6979-97-1Relevant articles and documents
Synthesis and photophysical properties of 5-(3′′-alkyl/aryl-amino-1′′-azaindolizin-2′′-yl)-2′-deoxyuridines
Bali Mehta, Shilpika,Kumar, Banty,Kumar, Sandeep,Kumar, Sumit,Maity, Jyotirmoy,Prasad, Ashok K.
, p. 16635 - 16647 (2021/09/27)
The Groebke-Blackburn-Bienayame (GBB) reaction has been used for the efficient synthesis of novel fluorescent 5-azaindolizino-2′-deoxyuridines starting from commercially available thymidine following two strategies. Thus, thymidine was converted to diacetylthymidine, which on potassium persulphate oxidation afforded 3′,5′-di-O-acetyl-5-formyl-2′-deoxyuridine. In strategy A, diacetylated 5-formyldeoxyuridine was reacted with a variety of 2-aminopyridines and alkyl/aryl isocyanides under optimized GBB reaction conditions followed by deacetylation of the resulting GBB products to afford 5-azaindolizino-2′-deoxyuridines in 83 to 95% overall yields. In strategy B, diacetylated 5-formyldeoxyuridine was first deacetylated, which on GBB reaction under standardised conditions with 2-aminopyridines and alkyl/aryl isocyanides afforded the desired 5-azaindolizino-2′-deoxyuridines in 21 to 23% overall yields, which clearly indicates that strategy A is far more efficient than strategy B. The emission spectra of the synthesized 5-azaindolizino-2′-deoxyuridines exhibited a strong band around 360 nm (excitation at 239 nm) in fluorescence studies. Photophysical studies of these nucleosides showed a high level of fluorescence with Stokes shift in the range 59-126 nm, which indicated their potential for the study of the local structure and dynamics of nucleic acids involving them.
4 - Thiodeoxythymidine derivative and anti-hepatitis B virus pharmaceutical application thereof
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Paragraph 0043-0044, (2021/10/05)
4 - Thio-deoxythymidine derivatives and anti-hepatitis B virus pharmaceutical applications thereof are disclosed. The invention provides 4 - thiodeoxythymidine derivative or a pharmaceutically acceptable salt thereof, and the structure is shown in structural formula I or structural formula II. An in-vitro cytotoxicity test and an in-vitro anti HBV virus pharmacodynamic test proves 4 - thiodeoxythymidine derivative or a pharmaceutically acceptable salt thereof has anti HBV activity, has an anti-hepatitis B drug development prospect and provides a potential choice for treating viral hepatitis.
SYNTHESIS AND IMPROVEMENT OF A NUCLEOSIDE ANALOGUE AS AN ANTI-CANCER AND ANTI-VIRAL DRUG
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, (2021/05/29)
The invention is a drug for anticancer and antiviral therapy, comprising a nucleoside analogue (7) comprising a furan ring irreversibly bound to the RNA/DNA synthesis chain by phosphodiester bonds and having SP3 hybridization, and folic acid (A) bound to the nucleoside analogue (7) comprising furan ring. The synthesis method of the said nucleoside analogue is also contained within the scope of the invention. In this work, a nucleoside-analogue was transformed after converting the furan-ring hybridization from Sp2 to Sp3 to make it more selectivity with different enzymes and linking it via site 5 with the effective folic acid towards entering the substances inside the cells and to become the final compound possessing anti-cancer and anti- virus properties after controlling the replication and reproduction process in DNA.
A synergistic synthetic and computational insights towards anomerization of N-nitro pyrimidine nucleosides using fluorinating agents
Bayach, Imene,Khalil, Ahmed,Mathé, Christophe
, (2020/03/18)
DAST and Deoxofluor are usually used for nucleophilic fluorination of nucleosides via SN1 or SN2 mechanism. DAST and Deoxo-fluor could enhance anomerization of N-substituted thymidine and 2′-deoxyuridine in dichloromethane into the more stable and favored α-anomers due to in-situ liberation of HF. This is strongly supported by computational calculations based on the density functional theory, that were performed to rationalize energy stability and electronic properties of both anomers in order to provide further insights into the proposed mechanism.
Light-Induced Formation of Thymine-Containing Mercury(II)-Mediated Base Pairs
Naskar, Shuvankar,Müller, Jens
supporting information, p. 16214 - 16218 (2019/11/26)
By applying caged thymidine residues, DNA duplexes were created in which HgII-mediated base pair formation can be triggered by irradiation with light. When a bidentate ligand was used as the complementary nucleobase, an unprecedented stepwise formation of different metal-mediated base pairs was achieved.
Syntheses of C-6 Aryl- and Alkynyl-Substituted Thymidines from Thymidine trans-5,6-Bromohydrins
Wrigstedt, Pauli,Iashin, Vladimir,Lagerblom, Kalle,Keskiv?li, Juha,Chernichenko, Konstantin,Repo, Timo
, p. 880 - 891 (2017/02/15)
C-6-substituted thymidines are biochemically important compounds. The thymidine (6–4) photoproduct [i.e., 5-hydroxy-6-(thymidine-4-yl) dihydrothymidine], in particular, is a DNA lesion that is triggered by the UV irradiation of sunlight. Herein, we report a metal-free cis-diastereoselective ring opening of thymidine 5,6-epoxides by using mildly nucleophilic organofluoroborates in the presence of BF3·Et2O to provide facile access to (6–4) photoproduct analogues. A broad range of aryl and alkynylfluoroborates are compatible with the reaction conditions, which also tolerate various protecting groups. Furthermore, the epoxide addition products can undergo a thionyl chloride/pyridine promoted dehydration process to give the respective pharmaceutically attractive C-6-substituted thymidines in high yields, thus providing a new and straightforward method for their synthesis.
Biocatalytic Process Optimization for the Production of High-Added-Value 6-O-Hydroxy and 3-O-Hydroxy Glycosyl Building Blocks
Callaghan, Ciara,Redmond, Martin,Alnoch, Robson Carlos,Mateo, Cesar,Filice, Marco,Palomo, Jose M.
, p. 2536 - 2543 (2017/07/13)
A biocatalytic process to synthesize regioselective monohydroxy glycosyl building blocks has been optimized. Lipases immobilized on commercial supports were treated with water-soluble carbodiimide (EDC) at different concentrations. In the presence of cosolvents, the stability of lipases adsorbed on octyl-Sepharose improved after the EDC modification. The new Candida rugosa lipase (CRL) modified heterogeneous biocatalysts were tested in the production of 6-OH hydroxyl-tetraacetyl glucose by a regioselective mono-deacetylation in aqueous media. Improvements in activity and excellent regioselectivity were obtained for octyl-CRL-EDC10mM preparation, with 95 % isolated yield of product on a multimilligram scale. We also observed excellent recyclability. The C-6 alcohol was transformed to a C-3 alcohol by chemical migration, and both compounds were transformed successfully in the corresponding new trichloroacetimidyl glucoderivatives. Modified CRL biocatalysts were also tested in the selective deprotection of peracetylated thymidine, and octyl-CRL-EDC10mM showed excellent specificity and improved regioselectivity to produce 3-hydroxy-5-acetyl-thymidine, a precursor of azidethymidine (AZT), in 95 % yield. The new Rhizomucor miehei lipase (RML)-modified heterogeneous biocatalysts showed excellent regioselectivity and recyclability in the 3-OH mono-deprotection of peracetylated lactal.
Efficient and green approach for the complete deprotection of O-acetylated biomolecules
Dunne, Anthony,Palomo, Jose M.
, p. 88974 - 88978 (2016/10/03)
A simple, efficient and mild strategy for the complete O-deacetylation of different per-acetylated biomolecules in aqueous media has been described. Different lipases were tested but only the commercial Amano lipase A from Aspergillus Niger catalyzed the complete deprotection of peracetylated α-glucose to glucose in excellent yield. The experimental conditions were tested, in particular the pH effect. The reaction was performed at different pHs considering the only enzymatic process was evaluated at pH 5 and the combination of enzymatic and chemical migration process was evaluated at higher pHs. Finally pH 7 and 25 °C were selected as best conditions. Thus this lipase fully hydrolyzed different peracetylated α-glycopyranosides (glucose, mannose, glucal, galactal) with >99% yields, whereas very good deprotecting yields (75-80%) were achieved for different acetylated β-glycopyranosides (galactose, ribofuranose) under these mild conditions. This strategy was successfully extended to the fully O-selective deprotection of acetylated nucleosides where >99% yield was rapidly obtained. No selectivity was observed for the N-deacetylation in amino acids and peptides.
Synthesis of novel caged antisense oligonucleotides with fluorescence property
Hikage, Shin,Sasaki, Yasuo,Hisai, Terunobu,Tanimoto, Hiroki,Morimoto, Tsumoru,Nishiyama, Yasuhiro,Kakiuchi, Kiyomi
, p. 175 - 183 (2016/11/16)
In this study, novel caged antisense oligonucleotides with thiochromone S,S-dioxide as the photolabile protecting group were synthesized, and their photodeprotection was investigated. In vitro experiment, the original target molecule was successfully reco
In search of Flavivirus inhibitors part 2: Tritylated, diphenylmethylated and other alkylated nucleoside analogues
Saudi, Milind,Zmurko, Joanna,Kaptein, Suzanne,Rozenski, Jef,Neyts, Johan,Van Aerschot, Arthur
, p. 98 - 109 (2014/03/21)
Several flaviviruses, such as the yellow fever virus and the dengue virus cause severe and potentially lethal infection in man. Following up on our initial hit 3′,5′-bistritylated uridine 1, a series of alkylated nucleoside analogues were synthesized and evaluated for their in vitro antiviral activities against dengue fever virus and yellow fever virus. Hereto, alkyl and aryl groups were attached at various positions of the sugar ring combined with subtle variation of the heterocyclic base. Among the new series of derivatives, 3′,5′-di-O-trityl-5-fluoro-2′-deoxyuridine (39) was the most efficient in this series and inhibited both yellow fever virus and dengue virus replication with a 50% effective concentration (EC50) of ～1 μg/mL without considerable cytotoxicity. The other fluorinated derivatives proved more toxic. Almost all diphenylmethylated pyrimidine nucleosides with 3′,5′-di-O-benzhydryl-2′-deoxyuridine (50) as the example were endowed with strong cytotoxic effects down to 1 μg/mL.
