- Synthesis, Optimization, and Evaluation of Glycosylated Naphthalimide Derivatives as Efficient and Selective Insect β- N-Acetylhexosaminidase OfHex1 Inhibitors
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Insect chitinolytic β-N-acetylhexosaminidase OfHex1, from the agricultural pest Ostrinia furnacalis (Guenée), is considered as a potential target for green pesticide design. In this study, rational molecular design and optimization led to the synthesis of compounds 15r (Ki = 5.3 μM) and 15y (Ki = 2.7 μM) that had superior activity against OfHex1 than previously reported lead compounds. Both compounds 15r and 15y had high selectivity toward OfHex1 over human β-N-acetylhexosaminidase B (HsHexB) and human O-GlcNAcase (hOGA). In addition, to investigate the basis for the potency of glycosylated naphthalimides against OfHex1, molecular docking and molecular dynamics simulations were performed to study possible binding modes. Furthermore, the in vivo biological activity of target compounds with efficient OfHex1 inhibitory potency was assayed against Myzus persicae, Plutella xylostella, and O. furnacalis. This present work indicates that glycosylated naphthalimides can be further developed as potential pest control and management agents targeting OfHex1.
- Shen, Shengqiang,Dong, Lili,Chen, Wei,Wu, Renjie,Lu, Huizhe,Yang, Qing,Zhang, Jianjun
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p. 6387 - 6396
(2019/06/07)
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- Discovery of Glycosylated Genipin Derivatives as Novel Antiviral, Insecticidal, and Fungicidal Agents
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A series of novel genipin glycoside derivatives incorporating 11 glycosidic moieties at either the 1 or 10 position of genipin were designed and synthesized. These compounds exhibited moderate to excellent inhibitory activities against tobacco mosaic virus. Especially, the in vitro and in vivo activities of compounds 6e, 7c, 7d, 7f, 7h, and 7i were comparable to that of ribavirin. In particular, compound 7c, the mannosyl derivative of genipin at the 10 position, showed the best activity. The series of genipin glycosyl derivatives also displayed fungicidal activities against 14 kinds of phytopathogenic fungi, especially for Rhizoctonia cerealis and Sclerotinia sclerotiorum. Moreover, compound 6h exhibited good insecticidal activity against diamondback moth; compounds 7b, 7c, and 7g exhibited moderate insecticidal activity against three kinds of Lepidoptera pests (oriental armyworm, cotton bollworm, and corn borer); and compound 7e showed excellent larvacidal activities against mosquito.
- Xia, Qing,Dong, Jianyang,Li, Ling,Wang, Qiang,Liu, Yuxiu,Wang, Qingmin
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p. 1341 - 1348
(2018/02/19)
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- Synthesis of cationic glucosamino nucleic acids for stabilizing oligonucleotides
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Glucosamino nucleic acids (GANAs) bearing a β-N-glycoside bond between carbon 1 of the glucosamine and the nucleobase nitrogen were synthesized and incorporated into oligonucleotides (4′,6′-GANA and 3′,6′-GANA). The thermal stability of oligonucleotide duplexes containing the GANA zwitterionic nucleotides was also investigated.
- Kitamura, Yoshiaki,Moribe, Shuichi,Kitade, Yukio
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supporting information
p. 3174 - 3176
(2018/10/08)
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- Differently N-protected 3,4,6-tri-O-acetyl-2-amino-2-deoxy-d-glucopyranosyl chlorides and their application in the synthesis of diosgenyl 2-amino-2-deoxy-β-d-glucopyranoside
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Four differently N-protected 3,4,6-tri-O-acetyl-2-amino-2-deoxy-d- glucopyranosyl chlorides were synthesized and used as glycosyl donors in reactions with diosgenin. The following amine group protections were tested: trifluoroacetyl (TFA), 2,2,2-trichloroethoxycarbonyl (Troc), phthaloyl (Phth), and tetrachlorophthaloyl (TCP). Products of glycosylation were deprotected to yield diosgenyl 2-amino-2-deoxy-β-d-glucopyranoside. The efficiency of the procedures is discussed. Additionally, a single-crystal X-ray diffraction analysis for 3,4,6-tri-O-acetyl-2-deoxy-2-tetrachlorophthalimido-β-d- glucopyranosyl chloride is reported. Orientations of the pyranose substituents as well as the planarity of the acetoxy and phthalimide groups in the crystal lattice are discussed. Structural evidence is presented for a mesomeric effect in both groups. The preference of the cis over trans orientation of the acetoxy group is confirmed in the crystal lattice.
- Bednarczyk, Dorota,Walczewska, Agata,Grzywacz, Daria,Sikorski, Artur,Liberek, Beata,Myszka, Henryk
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- Probing synergy between two catalytic strategies in the glycoside hydrolase O-GlcNAcase using multiple linear free energy relationships
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Human O-GlcNAcase plays an important role in regulating the post-translational modification of serine and threonine residues with β-O-linked N-acetylglucosamine monosaccharide unit (O-GlcNAc). The mechanism of O-GlcNAcase involves nucleophilic participation of the 2-acetamido group of the substrate to displace a glycosidically linked leaving group. The tolerance of this enzyme for variation in substrate structure has enabled us to characterize O-GlcNAcase transition states using several series of substrates to generate multiple simultaneous free-energy relationships. Patterns revealing changes in mechanism, transition state, and rate-determining step upon concomitant variation of both nucleophilic strength and leaving group abilities are observed. The observed changes in mechanism reflect the roles played by the enzymic general acid and the catalytic nucleophile. Significantly, these results illustrate how the enzyme synergistically harnesses both modes of catalysis; a feature that eludes many small molecule models of catalysis. These studies also suggest the kinetic significance of an oxocarbenium ion intermediate in the O-GlcNAcase-catalyzed hydrolysis of glucosaminides, probing the limits of what may be learned using nonatomistic investigations of enzymic transition-state structure and offering general insights into how the superfamily of retaining glycoside hydrolases act as efficient catalysts.
- Greig, Ian R.,Macauley, Matthew S.,Williams, Ian H.,Vocadlo, David J.
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supporting information; experimental part
p. 13415 - 13422
(2010/01/16)
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- SELECTIVE GLYCOSIDASE INHIBITORS AND USES THEREOF
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The invention provides compounds of formula (I) for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds The invention also provides methods of treating diseas
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Page/Page column 56
(2008/06/13)
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- Synthesis and induction of apoptosis in B cell chronic leukemia by diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside hydrochloride and its derivatives
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2-Acetamido-2-deoxy-D-glucose hydrochloride (D-glucosamine hydrochloride) has been used for the preparation of 1,3,4,6-tetra-O-acetyl-2-deoxy-2-trifluoroacetamido-β- (4) and 2-tetrachlorophthalimido-α,β-D-glucopyranose (6), which have been transformed into the appropriate bromides and the chloride. Both bromo and chloro sugars were used as a glycosyl donors for the glycosylation of diosgenin [(25R)-spirost-5-en-3β-ol]. These condensations were conducted under mild conditions, using silver triflate as a promoter, and gave diosgenyl glycosides 9 and 12. Each of them was converted into diosgenyl 2-amino-2-deoxy-β-D-glucopyranoside hydrochloride (11) and N-acylamido derivatives. The structures of all new glycosides were established by 1H and 13C NMR spectroscopy. These diosgenyl glycosides are the first saponins containing the D-glucosamine residue that have been synthesized. These compounds show promising antitumor activities. The synthetic saponins increase the number of apoptotic B cells, in combination with cladribine (2-CdA), that are isolated from chronic lymphotic leukemia (B-CLL) patients.
- Myszka, Henryk,Bednarczyk, Dorota,Najder, Maria,Kaca, Wiesllaw
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p. 133 - 141
(2007/10/03)
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- Stereospecific solution- and solid-phase glycosylations. Synthesis of β-linked saccharides and construction of disaccharide libraries using phenylsulfenyl 2-deoxy-2-trifluoroacetamido glycopyranosides as glycosyl donors
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An efficient strategy to construct β-O-2-amino-2-deoxyglycopyranosidic linkages using glycosyl sulfoxides is demonstrated. Phenylsulfenyl 2-deoxy- 2-trifluoroacetamido glycopyranosides were found to be reactive glycosyl donors in both solid- and solution-phase glycosylations, affording the corresponding β-glycosides exclusively and in high yield. The trifluoroacetamido group was removed under mild conditions, allowing orthogonal derivatization of multiple protected amino groups on an oligosaccharide or glycoconjugate. On the basis of the results with these glycosyl donors, a solid-phase β-linked disaccharide library was constructed. The scope and flexibility of this approach will be discussed.
- Silva, Domingos J.,Wang, Huiming,Allanson, Nigel M.,Jain, Rakesh K.,Sofia, Michael J.
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p. 5926 - 5929
(2007/10/03)
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- Synthesis of a 3-ether analogue of lipid A
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Lipid A 3-ether analogues were synthesized from allyl 2-deoxy-4,6-O-isopropylidene-2-trifluoroacetamido-α-D-glucopyranoside and 3,4,6-tri-O-acetyl-2-trifluoroacetamido-α-D-glucopyranosyl bromide.The compound lost completely the endotoxic activity.
- Shiozaki, Masao,Kobayashi, Yoshiyuki,Arai, Masami,Ishida, Noboru,Hiraoka, Tetsuo,et al.
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