3736-77-4Relevant articles and documents
The 2′-caged-tethered-siRNA shows light-dependent temporal controlled RNAi activity for GFP gene into HEK293T cells
Bollu, Amarnath,Hassan, Md. Khurshidul,Dixit, Manjusha,Sharma, Nagendra K.
, (2021)
Small interfering RNA (siRNA) exhibits gene-specific RNAi activity by the formation of RISC complex with mRNA of gene. The structural modification of siRNA at appropriate positions affects the structure of RISC complex and then RNAi activity. The modified siRNA are mostly prepared from the incorporation of sugar ring modified, and nucleobase modified RNA nucleotides. It is learned that the introduction of the sterically hindered nucleoside at the specific position of siRNA, severely affects siRNA-RISC complex formation. This report describes the syntheses of bulkier siRNA from 2′-caged-tethered-siRNAs, containing bulkier photolabile protecting group (o-nitrobenzyl) at 2′-position of ribose nucleoside. Importantly, these 2′-caged-siRNAs exhibit the light-dependent RNA interference (RNAi) activity into HEK293T cells for the GFP gene expression. The 2′-caged-siRNAs are synthesized by caging the sense and antisense strand of siRNA. The biochemical evaluations of these caged-siRNAs show that antisense-strand caged-siRNAs decrease RNAi activity temporarily in dark while enhancing RNAi activity, almost like control, after exposure withUV- light. However, 2′-caged sense strand siRNA increase RNAi activity temporarily while decreasing RNAi activity after exposure with light. These caged-siRNAs are also stable in the serum (fetal bovine serum) as like native siRNA. Hence these results strongly support that 2′-caged-tethered-siRNAs are promising analogues to control RNAi activity by UV-light.
Simple and High radiochemical yield synthesis of 2'-Deoxy-2'-[18F]fluorouridine via a new nosylate precursor
Kang, Se Han,Oh, Seung Jun,Yoon, Mi Kyung,Ryu, Jin Sook,Lee, Won Koo,Choi, Sun Joo,Park, Kyung Pae,Moon, Dae Hyuk
, p. 1237 - 1246 (2006)
We synthesized 2'-deoxy-2'-[18F]fluorouridine (7) as a radiotracer for positron emission tomography from a new nosylate precursor (6). This new precursor was synthesized from uridine in four steps. The overall synthetic yield was 9.4 percent and we have high stability of >98 percent purity up to 6 months at 4 deg C. The optimal manual [18F]fluorination conditions were 30 mg of the precursor 6 in 500 μl of acetonitrile at 145 deg C for 15 min with 370 MBq of [18F]fluoride. The [18F]fluorination yield was 76.5 +/- 2.7 percent (n = 3). After hydrolysis of protecting groups with 1N HCl and purification by HPLC, the overall radiochemical yield and purity were 26.5 +/- 1.4 percent and 98.2 +/- 2.5 percent, respectively. The preparation time was 70.0 +/- 10.5 min (n = 3 for each result). We also developed an automated method with a radiochemical yield and purity of 24.0 +/- 2.8 and 98.0 +/- 1.5 percent (n = 10) using a GE TracerLab MX chemistry module. This new nosylate precursor for 2'-deoxy-2'-[18F]fluorouridine synthesis showed higher radiochemical yields and reproducibility than previous methods.
2′,3′-Anhydrouridine
Miah, Anwar,Reese, Colin B.,Song, Quanlai
, p. 407 - 408 (1997)
The previously unreported title compound 4 is readily obtained by treating 2,2′-anhydro-1-β-D-arabinofuranosyluracil 1 with sodium hydride in dry dimethyl sulfoxide at room temperature.
METHODS AND REAGENTS FOR SYNTHESIZING NUCLEOSIDES AND ANALOGUES THEREOF
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Paragraph 0066; 00288-00290, (2021/10/02)
The present invention relates to methods and intermediates for the synthesis of nucleosides and nucleoside analogues (NAs). More specifically, the present invention relates to methods of synthesizing nucleosides and NAs, using simple achiral materials by a 'one-pot' proline-catalyzed halogenation of a heteroaryl-substituted acetaldehyde together with a tandem enantioselective aldol reaction followed by a reduction or organometallic addition and cyclization (annulation) reaction involving halide displacement.
Site of azido substitution in the sugar moiety of azidopyrimidine nucleosides influences the reactivity of aminyl radicals formed by dissociative electron attachment
Mudgal, Mukesh,Dang, Thao P.,Sobczak, Adam J.,Lumpuy, Daniel A.,Dutta, Priya,Ward, Samuel,Ward, Katherine,Alahmadi, Moaadh,Kumar, Anil,Sevilla, Michael D.,Wnuk, Stanislaw F.,Adhikary, Amitava
, p. 11357 - 11370 (2020/12/23)
In this work, electron-induced site-specific formation of neutral π-type aminyl radicals (RNH·) and their reactions with pyrimidine nucleoside analogs azidolabeled at various positions in the sugar moiety, e.g., at 2′-, 3′-, 4′-, and 5′- sites along with a model compound 3-azido-1-propanol (3AZPrOH), were investigated. Electron paramagnetic resonance (EPR) studies confirmed the site and mechanism of RNH· formation via dissociative electron attachment-mediated loss of N2 and subsequent facile protonation from the solvent employing the 15N-labeled azido group, deuterations at specific sites in the sugar and base, and changing the solvent from H2O to D2O. Reactions of RNH· were investigated employing EPR by warming these samples from 77 K to ca. 170 K. RNH· at a primary carbon site (5′-azido-2′,5′-dideoxyuridine, 3AZPrOH) facilely converted to a σ-type iminyl radical (R=N·) via a bimolecular H-atom abstraction forming an α-azidoalkyl radical. RNH· when at a secondary carbon site (e.g., 2′-azido-2′-deoxyuridine) underwent bimolecular electrophilic addition to the C5=C6 double bond of a proximate pyrimidine base. Finally, RNH· at tertiary alkyl carbon (4′-azidocytidine) underwent little reaction. These results show the influence of the stereochemical and electronic environment on RNH· reactivity and allow the selection of those azidonucleosides that would be most effective in augmenting cellular radiation damage.
Synthesis of 2′-aminouridine derivatives as an organocatalyst for Diels-Alder reaction?
Wakamatsu, Hideaki,Itoh, Moeko,Natori, Yoshihiro,Yoshimura, Yuichi
, p. 365 - 383 (2019/08/12)
To develop a novel asymmetric organocatalyst based on a ribonucleoside skeleton, we designed and synthesized 2′-aminouridine derivatives. The synthesized 2′-aminouridines having bulky substituents at both base and sugar moieties could catalyze the Diels-Alder reaction between cinnamaldehyde and cyclopentadiene. However, the optical purities of the resulting products were unexpectedly low.
RELEASABLE CONJUGATES
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, (2018/09/28)
The present application provides compounds of Formula (B), or pharmaceutically acceptable salts thereof, wherein D is a residue of a biologically active drug, which underdo hydrolysis under physiological conditions to release the biologically active drug and which are useful in the treatment of disorders that could be beneficially treated with the drug.
A (2 'R) -2' - deoxy -2 '- fluoro -2' - methyl urea glucoside preparation method (by machine translation)
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Paragraph 0018, (2017/02/28)
The invention discloses a (2 'R) -2' - deoxy -2 '- fluoro -2' - methyl urea glucoside (type I) synthetic method. Cheap and easily available starting material, through the hydroxyl protection, cyclization, the links such as fluoride, obtains the type I compound. (by machine translation)
3-methyl uridine and 4-methyl cytidine nucleoside compound, synthetic method and its pharmaceutical use
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Paragraph 0021; 0034, (2016/10/08)
The invention discloses a 3-methyluridine and 4-methylcytidine nucleosides compound and a synthesis method and pharmaceutical application thereof, belonging to the field of medicinal chemistry. The compound has a structural formula as shown in the specification. The compound has the effects of simultaneously modifying sugar rings and basic groups, increasing the activity of the compound and reducing the toxicity, provides a good application prospect for development of like medicines and can be applied to preparation of anti-HBV (Hepatitis B virus) medicines. The synthesis method is simple and feasible and provides conditions for mass synthesis of the compound.
Versatile synthesis of 2′-amino-2′-deoxyuridine derivatives with a 2′-amino group carrying linkers possessing a reactive terminal functionality
Gondela, Andrzej,Tomczyk, Mateusz D.,Przypis, ?ukasz,Walczak, Krzysztof Z.
, p. 5626 - 5632 (2016/08/17)
2,2′-Anhydrouridine has been successfully converted into the appropriate 2′-amino-2′-deoxyuridine derivatives in a reaction with isothiocyanates obtained from amino acids or α,ω-diaminoalkanes. The initially formed oxazolidine-2-thione ring is cleaved under basic conditions into the corresponding 2′-amino(substituted)-2′-deoxyuridine derivatives. The implemented additional terminal functionality in the substituent attached to the 2′-amino group allows further modifications with e.g., fluorophore moiety.
