59989-18-3Relevant articles and documents
Studies on uracil derivatives and analogs. Syntheses of 5-(β-trimethylsilyl)ethynyluracil and 5-ethynyluracil
Kundu,Schmitz
, p. 463 - 464 (1982)
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Synthesis and biological evaluation of 5-(alkyn-1-yl)-1-(p-toluenesulfonyl) uracil derivatives
Janeba, Zlatko,Balzarini, Jan,Andrei, Graciela,Snoeck, Robert,De Clercq, Erik,Robins, Morris J.
, p. 580 - 586 (2006)
Sonogashira coupling of 5-iodouracil (2) and trimethylsilylacetylene gave 5-(trimethylsilylethynyl)uracil (3), which was deprotected to give 5-ethynyluracil (4). Copper(I)-catalyzed cyclization of 4 gave furo[2,3-d]pyrimidin-2(3H)-one (5). Tosylation of 2 and 4 gave the 1-(p-toluenesulfonyl) derivatives 6 and 7, respectively. The tosylated compound 6 and trimethylsilylacetylene did not undergo Sonogashira coupling, and copper(I)-catalyzed cyclization of 7 did not occur. Coupling of 2 with several terminal alkynes gave 5-(alkyn-1-yl)uracil derivatives (9), which underwent tosylation to produce the targeted 5-(alkyn-1-yl)-1-(p-toluenesulfonyl)uracil compounds (11). Copper(I)-catalyzed cyclization of 9 gave the respective furopyrimidines (10) in low yields. Again, cyclization did not occur with the tosyl derivatives (11). Activity against varicella-zoster virus (VZV) was observed with longer-chain analogues of 9 and 11, and compound 7 showed activity against human cytomegalovirus (HCMV) at near cytotoxic levels.
5-Triazolyluracils and their N1-sulfonyl derivatives: Intriguing reactivity differences in the sulfonation of triazole N1′-substituted and N1′-unsubstituted uracil molecules
Saftic, Dijana,Vianello, Robert,?inic, Biserka
, p. 7695 - 7704 (2015)
We describe the synthesis of novel C5-triazolyl derived N1-sulfonylpyrimidines through CuI-catalyzed alkyne-azide cycloaddition followed by sulfonylation of the formed C5-triazolyl derivatives with various sulfonyl chlorides under basic conditions. In the latter step, an intriguing difference in the reactivity of the pyrimidine N1 was observed that depended on the nature of the substituent at a distant triazole N1′ site. The N1′-unsubstituted compounds gave very small amounts of sulfonylation products, whereas N1′-substituted systems produced high yields of the respective N1-sulfonyl-5-(1,2,3-triazol-4-yl)uracils. Computational analysis revealed a close correlation between the strength of the employed base catalysts and their abilities to increase the nucleophilicity of the uracil N1 atom through subsequent deprotonation, leading to more products. Following this step, the phosphazene tBu-P4 superbase was applied in the sulfonylation, resulting in exclusive formation of the triazole N1′-unsubstituted N1-sulfonylpyrimidines. The synthesis of C5-triazolyl-substituted pyrimidines and C5-triazolyl derived N1-sulfonylpyrimidines is described. Computational studies of the sulfonation step shed light on the differences in reactivity and revealed a connection between the strength of the employed base and its tendency to increase the nucleophilicity of the reacting uracil N1 atom by deprotonation.
The Peculiar Case of the Hyper-thermostable Pyrimidine Nucleoside Phosphorylase from Thermus thermophilus**
Kaspar, Felix,Neubauer, Peter,Kurreck, Anke
, p. 1385 - 1390 (2021/01/29)
The poor solubility of many nucleosides and nucleobases in aqueous solution demands harsh reaction conditions (base, heat, cosolvent) in nucleoside phosphorylase-catalyzed processes to facilitate substrate loading beyond the low millimolar range. This, in turn, requires enzymes that can withstand these conditions. Herein, we report that the pyrimidine nucleoside phosphorylase from Thermus thermophilus is active over an exceptionally broad pH (4–10), temperature (up to 100 °C) and cosolvent space (up to 80 % (v/v) nonaqueous medium), and displays tremendous stability under harsh reaction conditions with predicted total turnover numbers of more than 106 for various pyrimidine nucleosides. However, its use as a biocatalyst for preparative applications is critically limited due to its inhibition by nucleobases at low concentrations, which is unprecedented among nonspecific pyrimidine nucleoside phosphorylases.
Design and synthesis of O-GlcNAcase inhibitors via 'click chemistry' and biological evaluations
Li, Tiehai,Guo, Lina,Zhang, Yan,Wang, Jiajia,Li, Zhonghua,Lin, Lin,Zhang, Zhenxing,Li, Lei,Lin, Jianping,Zhao, Wei,Li, Jing,Wang, Peng George
experimental part, p. 1083 - 1092 (2011/06/22)
Protein O-GlcNAcylation has been shown to play an important role in a number of biological processes, including regulation of the cell cycle, DNA transcription and translation, signal transduction, and protein degradation. O-GlcNAcase (OGA) is responsible for the removal of O-linked β-N-acetylglucosamine (O-GlcNAc) from serine or threonine residues, and thus plays a key role in O-GlcNAc metabolism. Potent OGA inhibitors are useful tools for studying the cellular processes of O-GlcNAc, and may be developed as drugs for the treatment neurodegenerative diseases. In this study, Cu(I)-catalyzed 'Click' cycloaddition reactions between glycosyl azides and alkynes were exploited to generate inhibitory candidates of OGA. Enzymatic kinetic screening revealed that compound 7 was a potent competitive inhibitor of human O-GlcNAcase (Ki = 185.6 μM). Molecular docking simulations of compound 7 into CpOGA (Clostridium perfringens OGA) suggested that strong π-π stacking interaction between the compound and W490 considerably contributed to improving the inhibitory activity. Crown Copyright
