- Highly enantioselective hydrophosphonylation of aldehydes catalyzed by tridentate Schiff base aluminum(III) complexes
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(Chemical Equation Presented) Active in dimeric form: A tridentate Schiff base aluminum(III) complex has been applied in the asymmetric hydrophosphonylation of various aldehydes, giving the corresponding products in good yields with good to excellent ee v
- Zhou, Xin,Liu, Xiaohua,Yang, Xu,Shang, Deju,Xin, Junguo,Feng, Xiaoming
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- Design, synthesis and evaluation of carbamate-linked uridyl-based inhibitors of human ST6Gal I
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Sialic acid at the terminus of cell surface glycoconjugates is a critical element in cell-cell recognition, receptor binding and immune responses. Sialyltransferases (ST), the enzymes responsible for the biosynthesis of sialylated glycans are highly upregulated in cancer and the resulting hypersialylation of the tumour cell surface correlates strongly with tumour growth, metastasis and drug resistance. Inhibitors of human STs, in particular human ST6Gal I, are thus expected to be valuable chemical tools for the discovery of novel anticancer drugs. Herein, we report on the computationally-guided design and development of uridine-based inhibitors that replace the charged phosphodiester linker of known ST inhibitors with a neutral carbamate to improve pharmacokinetic properties and synthetic accessibility. A series of 24 carbamate-linked uridyl-based compounds were synthesised by coupling aryl and hetaryl α-hydroxyphosphonates with a 5′-amino-5′-deoxyuridine fragment. The inhibitory activities of the newly synthesised compounds against recombinant human ST6Gal I were determined using a luminescent microplate assay, and five promising inhibitors with Ki’s ranging from 1 to 20 μM were identified. These results show that carbamate-linked uridyl-based compounds are a potential new class of readily accessible, non-cytotoxic ST inhibitors to be further explored.
- Dobie, Christopher,Hallam, Laura,Montgomery, Andrew P.,Ranson, Marie,Skropeta, Danielle,Szabo, Rémi,Yu, Haibo
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- Synthesis and anticancer cytotoxicity with structural context of an α-hydroxyphosphonate based compound library derived from substituted benzaldehydes
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We synthesized substituted benzaldehyde derived α-hydroxyphosphonates (αOHP), α-hydroxyphosphonic acids (αOHPA) and α-phosphinoyloxyphosphonates (αOPP) and characterized their cytotoxicity against a panel of cancer cell lines. A library containing 56 analogues was screened against Mes-Sa parental and Mes-Sa/Dx5 multidrug resistant uterine sarcoma cell lines, using a fluorescence-based cytotoxicity assay. The cytotoxicity screening revealed that dibenzyl-αOHPs and dimethyl-α-diphenyl-OPPs were the most active clusters, which encouraged us to synthesize further dibenzyl-α-diphenyl-OPP derivatives that elicited pronounced cell killing. Further structure-activity relationships showed the relevance of hydrophobicity and the position of substituents on the main benzene ring as determinants of toxicity. The most active analogs proved to be equally, or even more toxic to the multidrug resistant (MDR) cell line Mes-Sa/Dx5, suggesting these compounds may overcome P-glycoprotein mediated multidrug resistance by evading the drug transporter.
- Rádai, Zita,Windt, Tímea,Nagy, Veronika,Füredi, András,Kiss, Nóra Zsuzsa,Ranelovi?, Ivan,Tóvári, József,Keglevich, Gy?rgy,Szakács, Gergely,Tóth, Szilárd
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supporting information
p. 14028 - 14035
(2019/09/18)
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- Rational synthesis of α-hydroxyphosphonic derivatives including dronic acids
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New, green methods have been elaborated for the syntheses of α-hydroxyphosphonates and α-hydroxymethylenebisphosphonic derivatives (HMBPs, dronates). α-Hydroxyphosphonates were prepared via the Pudovik reaction, while the synthesis of HMBPs has been performed in the three-component reaction of carboxylic acids, phosphorus trichloride and phosphorus acid.
- Grün, Alajos,Rádai, Zita,S?regi-Nagy, Dávid Illés,Greiner, István,Keglevich, Gy?rgy
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p. 386 - 387
(2019/01/18)
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- Green synthesis and cytotoxic activity of dibenzyl α-hydroxyphosphonates and α-hydroxyphosphonic acids
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A series of dibenzyl α-hydroxyphosphonates and the corresponding α-hydroxyphosphonic acids, mostly new compounds, have been synthesized. The dibenzyl α-hydroxyphosphonates have been obtained in the Pudovik reaction of substituted benzaldehydes and dibenzyl phosphite in the presence of triethylamine as the catalyst. The amount of the solvent was minimized during the reaction, and the workup involved crystallization from the reaction mixture. A new protocol was developed to transform the dibenzyl 1-hydroxyphosphonates to the corresponding phosphonic acids by catalytic hydrogenation. The derivatives prepared were screened as potential cytotoxic agents against Mes-Sa human uterine sarcoma cell line.
- Rádai, Zita,Szeles, Petra,Kiss, Nóra Zsuzsa,Heged?s, László,Windt, Tímea,Nagy, Veronika,Keglevich, Gy?rgy
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- Manganese-proline derived new catalyst system for the enantioselective synthesis of α-hydroxyphosphonates and α-aminophosphonates
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A novel manganese/proline-derived catalyst system is reported for the stereoselective synthesis of α-hydroxyphosphonates and α-aminophosphonates. The reaction proceeded smoothly under mild reaction conditions with efficient reaction times. The resulting p
- Lim, Hyun,Datilus, Vicklyn,Teriak, Rania,Chohan, Prianka,Kaur, Parminder
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supporting information
p. 1480 - 1483
(2017/03/23)
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- Nafion-supported oxovanadium-catalyzed hydrophosphonylation of aldehydes under solventless conditions
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A Nafion resin-supported oxovanadium(IV) catalyst was readily prepared via ion-exchange method. This solid vanadyl perfluorinated sulfonate catalyst was used as an efficient and recoverable catalyst for the hydrophosphonylation of various aldehydes under solventless conditions at room temperature. The catalyst could be recovered by simple filtration and reused without a significant loss of activity.
- Weng, Shiue-Shien,Lin, Guan-Ying,Li, Hsin-Chun,Yang, Kuo-Chen,Yang, Teng-Mao,Liu, Hui-Chi,Sie, Syuan-Hua
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p. 455 - 460
(2012/10/29)
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- Kinetic resolution of (±)-diethyl- and dibenzyl hydroxy(phenyl) methanephosphonates and their acyl derivatives with lipases
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A wide variety of commercially available lipases and microbial whole cells were tested for biotransformations of (±)-diethyl and dibenzyl hydroxyl(phenyl)methanephosphonates. Biocatalytic hydrolysis of acylated hydroxyphosphonates by whole cells of Bacillus subtilis gave optically active compounds with 95%eeS. Enantioselectivities obtained when using commercially available enzymatic preparations were less satisfactory, leading to both compounds with an enantiomeric excess in the range 15-35%. Screening lipases for their ability to acylate these phosphonates or to hydrolyze their acylated derivatives enabled selection of enzymes and organisms suitable for use in both processes.
- Malinowska, Barbara,Majewska, Paulina,Szatkowski, Pawel,Kafarski, Pawel,Lejczak, Barbara
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p. 271 - 277
(2012/03/27)
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- A Simple, Efficient Synthesis of Dibenzyl and Di-p-nitrobenzyl 1-Hydroxyalkanephosphonates
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Dibenzyl and di-p-nitrobenzyl 1-hydroxyalkanephosphonates 3a-i are prepared by alkylation of 1-hydroxyalkanephosphonic acids 1 with O-benzyl and O-(p-nitrobenzyl)-N,N'-dicyclohexylisoureas 2.
- Hoffmann, Maria
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