds. Secondly, with retaining the N-terminal amide H-bonds, the β-peptide replacement strategy was used and analogues 7–13 were synthesized. By two rounds of screening, analogue 10 was identified. Analogue 10 greatly improved the DPP-IV resistance with maintaining good GLP-1R activation in vitro, and showed approximately a 4-fold prolonged blood glucose-lowering activity in vivo in comparison with tGLP-1. This modification strategy will benefit the development of GLP-1-based anti-diabetic drugs.
- Published
- 2016
25. Thermal Decomposition Kinetics of Hexanitrohexaazaisowurtzitane/Ammonium Perchlorate
- Author
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Qingjie Jiao, Ming-Xin Shan, Kang-Kang Wang, Yan-Li Zhu, Jing-Si Wang, and Zheng Xiaodi
- Subjects
Organic Chemistry ,Inorganic chemistry ,Chemical process of decomposition ,Kinetics ,Thermal decomposition ,Analytical chemistry ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Ammonium perchlorate ,01 natural sciences ,Decomposition ,0104 chemical sciences ,Thermogravimetry ,Hexanitrohexaazaisowurtzitane ,chemistry.chemical_compound ,chemistry ,Materials Chemistry ,0210 nano-technology ,Thermal analysis - Abstract
The thermal decomposition kinetics of hexanitrohexaazaisowurtzitane/ ammonium perchlorate (HNIW/AP) have been investigated by thermogravimetry- differential scanning calorimetry-mass spectrometry (TG-DSC-MS) simultaneous analysis. TG showed that there were three weight loss processes for the thermal decomposition of the HNIW/AP mixture. The first was ascribed mainly to the thermal decomposition of HNIW, while the second and third were assigned to that of AP. The presence of AP has little effect on the thermal decomposition process of the HNIW component. The apparent activation energy of the thermal decomposition of the HNIW component, calculated by the Kissinger method, was little changed compared to that of neat HNIW. The addition of HNIW to AP caused the onset and end temperatures of the thermal decomposition to be decreased and the decomposition process to be shortened. The high-temperature and low- temperature decomposition processes of AP became blurred in the presence of HNIW, and this was supported by the MS results.
- Published
- 2016
26. Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines
- Author
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Chengcheng Song, Xiu-Jing Zheng, An Xiao, Xin-Shan Ye, Yue Gui, and Chang-Xin Huo
- Subjects
Synthetic vaccine ,010402 general chemistry ,Cancer Vaccines ,digestive system ,01 natural sciences ,Biochemistry ,Mice ,Antigen ,Cell Line, Tumor ,Neoplasms ,Animals ,Humans ,Antigens, Tumor-Associated, Carbohydrate ,Physical and Theoretical Chemistry ,skin and connective tissue diseases ,neoplasms ,MUC1 ,chemistry.chemical_classification ,Mice, Inbred BALB C ,biology ,010405 organic chemistry ,Chemistry ,Immune Sera ,Immunogenicity ,Mucin-1 ,Organic Chemistry ,Glycopeptides ,digestive system diseases ,biological factors ,Glycopeptide ,0104 chemical sciences ,Hemocyanins ,biology.protein ,Female ,Immunization ,Antibody ,Glycoprotein ,Keyhole limpet hemocyanin - Abstract
Glycoprotein MUC1 is an attractive target for anti-tumor vaccine development. However, the weak immunogenicity of MUC1 remains a significant problem. To solve this problem, several STn derivatives with N-acetyl modifications were synthesized and incorporated into a 20-amino acid MUC1 tandem repeat sequence. The modified STn-MUC1 glycopeptides were further connected to a carrier protein keyhole limpet hemocyanin (KLH). The immunological effects of these synthetic vaccine conjugates were evaluated using the BALB/c mouse model. The results showed that vaccine V2 elicited higher titers of antibodies which cross-reacted with the native STn-MUC1 antigen. Moreover, the elicited antisera reacted with the STn-MUC1 antigen-positive tumor cells, indicating that the carbohydrate antigen modification strategy may hold potential to overcome the weak immunogenicity of natural MUC1 glycopeptides.
- Published
- 2016
27. Light-driven highly efficient glycosylation reactions
- Author
-
Runze Mao, Xin-Shan Ye, De-Cai Xiong, Qin Li, Jinyou Duan, and Fan Guo
- Subjects
Glycosylation ,010405 organic chemistry ,Organic Chemistry ,Substrate (chemistry) ,010402 general chemistry ,Photochemistry ,01 natural sciences ,0104 chemical sciences ,carbohydrates (lipids) ,chemistry.chemical_compound ,chemistry ,Light driven ,lipids (amino acids, peptides, and proteins) ,Glycosyl ,Organic synthesis - Abstract
Glycosylation is unarguably the most important reaction in the field of glycochemistry. Photo-initiated reactions hold extraordinary potential in organic synthesis. Herein we report a novel light-driven strategy for the activation of thioglycosides via the merger of a CF3 radical pathway followed by the subsequent glycosylation with glycosyl acceptors. This protocol could efficiently activate thioglycosides, thereby greatly enhancing the substrate scope of reactions. In particular, the glycosylation reactions, which are completely inert under the existing photo-induced glycosylation conditions, proceeded smoothly in high yields. Many common protective groups were well tolerated under the coupling conditions. Both UV and visible light or even sunlight were used as the source of light for the reactions. The high efficiency of this light-driven glycosylation protocol was further highlighted by the rapid one-pot sequential assembly of oligosaccharides.
- Published
- 2016
28. Indolo-quinoline boron difluoride dyes: synthesis and spectroscopic properties
- Author
-
Xiao-Ping Cao, Xin-Shan Ye, Xiaojun Yao, Hui-Xin Luo, Youhong Niu, and Xiaojie Jin
- Subjects
010405 organic chemistry ,Organic Chemistry ,Quinoline ,010402 general chemistry ,Photochemistry ,01 natural sciences ,Biochemistry ,Fluorescence ,0104 chemical sciences ,chemistry.chemical_compound ,Suzuki reaction ,chemistry ,Boron difluoride ,Physical and Theoretical Chemistry - Abstract
Novel indolo-quinoline compounds were efficiently prepared via a Povarov-type reaction, and the structures were further modified by a Suzuki coupling reaction. The corresponding BF2-rigidified complexes were prepared and their spectroscopic properties were characterized with large Stokes shifts (up to 211 nm) and up to near-infrared (NIR) wavelength (667 nm). The synthetic complexes could be used as new fluorescent dyes.
- Published
- 2016
29. Direct C–H Trifluoromethylation of Glycals by Photoredox Catalysis
- Author
-
De-Cai Xiong, Xin-Shan Ye, and Bang Wang
- Subjects
Hydrocarbons, Fluorinated ,Light ,Molecular Structure ,Trifluoromethylation ,Chemistry ,Organic Chemistry ,Photoredox catalysis ,Alkenes ,Photochemistry ,Methylation ,Biochemistry ,Catalysis ,Reagent ,Photocatalysis ,Molecule ,Moiety ,Glycosides ,Physical and Theoretical Chemistry ,Visible spectrum - Abstract
A mild, efficient, and practical transformation for the direct C-H trifluoromethylation of glycals under visible light has been reported for the first time. This reaction employed fac-Ir(3+)(ppy)3 as the photocatalyst, Umemoto's reagent as the CF3 source, and a household blue LED or sunlight as the light source. Glycals bearing both electron-withdrawing and -donating protective groups performed this reaction smoothly. This visible light-mediated trifluoromethylation reaction was highlighted by the trifluoromethylation of the biologically important Neu2en moiety.
- Published
- 2015
30. Cyclopropenes for the Synthesis of Cyclopropane-Fused Dihydroquinolines and Benzazepines
- Author
-
Youhong Niu, Xiao-Ping Cao, Xin-Shan Ye, and Hui-Xin Luo
- Subjects
chemistry.chemical_compound ,Benzazepines ,Chemistry ,Organic chemistry ,Regioselectivity ,General Chemistry ,Ring (chemistry) ,Isomerization ,Combinatorial chemistry ,Benzazepine ,Cyclopropane - Abstract
An efficient method for the construction of cyclopropane-fused dihydroquinolines was established by a novel Povarov-type three-component reaction of aromatic aldehydes, anilines and cyclopropenes in the presence of trifluoromethanesulfonic acid. The reaction proceeded in a regioselective and diastereoselective manner. Furthermore, the dihy-droquinolines were smoothly converted to benzazepine derivatives via a ring opening/isomerization sequence, further expanding the synthetic scope.
- Published
- 2015
31. Advances in the Synthesis of C-Glycosides from Glycals
- Author
-
De-Cai Xiong, Jinhe Bai, Zhenyan Guo, Miao Liu, and Xin-Shan Ye
- Subjects
C glycosides ,Chemistry ,Organic Chemistry ,Organic chemistry - Published
- 2020
32. O-Glycosylation Enabled by N-(Glycosyloxy)acetamides
- Author
-
Xin-Shan Ye, Bo-Han Li, De-Cai Xiong, and Miao Liu
- Subjects
Glycosylation ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Chemical glycosylation ,Leaving group ,Substrate (chemistry) ,010402 general chemistry ,01 natural sciences ,Combinatorial chemistry ,0104 chemical sciences ,chemistry.chemical_compound ,Microwave irradiation ,Glycosyl ,Oligosaccharide synthesis - Abstract
A novel glycosylation protocol has been established by using N-(glycosyloxy)acetamides as glycosyl donors. The N-oxyacetamide leaving group in donors could be rapidly activated in the presence of Cu(OTf)2 or SnCl4 under microwave irradiation. This glycosylation process afforded the coupled products in high yields, and the reaction enjoyed a broad substrate scope, even for disarmed donors and hindered acceptors. The easy availability of the donors, the high stability of N-(glycosyloxy)acetamides, and the small leaving group make this method very practical.
- Published
- 2018
33. Stereocontrolled Synthesis of 2-Deoxy- C-glycopyranosyl Arenes Using Glycals and Aromatic Amines
- Author
-
Shengbiao Tang, Qiannan Zheng, Xin-Shan Ye, Shende Jiang, De-Cai Xiong, and Qin Li
- Subjects
chemistry.chemical_compound ,010405 organic chemistry ,Chemistry ,Aryl ,Organic Chemistry ,Substrate (chemistry) ,Stereoselectivity ,Physical and Theoretical Chemistry ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Combinatorial chemistry ,0104 chemical sciences - Abstract
An efficient and stereoselective one-pot, two-step tandem α-arylation of glycals from readily available aryl amines via stable diazonium salts has been developed. Moreover, the stereoselective preparation of the challenging β- C-glycosyl arenes by the anomerization of α- C-glycosides using HBF4 is also described. This protocol has a broad substrate scope and a wide functional-group tolerance. It can be used for the gram-scale preparation of 3-oxo- C-glycosides, which are versatile substrates for the preparation of many biologically important C-glycosides.
- Published
- 2018
34. Frontispiece: Synthetic Glycans and Glycomimetics: A Promising Alternative to Natural Polysaccharides
- Author
-
Gao-Lan Zhang and Xin-Shan Ye
- Subjects
chemistry.chemical_classification ,Glycan ,chemistry ,biology ,Biochemistry ,Glycomimetic ,Organic Chemistry ,biology.protein ,General Chemistry ,Oligosaccharide ,Polysaccharide ,Catalysis - Published
- 2018
35. Synthetic Glycans and Glycomimetics: A Promising Alternative to Natural Polysaccharides
- Author
-
Xin-Shan Ye and Gao-Lan Zhang
- Subjects
Glycan ,Biocompatible Materials ,010402 general chemistry ,Polysaccharide ,01 natural sciences ,Catalysis ,Glycomimetic ,Polysaccharides ,medicine ,Carbohydrate Conformation ,Animals ,chemistry.chemical_classification ,Vaccines, Synthetic ,biology ,Bacteria ,010405 organic chemistry ,Heparin ,Organic Chemistry ,Polysaccharides, Bacterial ,Anticoagulants ,General Chemistry ,Oligosaccharide ,Carbohydrate ,0104 chemical sciences ,chemistry ,Biochemistry ,biology.protein ,Carbohydrate conformation ,Conjugate ,medicine.drug - Abstract
A large quantity of polysaccharide-derived conjugate vaccines have been developed to combat various pathogenic infections. Another prominent polysaccharide, heparin, is listed as an essential drug by the World Health Organization (WHO) to treat thrombus. One of their common problems is that they all derive from natural polysaccharides. Specifically, capsular polysaccharides are mainly obtained from bacterial fermentation and unfractionated heparin is extracted from animal tissues such as porcine mucosa. The quality of natural polysaccharides is inconsistent and traces of contamination would cause a disaster. By contrast, the use of chemical or chemoenzymatic methods could provide structurally homogeneous and quality-controlled glycans. To date, large numbers of polysaccharide fragments and their analogues have been synthesized and evaluated. Some of them even showed comparable activities to their corresponding natural polysaccharides. Here, the latest advances in these synthetic glycan analogues ranging from carbohydrate-based vaccines, heparin-related therapeutics and glycomimetics of polysaccharides are summarized.
- Published
- 2017
36. An Alternative Preparation of Azides from Amines via Diazotransfer with Triflyl Azide
- Author
-
Yuqian Ye, Xin-Shan Ye, and Xingdi Wang
- Subjects
Solvent ,chemistry.chemical_compound ,Aqueous solution ,chemistry ,Reagent ,Click chemistry ,Organic chemistry ,Azide ,Solubility ,Bioorthogonal chemistry ,Toluene - Abstract
56Azides are an important group of compounds in synthetic chemistry and chemical biology. Azides are sterically less demanding and have greater solubility compared to carbamates and amides. 1 Uses of azides include photoaffinity labeling of biomolecules. They are precursors in the “click chemistry” reactions to form linkages for various conjugates and bioorthogonal chemical reporters. 2 Azides can be prepared from amines via the diazotransfer reaction with triflyl azide (TfN3) 1,3,4 at mild reaction conditions and in good yield with complete retention of configuration. The drawback of the protocol is that a three-component solvent system of H2O/MeOH/CH2Cl2 (v/v/v =3:10:3) and a large excess of reagent (TfN3) must be used. This complicated solvent system was developed by Wong’s group from the earlier method, in which Tf2O was directly added to a biphasic mixture of CH2Cl2 and saturated aqueous NaN3. 5 In the presence of water, Tf2O would be hydrolyzed inevitably, and therefore an excess amount of Tf2O and NaN3, both highly toxic, had to be used. Also, the formed TfN3 is dissolved in CH2Cl2, which is not a good solvent for many substrates for the subsequent diazotransfer reaction. Wong developed a homogeneous phase by carefully mixing H2O, MeOH, and CH2Cl2, 6 but a slight difference in the ratio of the solvents may still lead to a somewhat unpredictable result. In 2006, Titz and co-workers developed a solvent system of MeOH/toluene/H2O, 7 but it is not a convenient solvent for a large number of carbohydrate substrates.
- Published
- 2017
37. Synthesis of novel N-glycoside derivatives via CuSCN-catalyzed reactions and their SGLT2 inhibition activities
- Author
-
Xin-Shan Ye, Shao-Tao Bai, De-Cai Xiong, Youhong Niu, and Yan-Fen Wu
- Subjects
chemistry.chemical_classification ,chemistry.chemical_compound ,chemistry ,Stereochemistry ,Organic Chemistry ,Drug Discovery ,Triazole ,Click chemistry ,Glycoside ,Carbohydrate ,Biochemistry ,Coupling reaction ,Catalysis - Abstract
A convenient approach to the synthesis of novel triazole- N -glycoside derivatives was developed via CuSCN-catalyzed click reaction and Ullmann-type coupling reaction for the first time. The SGLT2 inhibitory activities of these synthetic N -glycosides were evaluated, and some compounds showed moderate SGLT2 inhibition activities at 100 nM. The results could benefit the discovery of new SGLT2 inhibitors for the treatment of diabetes.
- Published
- 2015
38. Synthetic phenylethanoid glycoside derivatives as potent neuroprotective agents
- Author
-
Yingguo Liu, Binhan Yu, Pu Xiaoping, Xin-Shan Ye, De-Cai Xiong, and Li Xiaxi
- Subjects
Drug ,Antioxidant ,Cell Survival ,media_common.quotation_subject ,medicine.medical_treatment ,Cell ,Chemistry Techniques, Synthetic ,PC12 Cells ,Neuroprotection ,Permeability ,Structure-Activity Relationship ,chemistry.chemical_compound ,Drug Discovery ,Edaravone ,medicine ,Animals ,Glycosides ,media_common ,Pharmacology ,chemistry.chemical_classification ,Organic Chemistry ,Glycoside ,Free Radical Scavengers ,General Medicine ,Phenylethanoid ,Rats ,Neuroprotective Agents ,medicine.anatomical_structure ,nervous system ,chemistry ,Biochemistry ,Blood-Brain Barrier ,Drug Design ,Intracellular - Abstract
Several phenylethanoid glycoside derivatives were designed and synthesized. Most of the synthetic compounds showed significant neuroprotective effects, including antioxidative and anti-apoptotic properties. Specifically, target compounds displayed potent effects against various toxicities such as H2O2 and 6-hydroxydopamine (6-OHDA) in PC12 cells. Among the synthetic derivatives, three compounds (5, 6, 8) exhibited much superior activities to the marketed drug Edaravone. The compounds were able to prevent the 6-OHDA-induced damage in PC12 cells in a dose-dependent manner. The anti-apoptotic effects could be observed via cell morphological changes. Moreover, the compounds significantly reduced the intracellular ROS increase resulting from 6-OHDA treatment. The preliminary structure-activity relationships were also explored. Compounds 5, 6, 8 may hold the potential as promising neuroprotective agents and new lead compounds for the treatment of neurodegenerative diseases or cerebral ischemia.
- Published
- 2015
39. Additive-controlled stereoselective glycosylations of 2,3-oxazolidinone protected glucosamine or galactosamine thioglycoside donors with phenols based on preactivation protocol
- Author
-
Xin-Shan Ye, Qi Qin, and De-Cai Xiong
- Subjects
chemistry.chemical_classification ,Glucosamine ,Glycosylation ,Organic Chemistry ,Glycoside ,Galactosamine ,Stereoisomerism ,General Medicine ,Biochemistry ,Substrate Specificity ,Analytical Chemistry ,chemistry.chemical_compound ,Phenols ,chemistry ,Thioglycosides ,Phenol ,Organic chemistry ,Stereoselectivity ,Oxazolidinones - Abstract
Stereo-controllable glycosylation reactions of 2,3-oxazolidinone protected glucosamine thioglycoside donor with different phenol acceptors based on preactivation protocol, are described. It was found that BF3·Et2O worked as α-directing additive, while TTBP acted as β-directing additive. Simply by altering additives, either α-aryl glycosides or β-aryl glycosides were achieved in a stereoselective manner. The additives were also applied to the stereoselective glycosylation reactions of 2,3-oxazolidinone protected galactosamine donor with phenol substrates.
- Published
- 2015
40. Synthetic and immunological studies of N-acyl modified S-linked STn derivatives as anticancer vaccine candidates
- Author
-
Chang-Cheng Liu, Xiu-Jing Zheng, Xin-Shan Ye, An Xiao, Chang-Xin Huo, Shuang Sun, and Zhuo Lv
- Subjects
Male ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Glycan ,biology ,Glycoconjugate ,Carbohydrate chemistry ,Immunogenicity ,Organic Chemistry ,Cancer Vaccines ,Biochemistry ,Antigen ,chemistry ,biology.protein ,Animals ,Antigens, Tumor-Associated, Carbohydrate ,Female ,Immunization ,Physical and Theoretical Chemistry ,Antibody ,Glycoconjugates ,Keyhole limpet hemocyanin ,Conjugate - Abstract
It is well known that tumor cells express some aberrant glycans, termed tumor-associated carbohydrate antigens (TACAs). TACAs are good targets for the development of carbohydrate-based anticancer vaccines. However, one of the major problems is that carbohydrate antigens possess a weak immunogenicity. To tackle this problem, a number of unnatural N-modified S-linked STn analogues were designed and prepared. Reaction of the modified STn disaccharides with bifunctional adipic acid p-nitrophenyl diester provided the corresponding activated esters, which was followed by the conjugation with keyhole limpet hemocyanin (KLH), affording the corresponding protein conjugates. The immunological properties of these glycoconjugates were evaluated in a mouse model. The results showed that the modified glycoconjugates stimulated the production of IgG antibodies that are capable of recognizing the naturally occurring STn antigen, helping the discovery of carbohydrate-based anticancer vaccine candidates.
- Published
- 2015
41. Rapid probing of sialylated glycoproteins in vitro and in vivo via metabolic oligosaccharide engineering of a minimal cyclopropene reporter
- Author
-
Yang Yu, Hui-Xin Luo, Xin-Shan Ye, Cong Wang, Jingjing Zhu, De-Cai Xiong, Guihua Tai, Yuqian Ye, and Ming-Jie Han
- Subjects
Cyclopropanes ,Glycan ,Oligosaccharides ,Biochemistry ,Metabolic engineering ,Mice ,chemistry.chemical_compound ,In vivo ,Cell Line, Tumor ,Labelling ,Animals ,Humans ,Physical and Theoretical Chemistry ,Glycoproteins ,chemistry.chemical_classification ,Staining and Labeling ,biology ,Organic Chemistry ,Oligosaccharide ,N-Acetylneuraminic Acid ,Sialic acid ,Metabolic Engineering ,chemistry ,Molecular Probes ,biology.protein ,Bioorthogonal chemistry ,Glycoprotein - Abstract
ManNAc analogues are important chemical tools for probing sialylation dynamically via metabolic oligosaccharide engineering (MOE). The size of N-acyl and the nature of the chemical handle are two determinants of metabolic incorporation efficiency. We demonstrated a minimal, stable, bioorthogonal, and reactive N-Cp (N-(cycloprop-2-ene-1-ylcarbonyl)) group and the imaging of sialylated glycans using Ac4ManNCp in vitro and in vivo. The results revealed that the Cp group can efficiently be incorporated into the cellular sialic acid and detected rapidly by the reaction with FITC-Tz in different cells. The metabolic incorporation efficiency of non-cytotoxic Ac4ManNCp is not only superior to Ac4ManNMCp, but also superior to the widely-used Ac4ManNAz in some cell lines. Moreover, when Ac4ManNCp was administered to mice, a rapid and intense labelling of splenocytes as well as glycoproteins of sera and organs was observed. This is the first reported metabolic labelling of cyclopropene-modified sugars in vivo. Therefore, Ac4ManNCp is a powerful probe for efficient and rapid MOE and it may find wide applications in the labelling of glycans.
- Published
- 2015
42. Synthesis of N-dialkylphosphoryl iminosugar derivatives and their immunosuppressive activities
- Author
-
Xin-Shan Ye, Guihua Tai, De-Cai Xiong, Xuemei Yang, and Chengcheng Song
- Subjects
Stereochemistry ,Iminosugar ,Biochemistry ,Interferon-gamma ,Mice ,Structure-Activity Relationship ,medicine ,Splenocyte ,Animals ,Structure–activity relationship ,Interferon gamma ,Secretion ,Physical and Theoretical Chemistry ,Alkyl ,Interleukin 4 ,Cell Proliferation ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Molecular Structure ,Organic Chemistry ,Imino Sugars ,chemistry ,Cytokine secretion ,Interleukin-4 ,Immunosuppressive Agents ,Spleen ,medicine.drug - Abstract
Twelve novel N-dialkylphosphoryliminosugar derivatives were synthesized and their immunosuppressive activities were evaluated on the proliferation of the mouse splenocytes and the secretion of IFN-γ and IL-4. The experimental data demonstrated that the iminosugars with the double long alkyl chains exhibited better inhibitory effects than those with the single long alkyl chain, and the iminosugars with the 10-carbon linear alkyl chain exhibited the strongest immunosuppressive activities. The assay of the cytokine secretion showed that the introduction of dialkyl chains on iminosugars could regulate the polarization of immune inhibition by varying the length of the alkyl chains. The disclosure of the structure-activity relationships may benefit the structural modifications of iminosugars to find new types of immunosuppressive agents.
- Published
- 2015
43. KOtBu-mediated aromatic O-glycosylation of 1,2-anhydrosugar and aryl boronic acid
- Author
-
Chen-Fu Liu, De-Cai Xiong, and Xin-Shan Ye
- Subjects
inorganic chemicals ,chemistry.chemical_classification ,Glycosylation ,010405 organic chemistry ,Aryl ,Organic Chemistry ,Glycoside ,010402 general chemistry ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Reagent ,Drug Discovery ,Organic chemistry ,Stereoselectivity ,Organic synthesis ,Boronic acid - Abstract
A new approach for the synthesis of phenolic glycosides via aromatic O-glycosylation of 1,2-anhydrosugar and aryl boronic acids was disclosed. This method is characterized by the use of aryl boronic acid as the aryl source and produces phenolic glycosides in a stereoselective manner. This reaction provides an alternative approach to the synthesis of phenolic glycosides. It also represents a new application of aryl boronic acids as versatile reagents in organic synthesis.
- Published
- 2016
44. Redirecting Killer T Cells through Incorporation of Azido Sugars for Tethering Ligands
- Author
-
Demin Zhou, Chuanling Zhang, Weiling Wang, Qing Xia, Zhiying Zhao, Xin-Shan Ye, Ziwei Zhang, Sulong Xiao, and Lihe Zhang
- Subjects
0301 basic medicine ,Glycan ,Azides ,Time Factors ,Cell Survival ,Integrin ,010402 general chemistry ,Ligands ,01 natural sciences ,Biochemistry ,03 medical and health sciences ,Jurkat Cells ,Folic Acid ,Polysaccharides ,Cell Line, Tumor ,Cytotoxic T cell ,Humans ,IL-2 receptor ,Cytotoxicity ,Molecular Biology ,biology ,Dose-Response Relationship, Drug ,Organic Chemistry ,Rational design ,Natural killer T cell ,Chimeric antigen receptor ,0104 chemical sciences ,030104 developmental biology ,biology.protein ,Sialic Acids ,Molecular Medicine ,Immunotherapy ,Oligopeptides ,T-Lymphocytes, Cytotoxic - Abstract
The genetic expression of chimeric antigen receptors (CARs) on the surface of T cells enables the redirection of T-cell specificity. To broaden the versatility of T cells as tumor-specific killers, we developed a non-genetic approach by which azide-containing sialic acids were metabolically incorporated to modify cellular sialyl glycans. Given displaying such a chemical moiety on T cells, small molecular ligands such as RGD and folate, as proof-of-concept, instead of supersized antibodies were clicked orthogonally, leading to highly selective, time- and dose-dependent cytotoxicity to integrin αvβ3- and folate receptor-positive cells, respectively. This chemical approach provided a facile platform for rational design of cytotoxic T cells for targeted immunotherapy.
- Published
- 2017
45. Synthesis and Antigenic Evaluation of Oligosaccharide Mimics of Vi Antigen from Salmonella typhi
- Author
-
Lin Yang, Xin-Shan Ye, De-Cai Xiong, Meng-Man Wei, Jingjing Zhu, Gao-Lan Zhang, and Wanjun Yan
- Subjects
Stereochemistry ,Virulence ,Oligosaccharides ,Biocompatible Materials ,Alkenes ,010402 general chemistry ,Salmonella typhi ,01 natural sciences ,Chemical synthesis ,Typhoid fever ,Catalysis ,Antigen ,medicine ,Moiety ,chemistry.chemical_classification ,Cycloaddition Reaction ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Polysaccharides, Bacterial ,General Chemistry ,Oligosaccharide ,Triazoles ,HEXA ,medicine.disease ,0104 chemical sciences ,Biochemistry ,Dimerization ,Copper - Abstract
Salmonella typhi is responsible for typhoid fever, which is a serious health threat in developing countries. As a virulent factor of Salmonella typhi, the purified Vi polysaccharide (Vi PS) has become an effective vaccine to combat typhoid fever. The chemical synthesis can provide homogeneous and well-defined molecules for the development of Vi-based vaccines. However, the synthesis of Vi oligosaccharides in high yields and with exclusive α-stereoselectivities remains very challenging. In this paper, a series of Vi pseudooligosaccharides, including pseudo tetra-, hexa-, and octa-saccharides were efficiently synthesized. These oligosaccharide analogues were conjugated by carbon chain tether through olefin cross metathesis or by the 1,2,3-triazole moiety through copper (I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC). The binding affinities of these oligosaccharide mimics to anti-Vi antibodies were investigated. These results will be beneficial to the further development of Vi-based oligosaccharide vaccines.
- Published
- 2017
46. Correction: Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines
- Author
-
Chengcheng Song, Xin-Shan Ye, Xiu-Jing Zheng, Chang-Xin Huo, An Xiao, and Yue Gui
- Subjects
Chemistry ,Organic Chemistry ,Physical and Theoretical Chemistry ,Biochemistry ,Combinatorial chemistry ,MUC1 ,Glycopeptide ,Conjugate - Abstract
Correction for ‘Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines’ by An Xiao et al., Org. Biomol. Chem., 2016, 14, 7226–7237.
- Published
- 2017
47. 'Ring Opening–Ring Closure' Strategy for the Synthesis of Aryl-C-glycosides
- Author
-
De-Cai Xiong, Xin-Shan Ye, and Chen-Fu Liu
- Subjects
Molecular Structure ,Stereochemistry ,Aryl ,Potassium ,Monosaccharides ,Organic Chemistry ,Closure (topology) ,Regioselectivity ,chemistry.chemical_element ,Stereoisomerism ,Ring (chemistry) ,Medicinal chemistry ,chemistry.chemical_compound ,chemistry ,Cyclization ,Yield (chemistry) ,Stereoselectivity ,Glycosides ,Lewis acids and bases ,Lewis Acids - Abstract
A new "ring-opening-ring closure" strategy for the synthesis of aryl-C-glycosides was described. This strategy exploited the nickel-catalyzed regioselective β-O elimination of glycals by reactions with various aryl boronic acids or potassium aryltrifluoroborates to yield the ring-opened products, which underwent the Lewis acid, protonic acid, PhSeCl, or NBS mediated ring closure reactions to afford diverse aryl-C-glycosides. After Lewis acids and protonic acids were screened, it was found that, starting from the ring-opened substrates, the Ph3PHBr or Sc(OTf)3 mediated ring closure reaction provided α- or β-preferred aryl-C-Δ(2,3)-glycosides, respectively. Furthermore, β-D-phenyl-C-glycosides were successfully prepared via the PhSeCl-mediated cyclization reaction, whereas the α-D-phenyl-C-glycoside was obtained via the NBS-mediated cyclization reaction. After removal of the 2-substituted functionalities by Bu3SnH/AIBN, the synthesis of 2-deoxy-aryl-C-glycosides was ultimately realized in a stereoselective manner.
- Published
- 2014
48. N-Arylated-Lactam-Type Iminosugars as New Immunosuppressive Agents: Discovery, Optimization, and Biological Evaluation
- Author
-
Jingjing Zhu, De-Cai Xiong, Yuxin Cui, Chengcheng Song, Xin-Shan Ye, Xiaowei Wu, Yifa Zhou, and Fu-Yu Zhang
- Subjects
Lactams ,Stereochemistry ,Proton Magnetic Resonance Spectroscopy ,Drug Evaluation, Preclinical ,Iminosugar ,Biochemistry ,Jurkat cells ,Mass Spectrometry ,Coupling reaction ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,In vivo ,Drug Discovery ,Animals ,Monosaccharide ,IC50 ,Cell Proliferation ,chemistry.chemical_classification ,Organic Chemistry ,General Chemistry ,Combinatorial chemistry ,In vitro ,Imino Sugars ,chemistry ,Lactam ,Immunosuppressive Agents ,Spleen - Abstract
We have previously described the discovery of N-alkylated iminosugars that showed immunosuppressive activity both in vitro and in vivo. Herein, we report the synthesis and biological evaluation of N-arylated lactam-type iminosugar derivatives. The synthesis started from simple monosaccharides and featured a Buchwald-Hartwig coupling reaction to construct the key N-aryl connection, thereby providing a highly diverse compound library. Structure-activity relationship studies, guided by a mouse-spleen-proliferation assay, led to the identification of 'hit' compound 12 f. Subsequently, the systematic modification of compound 12 f afforded compounds 21 h, 21 k, 21 n, 21 t, and 21 x with improved activities (IC50 =12-30 μM) and low Jurkat cytotoxicities (IC50 >100 μM). These new compounds also inhibited the secretion of IFN-γ and IL-4, which are hallmark cytokines of Th1 and Th2 cells, respectively. This work demonstrated that the N-arylated iminosugar structure represents a new scaffold with immunosuppressive activity.
- Published
- 2014
49. Synthesis of 2-deoxy-C-glycosides via Lewis acid-mediated rearrangement of 2,3-anhydro-1-thiopyranosides
- Author
-
Wenming Li, Chao Gao, Qin Li, Xin-Shan Ye, De-Cai Xiong, and Yuan Wang
- Subjects
C glycosides ,chemistry.chemical_compound ,Stereospecificity ,Nucleophile ,Chemistry ,Stereochemistry ,Aryl ,Organic Chemistry ,Lewis acids and bases ,Phenols ,Coupling reaction - Abstract
An approach to the regio- and stereo-selective construction of 2-deoxy-C-glycosides via Lewis acid-mediated rearrangement of 2,3-anhydro-1-thiopyranosides is disclosed. Treatment of 2,3-anhydro-1-thiopyranosides with phenols in the presence of TMSOTf, the migration–O-glycosylation and Fries-like O to C rearrangement took place in succession, providing aryl 2-thio-2-deoxy-C-glycosides with the single thermodynamically favourable configuration (1C4 or 4C1) in good to excellent yields. The coupling reaction of 2,3-anhydro-1-thiopyranosides with trimethylsilylated or tributylstanylated nucleophiles in the presence of TMSOTf or Sc(OTf)3, via the migration–C-glycosylation process, afforded 2-thio-2-deoxy-C-glycosides in a stereospecific manner in moderate to good yields and with the C-1 and C-2 substituents opposite. The 2-thio-functionality was further removed to produce the corresponding 2-deoxy-C-glycosides. This method may provide a convenient route for the preparation of 2-deoxy-C-glycosides.
- Published
- 2014
50. ChemInform Abstract: 3-Butenyloxycarbonyl as a New Hydroxyl Protecting Group in Carbohydrate Synthesis
- Author
-
Nana Zeng, Xin-Shan Ye, and Youhong Niu
- Subjects
Chemistry ,Group (periodic table) ,fungi ,Carbohydrate synthesis ,food and beverages ,Organic chemistry ,General Medicine ,Protecting group - Abstract
The 3-butenyloxycarbonyl group can be introduced into carbohydrates such as (I) under mild conditions.
- Published
- 2016
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