- Preparation of new β-D-xyloside- and β-D-xylobioside-based ionic liquids through chemical and/or enzymatic reactions
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Several tetraalkylphosphonium and tetraalkylammonium salts containing xyloside- and xylobioside-based anionic moieties have been prepared. Two stereoselective routes have been developed: i) a chemical pathway in four steps from D-xylose, and ii) a chemoenzymatic pathway directly from biomass-derived xylans. These salts displayed interesting properties as ionic liquids. Their structures have been correlated to their thermal properties (melting, glass transition and decomposition temperatures).
- Gatard,Plantier-Royon,Rémond,Muzard,Kowandy,Bouquillon
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Read Online
- The search for new amphiphiles: Synthesis of a modular, high-throughput library
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Amphiphilic compounds are used in a variety of applications due to their lyotropic liquid-crystalline phase formation, however only a limited number of compounds, in a potentially limitless field, are currently in use. A library of organic amphiphilic compounds was synthesised consisting of glucose, galactose, lactose, xylose and mannose head groups and double and triple-chain hydrophobic tails. A modular, high-throughput approach was developed, whereby head and tail components were conjugated using the coppercatalysed azide-alkyne cycloaddition (CuAAC) reaction. The tails were synthesised from two core alkyne-tethered intermediates, which were subsequently functionalised with hydrocarbon chains varying in length and degree of unsaturation and branching, while the five sugar head groups were selected with ranging substitution patterns and anomeric linkages. A library of 80 amphiphiles was subsequently produced, using a 24-vial array, with the majority formed in very good to excellent yields. A preliminary assessment of the liquid-crystalline phase behaviour is also presented
- Feast, George C.,Lepitre, Thomas,Mulet, Xavier,Conn, Charlotte E.,Hutt, Oliver E.,Savage, G. Paul,Drummond, Calum J.
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- Synthesis, surface properties, and biocompatibility of 1,2,3-triazole- containing alkyl β-D-xylopyranoside surfactants
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We are interested in the development of surfactants derived from hemicellulosic biomass, as they are potential components in pharmaceuticals, personal care products, and other detergents. Such surfactants should exhibit low toxicity in mammalian cells. In this study we synthesized a series of alkyl or fluoroalkyl β-xylopyranosides from azides and an alkyne using the copper-catalyzed azide-alkyne (CuAAC) 'click' reaction in 4 steps from xylose. The purified products were evaluated for both their surfactant properties, and for their biocompatibility. Unlike other carbohydrate-based surfactants, liquid-crystalline behavior was not observed by differential scanning calorimetry. The triazole-containing β-xylopyranosides with short (6 carbons) and long (>12 carbons) chains exhibited no toxicity at concentrations ranging from 1 to 1000 μM. Triazole-containing β-xylopyranosides with 8, 10, or 12 carbons caused toxicity via apoptosis, with CC50 values ranging from 26-890 μM. The two longest chain compounds did form stable monolayers at the air-water interface over a range of temperatures, although a brief transition to an the unstable monolayer was observed.
- Davis Oldham,Seelam, Srivenu,Lema, Carolina,Aguilera, Renato J.,Fiegel, Jennifer,Rankin, Stephen E.,Knutson, Barbara L.,Lehmler, Hans-Joachim
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- Design, Synthesis, biological investigations and molecular interactions of triazole linked tacrine glycoconjugates as Acetylcholinesterase inhibitors with reduced hepatotoxicity
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Tacrine is a known Acetylcholinesterase (AChE) inhibitors having hepatotoxicity as main liability associated with it. The present study aims to reduce its hepatotoxicity by synthesizing tacrine linked triazole glycoconjugates via Huisgen's [3 + 2] cycloaddition of anomeric azides and terminal acetylenes derived from tacrine. A series of triazole based glycoconjugates containing both acetylated (A-1 to A-7) and free sugar hydroxyl groups (A-8 to A-14) at the amino position of tacrine were synthesized in good yield taking aid from molecular docking studies and evaluated for their in vitro AChE inhibition activity as well as hepatotoxicity. All the hybrids were found to be non-toxic on HePG2 cell line at 200 μM (100 % cell viability) as compared to tacrine (35 % cell viability) after 24 h of incubation period. Enzyme kinetic studies carried out for one of the potent hybrids in the series A-1 (IC50 0.4 μM) revealed its mixed inhibition approach. Thus, compound A-1 can be used as principle template to further explore the mechanism of action of different targets involved in Alzheimer's disease (AD) which stands as an adequate chemical probe to be launched in an AD drug discovery program.
- Ahmed, Ajaz,Bhagat, Kavita,Choudhary, Sushil,Kaur Gulati, Harmandeep,Kumar, Ajay,Kumar, Nitish,Mukherjee, Debaraj,Singh Bedi, Preet Mohinder,Singh, Atamjit,Singh, Harbinder,Vir Singh, Jatinder
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- Synthesis and biological evaluation of 3β-O-neoglycosides of caudatin and its analogues as potential anticancer agents
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In order to study the structure–activity relationship (SAR) of C21-steroidal glycosides toward human cancer cell lines and explore more potential anticancer agents, a series of 3β-O-neoglycosides of caudatin and its analogues were synthesized. The results revealed that most of peracetylated 3β-O-monoglycosides demonstrated moderate to significant antiproliferative activities against four human cancer cell lines (MCF-7, HCT-116, HeLa, and HepG2). Among them, 3β-O-(2,3,4-tri-O-acetyl-β-L-glucopyranosyl)-caudatin (2k) exhibited the highest antiproliferative activity aganist HepG2 cells with an IC50 value of 3.11 μM. Mechanical studies showed that compound 2k induced both apoptosis and cell cycle arrest at S phase in a dose dependent manner. Overall, these present findings suggested that glycosylation is a promising scaffold to improve anticancer activity for naturally occurring C21-steroidal aglycones, and compound 2k represents a potential anticancer agent deserved further investigation.
- Li, Xiao-San,Chen, Tang-Ji,Xu, Zhi-Peng,Long, Juan,He, Miao-Ying,Zhan, He-Hui,Zhuang, Hai-Cai,Wang, Qi-Lin,Liu, Li,Yang, Xue-Mei,Tang, Jin-Shan
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- Synthesis of podophyllotoxin-glycosyl triazoles via click protocol mediated by silver (I)-N-heterocyclic carbenes and their anticancer evaluation as topoisomerase-II inhibitors
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Herein we report the regioselective synthesis of podophyllotoxin-Glycosyl triazole hybrids catalysed by Ag(I)-N-heterocyclic carbene (Ag(I)-NHC) in a short reaction time (～30 min) at ambient conditions. In principle, it is the first report of Click alkyne-azide cycloaddition catalysed by Ag(I)-NHC catalyst and moreover, this new methodology yielded good results when compared with traditional CuAAC in terms of reaction time and selectivity. The synthesised compounds were further explored for in vitro anticancer activity against four human cancer cell lines Du145, HeLa, A-549, and MCF-7 and found that these synthesised compounds possess significant anticancer activity. Further, the compounds 5a and 5e were identified as promising leads due to their better activity across all cell lines than that of the standard drug etoposide. Molecular docking studies of 5a & 5e with DNA Topoisomerase-II were revealed that the free energy calculations of active compounds were in good agreement with observed IC50 values.
- Nerella, Srinivas,Kankala, Shravankumar,Gavaji, Brahmeshwari
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supporting information
p. 9 - 16
(2019/06/27)
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- Total Synthesis of (+)-Erogorgiaene and the Pseudopterosin A?F Aglycone via Enantioselective Cobalt-Catalyzed Hydrovinylation
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Due to their pronounced bioactivity and limited availability from natural resources, metabolites of the soft coral Pseudopterogorgia elisabethae, such as erogorgiaene and the pseudopterosines, represent important target molecules for chemical synthesis. We have now developed a particularly short and efficient route towards these marine diterpenes exploiting an operationally convenient enantioselective cobalt-catalyzed hydrovinylation as the chirogenic step. Other noteworthy C?C bond forming transformations include diastereoselective Lewis acid-mediated cyclizations, a Suzuki coupling and a carbonyl ene reaction. Starting from 4-methyl-styrene the anti-tubercular agent (+)-erogorgiaene (>98 % ee) was prepared in only 7 steps with 46 % overall yield. In addition, the synthesis of the pseudopterosin A aglycone was achieved in 12 steps with 30 % overall yield and, surprisingly, was found to exhibit a similar anti-inflammatory activity (inhibition of LPS-induced NF-κB activation) as a natural mixture of pseudopterosins A?D or iso-pseudopterosin A, prepared by β-D-xylosylation of the synthetic aglycone.
- Movahhed, Sohajl,Westphal, Julia,Kempa, Alexander,Schumacher, Christian Eric,Sperlich, Julia,Neud?rfl, J?rg-Martin,Teusch, Nicole,Hochgürtel, Matthias,Schmalz, Hans-Günther
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supporting information
p. 11574 - 11579
(2021/07/02)
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- Protecting carbohydrates with ethers, acetals and orthoesters under basic conditions
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Chlorinated ethyl and vinyl ethers are introduced at various positions of carbohydrates. Depending on the relative stereochemistry, vinylethers, acetals or orthoesters are formed under basic conditions. The products are stable, but are easily deprotected
- Liang, Yang,Pedersen, Christian M.
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supporting information
p. 7598 - 7601
(2021/09/22)
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- Isolation and characterization of triterpenoid saponins from leaves of Aralia nudicaulis L
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Three new oleanolic glycosides (1–3), along with seven known saponins from various plants (4–10) were isolated for the first time from the leaves of Aralia nudicaulis. Their structures were elucidated on the basis of spectroscopic evidence, including 1D and 2D NMR, and HRESIMS. Nudicauloside A and B (1–2) have shown moderate anti-inflammatory activity, as demonstrated by inhibition of LPS-induced NO production in raw 264.7 murine macrophages (IC50 = 74–101 μM).
- Lavoie, Serge,Pierra, Julie,Legault, Jean,Raminoson, Diamondra,Lion, Quentin,Mshvildadze, Vakhtang,Pichette, André
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p. 184 - 189
(2021/04/23)
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- ACYLATED ACTIVE AGENTS AND METHODS OF THEIR USE FOR THE TREATMENT OF METABOLIC DISORDERS AND NONALCOHOLIC FATTY LIVER DISEASE
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Disclosed herein are acylated active agents, compositions containing them, unit dosage forms containing them, and methods of their use, e.g., for treating a metabolic disorder or nonalcoholic fatty liver disease or for modulating a metabolic marker or non
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(2021/06/11)
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- ACYLATED ACTIVE AGENTS AND METHODS OF THEIR USE FOR THE TREATMENT OF METABOLIC DISORDERS AND NONALCOHOLIC FATTY LIVER DISEASE
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Disclosed herein are acylated active agents (e.g., acylated hydroxybenzoic acid), compositions containing them, unit dosage forms containing them, and methods of their use, e.g., for treating a metabolic disorder or nonalcoholic fatty liver disease or for
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Page/Page column 34
(2021/06/11)
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- Design, synthesis and biological evaluation of carbohydrate-based sulphonamide derivatives as topical antiglaucoma agents through selective inhibition of carbonic anhydrase II
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A series of new carbohydrate-based sulphonamide derivatives were designed, synthesised by employing the so-call ‘sugar-tail’ approach. The compounds were evaluated in vitro against a panel of CAs. Compared to their parent compound p-sulfamoylbenzoic acid, these compounds showed nearly 100-fold improvement in their binding affinities against hCA II in vitro. All of compounds showed great water solubility and the pH value of their water solutions of compounds is 7.0. Such properties are advantageous to make them much less irritating to the eye when applied topical glaucomatous drugs, compared to the relatively highly acidic dorzolamide preparations (pH 5.5). Notably, compounds 7d, 7 g, 7 h demonstrated to topically lower intraocular pressure (IOP) in glaucomatous animals better than brinzolamide when applied as a 1% solution directly into the eye. Low cytotoxicity on human cornea epithelial cell was observed in the tested concentrations by the MTT assay.
- Fan, Zhanfang,Guo, Chun,Hou, Zhuang,Li, Chuanchao,Lin, Bin,Liu, Yang,Liu, Yichuang,Wang, Yitong,Zhang, Miao
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p. 383 - 390
(2019/12/30)
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- Non-naturally Occurring Regio Isomer of Lysophosphatidylserine Exhibits Potent Agonistic Activity toward G Protein-Coupled Receptors
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Lysophosphatidylserine (LysoPS), an endogenous ligand of G protein-coupled receptors, consists of l-serine, glycerol, and fatty acid moieties connected by phosphodiester and ester linkages, respectively. An ester linkage of phosphatidylserine can be hydrolyzed at the 1-position or at the 2-position to give 2-acyl lysophospholipid or 1-acyl lysophospholipid, respectively. 2-Acyl lysophospholipid is in nonenzymatic equilibrium with 1-acyl lysophospholipid in vivo. On the other hand, 3-acyl lysophospholipid is not found, at least in mammals, raising the question of whether the reason for this might be that the 3-acyl isomer lacks the biological activities of the other isomers. Here, to test this idea, we designed and synthesized a series of new 3-acyl lysophospholipids. Structure-activity relationship studies of more than 100 "glycol surrogate"derivatives led to the identification of potent and selective agonists for LysoPS receptors GPR34 and P2Y10. Thus, the non-natural 3-acyl compounds are indeed active and appear to be biologically orthogonal with respect to the physiologically relevant 1-and 2-acyl lysophospholipids.
- Nakamura, Sho,Sayama, Misa,Uwamizu, Akiharu,Jung, Sejin,Ikubo, Masaya,Otani, Yuko,Kano, Kuniyuki,Omi, Jumpei,Inoue, Asuka,Aoki, Junken,Ohwada, Tomohiko
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p. 9990 - 10029
(2020/10/18)
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- Studies on the stereoselective synthesis and immunosuppressive activity of dihydroartemisinin-O-glycoside derivatives
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Eight new dihydroartemisinin-O-glycosides were synthesized with their relative configurations were determined based on NMR spectrum. In vitro immunosuppressive assay showed that 10α-dihydroartemisinin-β-O-D-mannoside (19a) demonstrate 88percent inhibition towards T cells proliferation and 98percent reduction in IFN-γ levels in cell media. These results suggest that dihydroartemisinin-O-glycoside as a potential lead for further in vivo evaluation.
- Bian, Hongzhu,Dong, Xun,Shen, Zhengwu,Xu, Wei,Yu, Jingfeng,Yu, Yu,Zhang, Jinghua,Zou, Xiaosu
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supporting information
(2020/07/21)
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- Synthesis of xylal- and arabinal-based crown ethers and their application as asymmetric phase transfer catalysts
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New xylal- and arabinal-based monoaza-15-crown-5 ethers were synthesized starting from l- and d-xylose, and l- and d-arabinose, respectively. These monosaccharide-based chiral macrocycles were tested as phase transfer catalysts in a few asymmetric reactions. The xylal-based crown compounds proved to be efficient catalysts in a few liquid-liquid phase reactions. The epoxidation of trans-chalcone and the Darzens condensation of α-chloroacetophenone with benzaldehyde took place with complete diastereoselectivity and up to 77% ee and 58% ee, respectively. It was found that the substituents in the aromatic ring of the chalcone and the α-chloroacetophenone had an influence on the enantioselectivity. The highest ee values were obtained in the epoxidation of 4-chlorochalcone (81% ee) and in the reaction of a 2-naphthyl analogue (96% ee), while in the Darzens condensation of 4-phenyl-α-chloroacetophenone with benzaldehyde, a maximum ee of 91% was detected. The configuration of the monosaccharide unit in the crown ring influenced the absolute configuration of the epoxyketones synthesized.
- Nemcsok, Tamás,Rapi, Zsolt,Bagi, Péter,Keglevich, Gy?rgy,Bakó, Péter
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p. 107 - 119
(2019/11/16)
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- Propargyl-containing xylose and synthesis method thereof
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The invention discloses propargyl-containing xylose and a preparation method thereof. The method comprises the following steps: using D-xylose as a raw material, carrying out full acetyl protection onthe D-xylose, introducing p-nitrophenoxy into a first position of an obtained compound, and removing acetyl to obtain a compound A; introducing tert-butyl dimethyl into the position 2, the position 3or the position 4 of the obtained compound A to obtain a compound B, a compound C and a compound D, and separating the compound B, the compound C and the compound D; and respectively carrying out acetyl protection on hydroxyl groups of the compound B, the compound C and the compound D, then removing the tert-butyl dimethyl, and respectively introducing propargyl into the position 2, the position3 and the position 4 to obtain the propargyl-containing xylose. According to the method disclosed by the invention, the propargyl is selectively connected to xylose for the first time by using a method for carrying out occupying by using tert-butyl dimethyl (TBS), so that a platform is provided for subsequent connection of the xylose to protein or amino acid, and a foundation is laid for biological research in the future.
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Paragraph 0035-0038
(2020/07/28)
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- BIARYL AMIDES WITH MODIFIED SUGAR GROUPS FOR TREATMENT OF DISEASES ASSOCIATED WITH HEAT SHOCK PROTEIN PATHWAY
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Provided are biaryl amides and coumarin-based compounds with modified sugar groups for treatment of diseases associated with heat shock protein pathway. The compounds having the following formulas, wherein variables are as defined herein. Formulae (I), (II), (III), (IV), and (V), Pharmaceutical compositions of the compounds are also provided. These biaryl amides and coumarin-based derivatives with modified sugar groups are useful for treatment and prevention of diseases and disorders, including neurological disorders, such as neurodegenerative diseases and nerve damaging disorders, for example, diabetic peripheral neuropathy.
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Page/Page column 174; 246
(2019/12/04)
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- S-Adamantyl Group Directed Site-Selective Acylation: Applications in Streamlined Assembly of Oligosaccharides
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The site-selective functionalization of carbohydrates is an active area of research. Reported here is the surprising observation that the sterically encumbered adamantyl group directed site-selective acylation at the C2 position of S-glycosides through dispersion interactions between the adamantyl C?H bonds and the π system of the cationic acylated catalyst, which may have broad implications in many other chemical reactions. Because of their stability, chemical orthogonality, and ease of activation for glycosylation, the site-selective acylation of S-glycosides streamlines oligosaccharide synthesis and will have wide applications in complex carbohydrate synthesis.
- Blaszczyk, Stephanie A.,Xiao, Guozhi,Wen, Peng,Hao, Hua,Wu, Jessica,Wang, Bo,Carattino, Francisco,Li, Ziyuan,Glazier, Daniel A.,McCarty, Bethany J.,Liu, Peng,Tang, Weiping
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supporting information
p. 9542 - 9546
(2019/06/10)
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- Design, synthesis of oleanolic acid-saccharide conjugates using click chemistry methodology and study of their anti-influenza activity
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The development of entry inhibitors is an emerging approach to the inhibition of influenza virus. In our previous research, oleanolic acid (OA) was discovered as a mild influenza hemagglutinin (HA) inhibitor. Herein, as a further study, we report the preparation of a series of OA-saccharide conjugates via the CuAAC reaction, and the anti-influenza activity of these compounds was evaluated in vitro. Among them, compound 11b, an OA-glucose conjugate, showed a significantly increased anti-influenza activity with an IC50 of 5.47 μM, and no obvious cytotoxic effect on MDCK cells was observed at 100 μM. Hemagglutination inhibition assay and docking experiment indicated that 11b might interfere with influenza virus infection by acting on HA protein. Broad-spectrum anti-influenza experiments showed 11b to be robustly potent against 5 different strains, including influenza A and B viruses, with IC50 values at the low-micromole level. Overall, this finding further extends the utility of OA-saccharide conjugates in anti-influenza virus drug design.
- Su, Yangqing,Meng, Lingkuan,Sun, Jiaqi,Li, Weijia,Shao, Liang,Chen, Kexuan,Zhou, Demin,Yang, Fan,Yu, Fei
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- Monosaccharide Analogues of Anticancer Peptide R-Lycosin-I: Role of Monosaccharide Conjugation in Complexation and the Potential of Lung Cancer Targeting and Therapy
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Glycoconjugation is a promising modification strategy for the optimization of peptide drugs. In this study, five different monosaccharide derivatives (7a-e) were covalently linked to the N-terminal of R-lycosin-I, which yielded five glycopeptides (8a-e). They demonstrated increased or reduced cytotoxicity depending on monosaccharide types, which might be explained by the changes of physicochemical properties. Among all synthesized glycopeptides, only 8a exhibited increased cytotoxicity (IC50 = 9.6 ± 0.3 μM) and selectivity (IC50 = 37.4 ± 5.9 μM). The glucose transporter 1 (GLUT1) with high expression in cancer cells was approved to be involved in the cytotoxicity and selectivity enhancement of 8a. Furthermore, 8a but not R-lycosin-I inhibited tumor growth in the nude mice xenograft model without generating side effects intraperitoneally. Taken together, this study reveals the different monosaccharide roles in peptide modification and also provides an optimized anticancer peptide with high activity and selectivity, that is, 8a might be a promising lead for developing anticancer drugs.
- Zhang, Peng,Ma, Jing,Zhang, Qianqian,Jian, Shandong,Sun, Xiaoliang,Liu, Bobo,Nie, Liqin,Liu, Meiyan,Liang, Songping,Zeng, Youlin,Liu, Zhonghua
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p. 7857 - 7873
(2019/10/11)
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- Phosphotungstic acid as a novel acidic catalyst for carbohydrate protection and glycosylation
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This work demonstrates the utilization of phosphotungstic acid (PTA) as a novel acidic catalyst for carbohydrate reactions, such as per-O-acetylation, regioselective O-4,6 benzylidene acetal formation, regioselective O-4 ring-opening, and glycosylation. These reactions are basic and salient during the synthesis of carbohydrate-based bioactive oligomers. Phosphotungstic acid's high acidity and eco-friendly character make it a tempting alternative to corrosive homogeneous acids. The various homogenous acid catalysts were replaced by the phosphotungstic acid solely for different carbohydrate reactions. It can be widely used as a catalyst for organic reactions as it is thermally stable and easy to handle. In our work, the reactions are operated smoothly under ambient conditions; the temperature varies from 0 °C to room temperature. Good to excellent yields were obtained in all four kinds of reactions.
- Chen, Jyun-Siao,Sankar, Arumugam,Lin, Yi-Jyun,Huang, Po-Hsun,Liao, Chih-Hsiang,Wu, Shen-Shen,Wu, Hsin-Ru,Luo, Shun-Yuan
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p. 33853 - 33862
(2019/11/11)
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- Xylose derivatives and process for preparation thereof
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Disclosure of the present invention relates to a method for synthesis of a xylose derivative, which comprises protecting a xylose with a protective group, followed by incorporating to a halogen atom as a leaving group; removing the protective groups and using water-soluble ligands to carry out a Suzuki cross-couplings reaction with a palladium catalyst in a water solution. Ten new xylose derivatives as obtained by the method are also provided.
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Page/Page column 7; 15
(2019/09/01)
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- Design, synthesis and molecular docking analysis of flavonoid derivatives as potential telomerase inhibitors
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Based on the structural scaffolds of natural products, two series of flavonoid derivatives, for a total of twelve compounds, were designed and synthesized as potential human telomerase inhibitors. Using a modified TRAP-PCR assay, compound 5c exhibited the most potent inhibitory activity against human telomerase with an IC50 value of less than 50 μM. In vitro, the results demonstrated that compound 5c had potent anticancer activity against five classes of tumor cell lines. The molecular docking and molecular dynamics analyses binding to the human telomerase holoenzyme were performed to elucidate the binding mode of active compound 5c. This finding helps the rational design of more potent telomerase inhibitors based on the structural scaffolds of natural products.
- Cheng, Mao-Sheng,Fan, Zhan-Fang,Fu, Ya,Ho, Sai-Tim,Hu, Chun,Liu, Yang,Shaw, Pang-Chui,Wang, Jian,Wen, Rui,Zhang, Lei
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- MULTIBIOTIC AGENTS AND METHODS OF USING THE SAME
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Multibiotic agents are disclosed. The multibiotic agents may contain two or more moieties linked through bonds cleavable in vivo. The bonds cleavable in vivo can be ester bonds, amide bonds, azo bonds, glycosidic bonds, carbonate linkers, or carbamate linkers. The moieties can be alcohol cores, amine cores, and/or acyls. Also disclosed are compositions containing multibiotic agents and methods of using the multibiotic agents.
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Page/Page column 137; 138
(2019/01/06)
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- Synthesis of C3-Neoglycosides of digoxigenin and their anticancer activities
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Cardiac glycosides exhibit significant anticancer effects and the glycosyl substitution at C3 position of digoxigenin is pivotal for their biological activity. In order to study the structure-activity relationship (SAR) of cardiac glycosides toward cancers and explore more potent anticancer agents, a series of C3-O-neoglycosides and C3-MeON-neoglycosides of digoxigenin were synthesized by the Koenigs-Knorr and neoglycosylation method, respectively. In addition, digoxigenin bisdigitoxoside and monodigitoxoside were prepared from digoxin by sodium periodate (NaIO4) oxidation and 6-aminocaproic acid hydrolysis. The SAR analysis revealed that C3-O-neoglycosides of digoxigenin exhibited stronger cytotoxicity and induction of Nur77 expression of tumor cells than C3-MeON-neoglycosides. Also, 3β-O-glycosides exhibited stronger anticancer effects than 3α-O-glycosides. Among them, 3β-O-(β-L-fucopyranosyl)-digoxigenin (3i) showed the highest activity on induction of Nur77 expression and translocation from the nucleus to cytoplasm, leading to cancer cell apoptosis.
- Li, Xiao-san,Ren, Yi-chang,Bao, Yu-zhou,Liu, Jie,Zhang, Xiao-kun,Zhang, You-wei,Sun, Xue-Long,Yao, Xin-sheng,Tang, Jin-Shan
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supporting information
p. 252 - 262
(2018/01/12)
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- ANTICANCER COMPOUNDS
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The present invention discloses compounds for inhibition of uncontrolled cell proliferation particularly in cancer stem cells. Particularly, the invention relates to compounds of Formula III to XIV for the treatment of cancer, such as breast and prostate cancer.
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Page/Page column 58; 59
(2018/11/22)
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- Aglycone Ebselen and β- D -Xyloside Primed Glycosaminoglycans Co-contribute to Ebselen β- D -Xyloside-Induced Cytotoxicity
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Most β-d-xylosides with hydrophobic aglycones are nontoxic primers for glycosaminoglycan assembly in animal cells. However, when Ebselen was conjugated to d-xylose, d-glucose, d-galactose, and d-lactose (8A-D), only Ebselen β-d-xyloside (8A) showed significant cytotoxicity in human cancer cells. The following facts indicated that the aglycone Ebselen and β-d-xyloside primed glycosaminoglycans co-contributed to the observed cytotoxicity: 1. Ebselen induced S phase cell cycle arrest, whereas 8A induced G2/M cell cycle arrest; 2. 8A augmented early and late phase cancer cell apoptosis significantly compared to that of Ebselen and 8B-D; 3. Both 8A and phenyl-β-d-xyloside primed glycosaminoglycans with similar disaccharide compositions in CHO-pgsA745 cells; 4. Glycosaminoglycans could be detected inside of cells only when treated with 8A, indicating Ebselen contributed to the unique property of intracellular localization of the primed glycosaminoglycans. Thus, 8A represents a lead compound for the development of novel antitumor strategy by targeting glycosaminoglycans.
- Tang, Yang,Zhang, Siqi,Chang, Yajing,Fan, Dacheng,Agostini, Ariane De,Zhang, Lijuan,Jiang, Tao
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p. 2937 - 2948
(2018/04/23)
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- THERAPEUTIC COMPOUNDS
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The invention provides compounds of formula (I): and salts thereof, wherein R1, R2, R3, B, X, Y, and Z have any of the values defined herein. The invention also provides pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, processes for preparing compounds of formula (I) and salts thereof, intermediates useful for preparing compounds of formula (I) and salts thereof, and therapeutic methods for treating cancer using a compound of formula (I) or a pharmaceutically acceptable salt thereof.
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Page/Page column 20; 21
(2017/06/30)
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- Synthetic transformations of higher terpenoids: XXXVI. Synthesis of furanolabdanoid glycoconjugates with a 1,2,3-triazole linker
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Procedures have been developed for the synthesis of 16-[(propargyloxy)methyl]- and 7- and 18-(propargyloxy)labda-8(9),13,14-trienes from phlomisoic acid. Copper-catalyzed cycloaddition of the labdanoid alkynes to azido derivatives of α-D-glucose, D-galactose, D-xylose, and L-arabinose afforded the corresponding N-glycosyl-1,2,3-triazole conjugates.
- Kremenko,Kharitonov, Yu. V.,Shul’ts
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- Synthesis of β-D-xylopyranoside thiophosphate derivatives
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A method of synthesis of β-D-xylopyranoside thiophosphate derivatives was developed. Biological testing revealed a high insecticidal activity in the synthesized compounds.
- Belakhov,Garabadzhiu,Boikova,Antonova
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p. 456 - 462
(2017/05/01)
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- Sequential Dy(OTf)3-Catalyzed Solvent-Free Per-O-Acetylation and Regioselective Anomeric De-O-Acetylation of Carbohydrates
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Dysprosium(III) trifluoromethanesulfonate-catalyzed per-O-acetylation and regioselective anomeric de-O-acetylation of carbohydrates can be tuned by adjusting the reaction medium. In this study, the per-O-acetylation of unprotected sugars by using a near-stoichiometric amount of acetic anhydride under solvent-free conditions resulted in the exclusive formation of acetylated saccharides as anomeric mixtures, whereas anomeric de-O-acetylation in methanol resulted in a moderate-to-excellent yield. Reactions with various unprotected monosaccharides or disaccharides followed by a semi-one-pot sequential conversion into the corresponding acetylated glycosyl hemiacetal also resulted in high yields. Furthermore, the obtained hemiacetals could be successfully transformed into trichloroimidates after Dy(OTf)3-catalyzed glycosylation.
- Yan, Yi-Ling,Guo, Jiun-Rung,Liang, Chien-Fu
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p. 2471 - 2479
(2017/09/06)
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- Stereoselective acetylation of hemicellulosic C5-sugars
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The stereoselective peracetylation of α-D-xylose (1) and α-L-arabinose (4) using a combination of triethylamine and acetic anhydride in the presence or absence of a catalytic amount of dimethylaminopyridine (DMAP) is described. The peracetylated D-xylose and L-arabinose alpha pyranose anomers 2α and 5α are obtained in 97% and 56% yields respectively. The peracetylated D-xylose beta pyranose anomer 2β is obtained in 71% yield through simple modification of the reaction conditions. Details regarding synthesis and isolation optimization studies under different conditions are presented below. The stereoselective peracetylation reactions disclosed here have been used to separate mixtures of D-xylose and L-arabinose as their peracetylated derivatives 2β and 5α in 47% and 42% yields and can provide pure pentoses after deacetylation.
- Herde, Zachary D.,John, Prathap D.,Alvarez-Fonseca, Dania,Satyavolu, Jagannadh,Burns, Christopher T.
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- Novel 1,2-cis-xyloside surfactant
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The invention discloses a novel xylose-derived 1,2-cis glycoside surfactant and application thereof. 1,2-cis alkoxy ethyl-alpha-D-pyranxyloside is obtained from D-xylose through three steps of reactions, i.e., acylation, coupling and deprotection. According to the surfactant, D-xylose obtained from crop leftovers can be thoroughly converted, the production cost is low, the preparation method is simple, and the product is environmentally friendly. The glycoside is improved in water solubility, relatively high in surface activity and optional and controllable in foamability and emulsifying property and has good market prospect and economic value as a surfactant.
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Paragraph 0039; 0040
(2017/07/19)
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- Efficient and selective N-, S- and O-acetylation in TEAA ionic liquid as green solvent. Applications in synthetic carbohydrate chemistry
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Background: The ionic liquid triethylammonium acetate (TEAA) was found to be an efficient solvent in the acetylation of alcohols, amines, oximes and thiols to their corresponding acetyl compounds using only a 10% excess of acetic anhydride under mild conditions. Moreover TEAA is not only an inexpensive and recyclable solvent but also an anomeric selective catalyst in the per-O-acetylation of sugar moieties. Methods: Simple and effective organic synthesis protocols were provided for the selective acetylation of several substrates. The products were fully characterized by 1H and 13C NMR spectroscopy and the anomeric ratios were obtained from the 1H spectra. Results: Structurally diverse alcohols, phenols, thiols, amines, carbohydrates and oximes underwent acylation under mild conditions by this procedure to provide the corresponding acetates in excellent yields. TEAA ionic liquid is unique in its capability to act as both, solvent and high selective catalyst. As expected, the reaction proceeds with high b anomeric selectivity for sugars derivatives. Moreover, the ionic liquid was regenerated, recycled and reused for three times without apparent loss of reactivity and selectivity in all cases. Conclusions: The present procedure provides a powerful and versatile acylation method for alcohols, phenols, thiols, amines, oximes and carbohydrates. This protocol is endowed with several unique merits: selectivity, cost-efficiency, atom-economy and mild reaction conditions tolerable to acid sensitive functionalities. With these features, this method may be considered as a better alternative for the acetylation of a wide range of substrates.
- Lafuente, Leticia,Díaz, Gisela,Bravo, Rodolfo,Ponzinibbio, Agustín
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p. 195 - 200
(2016/02/26)
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- Synthesis and Biological Evaluation of Novel Carbohydrate-Derived Derivatives of Erlotinib
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(Table presented.). A series of novel carbohydrate-derived Erlotinib derivatives were prepared by the copper-catalyzed cycloaddition reaction of erlotinib with various azido-sugars. The structures of the newly synthesized compounds were characterized and their cytostatic effects evaluated in vitro on human cancer cell lines MDA-MB-231, HEPG-2, A549, and MCF-7 using an MTS assay. The novel erlotinib derivatives had the expected inhibitory effects on MDA-MB-231 and HEPG-2 cell llines. Among the compounds evaluated the carbohydrate-derived compounds 5b, 5d, 6a, and 6c had more potent activities against MDA-MB-231 or HEPG-2 than Erlotinib. Drug Dev Res, 2016.
- Yu, Wenbo,Jiang, Luxia,Shen, Chao,Zhang, Pengfei
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p. 319 - 325
(2016/10/12)
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- Synthesis of Functionalized 2-(4-Hydroxyphenyl)-3-methylbenzofuran Allosteric Modulators of Hsp90 Activity
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Hsp90 is a molecular chaperone that plays a pivotal role in the cell life cycle. ATP-regulated internal dynamics are critical to Hsp90 function and we recently demonstrated that these dynamics can be modulated in an allosteric fashion; the protein C-terminal domain (CTD) can be effectively targeted with a family of 2-phenyl-benzofuran derivatives. Here we describe the expansion of the initial library, reporting 28 new derivatives that explore the chemical space at opposite ends of the benzofuran scaffold. Interactions of the compounds with a full-length protein homolog were explored by Saturation Transfer Difference (STD) NMR spectroscopy. In this context we also report the interaction epitope of Novobiocin, a known CTD inhibitor.
- Sattin, Sara,Panza, Matteo,Vasile, Francesca,Berni, Francesca,Goti, Giulio,Tao, Jiahui,Moroni, Elisabetta,Agard, David,Colombo, Giorgio,Bernardi, Anna
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p. 3349 - 3364
(2016/07/26)
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- Organoboron-Promoted Regioselective Glycosylations in the Synthesis of a Saponin-Derived Pentasaccharide from Spergularia ramosa
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Organoboron-mediated regioselective glycosylations were employed as key steps in the total synthesis of a branched pentasaccharide from a saponin natural product. The ability to use organoboron activation to differentiate OH groups in an unprotected glycosyl acceptor, followed by substrate-controlled reactions of the obtained disaccharide, enabled a streamlining of the synthesis relative to a protective group-based approach. This study revealed a matching/mismatching effect of the relative configuration of donor and acceptor on the efficiency of a regioselective glycosylation reaction, a problem that was solved through the development of a novel boronic acid-amine copromoter system for glycosyl acceptor activation.
- Mancini, Ross S.,McClary, Corey A.,Anthonipillai, Stefi,Taylor, Mark S.
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p. 8501 - 8510
(2015/09/15)
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- ARYLNAPHTHALENE LACTONE DERIVATIVES AND METHODS OF MAKING AND USING THEREOF
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A series of natural products including phyllanthusum, an arylnaphthalene lignan derivative, with anticancer and antitumor and immurtostimulating activity are disclosed. The invention further encompasses methods of adding water solubilizing groups to the arylrings that include phosphonyl groups.
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- Cu(ClO4)2·6H2O catalyzed solvent free per-O-acetylation and sequential one-pot conversions of sugars to thioglycosides
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The solvent free per-O-acetylation of various reducing and non-reducing sugars has been carried out using stoichiometric amounts of acetic anhydride and copper(ii) perchlorate hexahydrate as the catalyst. The reactions with various reducing monosaccharides have also been followed by a one-pot sequential conversion to the corresponding thioglycosides in high yields. This journal is
- Chatterjee, Debnath,Paul, Abhijit,Rajkamal,Yadav, Somnath
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p. 29669 - 29674
(2015/05/20)
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- I2/ionic liquid as a highly efficient catalyst for per-O-acetylation of sugar under microwave irradiation
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A practical and highly efficient approach was developed to synthesize peracetylated sugar derivatives using a recyclable iodine/PEG400-based ionic liquid catalyst (I2/IL). The peracetylated sugars were readily obtained in a few minutes in excellent yields (90%-99%, 13 examples) on a multi-gram scale (50.0 mmol) by the reaction of sugar and acetic anhydride under microwave irradiation in the absence of a volatile organic solvent. The desired product was easily obtained by simple extraction with toluene from the reaction mixture, and I2/ILs can be readily recovered and reused at least six times without obvious loss in the yield. When the scale of the per-O-acetylation reaction was increased to 50.0 mmol, the desired product was still obtained in 90% yield after five recycles.
- Xiong, Xingquan,Yi, Chao,Han, Qian,Shi, Lin,Li, Sizhong
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p. 237 - 243
(2015/09/28)
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- Atom-Economical Dimerization Strategy by the Rhodium-Catalyzed Addition of Carboxylic Acids to Allenes: Protecting-Group-Free Synthesis of Clavosolide A and Late-Stage Modification
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Natural products of polyketide origin with a high level of symmetry, in particular C2-symmetric diolides as a special macrolactone-based product class, often possess a broad spectrum of biological activity. An efficient route to this important
- Haydl, Alexander M.,Breit, Bernhard
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supporting information
p. 15530 - 15534
(2016/01/26)
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- Exploration of the active site of β4GalT7: Modifications of the aglycon of aromatic xylosides
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Proteoglycans (PGs) are macromolecules that consist of long linear polysaccharides, glycosaminoglycan (GAG) chains, covalently attached to a core protein by the carbohydrate xylose. The biosynthesis of GAG chains is initiated by xylosylation of the core protein followed by galactosylation by the galactosyltransferase β4GalT7. Some β-d-xylosides, such as 2-naphthyl β-d-xylopyranoside, can induce GAG synthesis by serving as acceptor substrates for β4GalT7 and by that also compete with the GAG synthesis on core proteins. Here we present structure-activity relationships for β4GalT7 and xylosides with modifications of the aromatic aglycon, using enzymatic assays, cell studies, and molecular docking simulations. The results show that the aglycons reside on the outside of the active site of the enzyme and that quite bulky aglycons are accepted. By separating the aromatic aglycon from the xylose moiety by linkers, a trend towards increased galactosylation with increased linker length is observed. The galactosylation is influenced by the identity and position of substituents in the aromatic framework, and generally, only xylosides with β-glycosidic linkages function as good substrates for β4GalT7. We also show that the galactosylation ability of a xyloside is increased by replacing the anomeric oxygen with sulfur, but decreased by replacing it with carbon. Finally, we propose that reaction kinetics of galactosylation by β4GalT7 is dependent on subtle differences in orientation of the xylose moiety. This journal is
- Siegbahn, Anna,Thorsheim, Karin,St?hle, Jonas,Manner, Sophie,Hamark, Christoffer,Persson, Andrea,Tykesson, Emil,Mani, Katrin,Westergren-Thorsson, Gunilla,Widmalm, G?ran,Ellervik, Ulf
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p. 3351 - 3362
(2015/03/18)
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- In(III) triflate-mediated solvent-free synthesis and activation of thioglycosides by ball milling and structural analysis of long chain alkyl thioglycosides by TEM and quantum chemical methods
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Conventional solution-phase synthesis of thioglycosides from glycosyl acetates and thiols in the presence of In(III) triflate as reported for benzyl thioglucoside failed when applied to the synthesis of phenolic and alkyl thioglycosides. But, it was achieved in high efficiency and diastereospecificity with ease by solvent-free grinding in a ball mill. The acetates in turn were also obtained by the homogenization of free sugars with stoichiometric amounts of acetic anhydride and catalytic In(OTf)3 in the mill as neat products. Per-O-benzylated thioglycosides on grinding with an acceptor sugar in the presence of In(OTf)3 yield the corresponding O-glycosides efficiently. The latter in the case of a difficult secondary alcohol was nearly exclusive (>98%) in 1,2-cis-selectivity. In contrast, the conventional methods for this purpose require use of a coreagent such as NIS along with the Lewis acid to help generate the electrophilic species that actually is responsible for the activation of the thioglycoside donor in situ. The distinctly different self-assembling features of the peracetylated octadecyl 1-thio-α- and β-d-galactopyranosides observed by TEM could be rationalized by molecular modeling.
- Kumar, Vajinder,Taxak, Nikhil,Jangir, Ramniwas,Bharatam, Prasad V.,Kartha, K. P. Ravindranathan
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p. 3427 - 3439
(2014/05/06)
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- Carbohydrate-derived iminium salt organocatalysts for the asymmetric epoxidation of alkenes
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A new family of carbohydrate-based dihydroisoquinolinium salts has been prepared and tested for potential as asymmetric catalysts for the epoxidation of unfunctionalized alkene substrates, providing up to 57% ee in the product epoxides.
- Bulman Page, Philip C.,Chan, Yohan,Liddle, John,Elsegood, Mark R.J.
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p. 7283 - 7305
(2017/09/13)
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- Sulfonic acid functionalized nano γ-Al2O3 catalyzed per-O-acetylated of carbohydrates
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A simple and clean synthesis of per-O-acetylation carbohydrate derivatives has been accomplished by treatment of sugars with a stoichiometric quantity of acetic anhydride under solvent-free conditions in the presence of sulfonic acid functionalized nano γ-Al2O3 as an efficient and environmentally benign catalyst.
- Wu, Liqiang,Yin, Zhikui
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- Glycosynthase with broad substrate specificity-an efficient biocatalyst for the construction of oligosaccharide library
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A versatile glycosynthase (TnG-E338A) with strikingly broad substrate scope has been developed from Thermus nonproteolyticus β-glycosidase (TnG) by using site-directed mutagenesis. The practical utility of this biocatalyst has been demonstrated by the facile generation of a small library containing various oligosaccharides and a steroidal glycoside (total 25 compounds) in up to 100 % isolated yield. Moreover, an array of eight gluco-oligosaccharides has been readily synthesized by the enzyme in a one-pot, parallel reaction, which highlights its potential in the combinatorial construction of a carbohydrate library that will assist glycomic and glycotherapeutic research. Significantly, the enzyme provides a means by which glycosynthase technology may be extended to combinatorial chemistry.
- Wei, Jinhua,Lv, Xun,Lue, Yang,Yang, Gangzhu,Fu, Lifeng,Yang, Liu,Wang, Jianjun,Gao, Jianhui,Cheng, Shuihong,Duan, Qian,Jin, Cheng,Li, Xuebing
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supporting information
p. 2414 - 2419
(2013/05/23)
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- Design, synthesis and biological evaluation of azithromycin glycosyl derivatives as potential antibacterial agents
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A series of 11,12-cyclic carbonate azithromycin-4″-O-carbamoyl glycosyl derivatives were designed, synthesized, and evaluated as antibacterial agents to search for target compounds with excellent activity. The results of preliminary antibacterial tests against eight strains in vitro revealed that all of the title compounds exhibited improved activities with broad spectrum compared with the parent compound. The glycosylated side chains may be the pharmacophores responsible for the improved activity.
- Zhang, Lei,Chai, Xiaoyun,Wang, Baogang,Yu, Shichong,Hu, Honggang,Zou, Yan,Zhao, Qingjie,Meng, Qingguo,Wu, Qiuye
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p. 5057 - 5060
(2013/09/12)
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- Cyclometalated gold(III) iminophosphoranes which incorporate carbohydrate groups
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Iminophosphoranes with organic groups derived from d-glucose, d-galactose and l-arabinose have been used to prepare gold(III) dichloride complexes via mercurated intermediates, since direct cyclometallation was unsuccessful. Structures and full spectroscopic data are reported. Replacement of one or more of the chloride ligands by PPh3, or by thiosalicylate gave new derivatives. Biological screening showed no enhanced activity relative to other alkyl or aryl analogues.
- Jarman, Bevan P.,Nicholson, Brian K.
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scheme or table
p. 1 - 9
(2012/03/12)
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- Biotransformation of spirolaxine by Absidia cuneospora and Trametes hirsuta: Formation of β-glycosyl and β-xylosyl derivatives
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Incubation of spirolaxine 1a with the fungus Absidia cuneospora afforded 5β-glucosyl-spirolaxine 2b; the structure of the biotransformed product was deduced on the basis of MS, NMR data and chemical semi-synthesis. When using Trametes hirsuta as a bioagent 1a afforded 5β-xylosyl-spirolaxine 3a; the identification of the sugar moiety came from acidic hydrolysis of the new metabolite.
- Bava, Adriana,Nasini, Gianluca,Fronza, Giovanni
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experimental part
p. 59 - 63
(2012/10/18)
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- Synthesis, thermal properties, and cytotoxicity evaluation of hydrocarbon and fluorocarbon alkyl β-d-xylopyranoside surfactants
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Alkyl β-d-xylopyranosides are highly surface active, biodegradable surfactants that can be prepared from hemicelluloses and are of interest for use as pharmaceuticals, detergents, agrochemicals, and personal care products. To gain further insights into th
- Xu, Wenjin,Osei-Prempeh, Gifty,Lema, Carolina,Davis Oldham,Aguilera, Renato J.,Parkin, Sean,Rankin, Stephen E.,Knutson, Barbara L.,Lehmler, Hans-Joachim
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scheme or table
p. 12 - 23
(2012/03/11)
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