37085-43-1

Upstream product

• 2073-43-0 2',3'-O,O-isopropylidene-5-methyluridine 
• 98-59-9 p-toluenesulfonyl chloride 
• 1463-10-1 5-Methyluridine 
• 3816-77-1 2',3'-O-isopropylidene-5-hydroxymethyl-uridine 
• 161986-79-4 1-((3aR,4R,6R,6aR)-6-Hydroxymethyl-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl)-5-(2H-quinolin-1-ylmethyl)-1H-pyrimidine-2,4-dione 
• 149204-06-8 1,2,3,4-tetrahydro-1-(2',3'-O-isopropylidenethymidyl)-quinoline 
• 60170-16-3 2,3-O-isopropylidene-5-ethoxycarbonylpropylaminomethyluridine 

Relevant academic research and scientific papers

Tightly linked morpholino-nucleoside chimeras: new, compact cationic oligonucleotide analogues

The polyanionic phosphodiester backbone of nucleic acids contributes to high nuclease sensitivity and low cellular uptake and is therefore a major obstacle to the biological application of native oligonucleotides. Backbone modifications, particularly charge alterations is a proven strategy to provide artificial oligonucleotides with improved properties. Here, we describe the synthesis of a new type of oligonucleotide analogues consisting of a morpholino and a ribo- or deoxyribonucleoside in which the 5′-amino group of the nucleoside unit provides the nitrogen of the morpholine ring. The synthetic protocol is compatible with trityl and dimethoxytrityl protecting groups and azido functionality, and was extended to the synthesis of higher oligomers. The chimeras are positively charged in aqueous medium, due to theN-alkylated tertiary amine structure of the morpholino unit.

A low-temperature, photoinduced thiol-ene click reaction: A mild and efficient method for the synthesis of sugar-modified nucleosides

Sugar-modified nucleosides are prime synthetic targets in anticancer and antiviral drug development. Radical mediated thiol-ene coupling was applied for the first time on nucleoside enofuranoside derivatives to produce a broad range of thio-substituted d-ribo, -arabino, -xylo and l-lyxo configured pyrimidine nucleosides. In contrast to the analogous reactions of simple sugar exomethylenes, surprisingly, hydrothiolation of nucleoside alkenes under the standard conditions of various initiation methods showed low to moderate yields and very low stereoselectivity. Optimizing the reaction conditions, we have found that cooling the reaction mixture has a significant beneficial effect on both the conversion and the stereoselectivity, and UV-light initiated hydrothiolation of C2′-, C3′- and C4′-exomethylene derivatives of nucleosides at -80 °C proceeded in good to high yields, and, in most cases, in excellent diastereoselectivity. Beyond the temperature, the solvent, the protecting groups on nucleosides and, in some cases, the configuration of the thiols also affected the stereochemical outcome of the additions. The anomalous l-lyxo diastereoselectivity observed upon the addition of 1-thio-β-d-gluco- and galactopyranose derivatives onto C4′,5′-unsaturated uridines is attributed to steric mismatch between the d-ribo C4′-radical intermediates and the β-configured 1-thiosugars.

Synthesis and structure-activity relationship of uracil nucleotide derivatives towards the identification of human P2Y6 receptor antagonists

P2Y6 receptor (P2Y6-R) is involved in various physiological and pathophysiological events. With a view to set rules for the design of UDP-based reversible P2Y6-R antagonists as potential drugs, we established structure-activity relationship of UDP analogues, bearing modifications at the uracil ring, ribose moiety, and the phosphate chain. For instance, C5-phenyl- or 3-NMe-uridine-5′-α,β-methylene-diphosphonate, 16 and 23, or lack of 2′-OH, in 12-15, resulted in loss of both agonist and antagonist activity toward hP2Y6-R. However, uridylyl phosphosulfate, 19, selectively inhibited hP2Y6-R (IC50 112 μM) versus P2Y2/4-Rs. In summary, we have established a comprehensive SAR for hP2Y6-R ligands towards the development of hP2Y6-R antagonists.

Synthesis and biological activities of novel s-triazine bridged dinucleoside analogs

A series of novel dinucleosides linked by s-triazine were synthesized via the nucleophilic substitution reaction of amino nucleoside and cyanuric chloride in THF/H2O. The biological activities of these novel dinucleoside analogs against HIV-RT, HeLa and A-549 cell lines in vitro were evaluated. Copyright

Insight into the chemical mechanism of thymidylate synthase-catalyzed reaction through the evaluation of chemical models: The role of C6 sulfhydryl addition during the reductive elimination step of the reaction

Thymidylate synthase catalyzes the last step of the de novo synthesis of thymidine-5'-monophosphate (TMP), which has long been a target for the development of effective anticancer agents. Model compounds (15, 16, 17) were used to study the effect of C6 nucleophilic addition on the reductive elimination step of the TS-catalyzed reaction. Results suggest that C6 addition facilitates the reductive elimination of the H2folate moiety of the ternary intermediate (3). Therefore, the reaction pathway (pathway (b)) with the participation of C6 sulfhydryl addition during the reductive elimination process is the energetically favored process. Consequently, the elimination of the cysteine sulfhydryl group from the C6 position is the last step of the reaction before the dissociation of the products from the enzyme.