64363-77-5Relevant articles and documents
Chemical synthesis of linear ADP-ribose oligomers up to pentamer and their binding to the oncogenic helicase ALC1
Filippov, Dmitri V.,Knobloch, Gunnar,Ladurner, Andreas G.,Liu, Qiang,Meeuwenoord, Nico J.,Overkleeft, Herman S.,Voorneveld, Jim,van der Marel, Gijsbert A.
, p. 12468 - 12475 (2021)
ADP-ribosylation is a pivotal post-translational modification that mediates various important cellular processes producing negatively charged biopolymer, poly (ADP-ribose), the functions of which need further elucidation. Toward this end, the availability
Synthesis of remdesivir key intermediate 2, 3, 5-tribenzyloxy-D-ribotide-1, 4-lactone
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Paragraph 0018; 0022-0024, (2020/07/21)
The invention relates to synthesis of a remdesivir key intermediate 2, 3, 5-tribenzyloxy-D-ribotide-1, 4-lactone. The invention discloses a synthesis method of 2, 3, 5-tribenzyloxy-D-ribotide-1, 4-lactone, and belongs to the field of organic synthesis. The method includes: taking D-ribose as an initial raw material, in methanol, using concentrated sulfuric acid as a catalyst, synthesizing a methoxy compound 2, then fully stirring the substances in a saturated sodium hydroxide solution, adding tetrahydrofuran and n-butylammonium hydrogen sulfate, and then adding benzyl bromide to synthesize a compound 3, dissolving the compound 3 in tetrahydrofuran and then performing catalysis with concentrated sulfuric acid, and performing reflux stirring overnight treatment to obtain a compound 4, dissolving the compound 4 into dichloromethane and water, adding sodium bicarbonate and TEMPO, slowly adding sodium hypochlorite at 0DEG C, raising the temperature to room temperature, and conducting stirring overnight treatment to obtain a compound 5. The method has the characteristics of easily available raw materials and low production cost, each process step is simple and easy to treat, the yield ofthe whole route reaches 43% or above, industrial production is easy to realize, and a basis is provided for industrialization of remdesivir and subsequent derivatives thereof.
Computer Modelling and Synthesis of Deoxy and Monohydroxy Analogues of a Ribitylaminouracil Bacterial Metabolite that Potently Activates Human T Cells
Ler, Geraldine J. M.,Xu, Weijun,Mak, Jeffrey Y. W.,Liu, Ligong,Bernhardt, Paul V.,Fairlie, David P.
, p. 15594 - 15608 (2019/11/16)
5-(2-Oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) is a natural product formed during bacterial synthesis of vitamin B2. It potently activates mucosal associated invariant T (MAIT) cells and has immunomodulatory, inflammatory, and anticancer properties. This highly polar and unstable compound forms a remarkably stable Schiff base with a lysine residue in major histocompatibility complex class I–related protein (MR1) expressed in antigen-presenting cells. Inspired by the importance of the ribityl moiety of 5-OP-RU for binding to both MR1 and the T cell receptor (TCR) on MAIT cells, each OH was removed in silico. DFT calculations and MD simulations revealed a very stable hydrogen bond between the C3′?OH and uracil N1H, which profoundly restricts flexibility and positioning of each ribityl-OH, potentially impacting their interactions with MR1 and TCR. By using deoxygenation strategies and kinetically controlled imine formation, four monodeoxyribityl and four monohydroxyalkyl analogues of 5-OP-RU were synthesised as new tools for probing T cell activation mechanisms.