Refernces
10.1016/j.tet.2008.01.133
The research focuses on the diastereoselective synthesis of D-xylo-isoxazolidinyl nucleosides, which are potentially active as antiviral and anticancer agents. The experiments involve the condensation of acetoxyisoxazolidines with silylated nucleobases such as uracil, thymine, cytosine, N-acetylcytosine, and guanine, using methods like the Vorbrüggen nucleosidation. The stereoselectivity of the addition depends on the structure of the substituent at C-3 from the starting chiral nitrone. The reactions were carried out under varying conditions, including different temperatures and solvents, to yield isoxazolidinyl b- and a-nucleosides with moderate to good stereoselectivity. The analyses used to determine the ratio of anomeric nucleosides, the stereochemistry, and the structure of the products included quantitative 13C NMR spectroscopy, NOE measurements, and mass spectrometry, with purification of the nucleosides achieved through flash column chromatography. The study also observed the formation of isoxazoline derivatives as side products under certain conditions and confirmed their structures using 2D NMR spectroscopy and chemical shift analysis.
10.1016/j.tet.2010.01.063
The research investigates the interactions between a series of novel bis-phenanthridinium–nucleobase conjugates and nucleotides. The study reveals that the adenine derivative of these conjugates exhibits high and selective affinity towards the complementary nucleotide UMP in an aqueous medium. This selective binding is attributed to specific changes in the UV–vis spectrum of phenanthridine subunits upon interaction with UMP, which differ significantly from changes caused by other nucleotides. Molecular modeling studies suggest that the stability and selectivity of the adenine-conjugate/UMP complex are correlated to the number of inter- and intramolecular aromatic stacking interactions between phenanthridinium subunits, covalently attached adenine, and added UMP. The selectivity is likely due to additional hydrogen bonding between UMP and adenine. Key chemicals involved in this research include bis-phenanthridinium–nucleobase conjugates, adenine, uracil, guanine, cytosine, and their respective nucleotides (AMP, UMP, GMP, CMP). The study also involves the use of various reagents such as tosyl chloride, pyridine, POCl3, NaOH, and DMF for the synthesis of the conjugates.
10.1021/jo902560f
The research focuses on the synthesis and biophysical evaluation of 20,40-constrained 20O-methoxyethyl (cMOE) and 20,40-constrained 20O-ethyl (cEt) nucleic acid analogues. The purpose of this study was to develop nucleoside modifications that combine the structural elements of 2O-methoxyethyl (MOE) and locked nucleic acid (LNA) to improve the potency and therapeutic index of antisense oligonucleotides while mitigating the hepatotoxicity associated with LNA. The key chemicals used in the synthesis include diacetone allofuranose, 2-bromomethyl naphthalene, tert-butyldiphenylsilyl chloride, and various nucleobases such as uracil, adenine, and guanine. The researchers employed a cycloetherification strategy to synthesize the cMOE and cEt nucleoside phosphoramidites, utilizing a 2-naphthylmethyl protecting group that provided crystalline intermediates and enabled clean deprotection under mild conditions. The biophysical evaluation revealed that cMOE- and cEt-containing oligonucleotides exhibited hybridization and mismatch discrimination attributes similar to LNA but with significantly improved resistance to exonuclease digestion. The study concludes that these modifications offer a promising approach for enhancing the stability and efficacy of antisense oligonucleotides, potentially leading to more effective and safer therapeutic applications.
10.1039/b717437c
The research investigates the one-electron oxidation of DNA duplex oligomers that do not contain guanine, focusing on the reactions at thymine bases. The purpose is to understand the mechanisms and products of oxidation in DNA sequences lacking guanine, which is typically the most reactive base in DNA oxidation. The study uses anthraquinone (AQ) as a photosensitizer linked to DNA oligomers to generate radical cations upon UVA irradiation. The key findings are that thymine, despite having a higher oxidation potential than adenine, is the primary site of oxidation reactions, leading to products such as thymidine glycols, 5-(hydroxymethyl)-2'-deoxyuridine, and 5-formyl-2'-deoxyuridine. 5-Hydroxymethyl-2'-deoxyuridine (5-HMdUrd) is formed through the reaction of the thymine radical cation with molecular oxygen (O2) after the initial deprotonation of the thymine methyl group. This process involves the formation of a transient 5-(2'-deoxyuridinyl)methyl radical, which is subsequently trapped by O2. 5-Formyl-2'-deoxyuridine (5-FormdUrd) is another product formed from the reaction of the thymine radical cation. Similar to 5-HMdUrd, its formation involves the initial deprotonation of the thymine methyl group, followed by reaction with molecular oxygen (O2). The research concludes that the reactivity of the thymine radical cation, rather than its stability, determines the oxidation products. The study also proposes a mechanism involving proton loss from the thymine methyl group or addition of H2O/O2 across the thymine double bond, which can initiate tandem reactions converting both thymines in a TT step to oxidation products. This work has implications for understanding oxidative damage in genomic DNA, particularly in sequences with few guanines.
10.1016/S0040-4039(00)89270-9
The research focuses on the one-step protection of the nucleoside ease in thymidine and uridine. The purpose of this study was to address the issue of unwanted side reactions that occur during the synthesis of oligonucleotides via the phosphotriester approach, particularly on the imide moieties of guanine, uracil, and thymine. The researchers aimed to protect these vulnerable positions by introducing a protecting group that could be selectively attached and later removed without causing damage to the nucleosides. The study concluded that 4-nitrophenylsulfonylethene (1) could be used for the selective protection of O' in the uracil or thymine residue in the corresponding unprotected nucleosides. The protecting group, 4-nitrophenylsulfonylethyl, was stable under various conditions but could be cleaved within 2.5 hours at 50-55°C by concentrated aqueous ammonia via β-elimination. Key chemicals used in this process included 4-nitrophenylsulfonyl ethene (1), thymidine (3), uridine (5), and tetrabutylammonium hydroxide as a catalyst. The researchers also used Dowex cation exchanger (H+-cycle) for purification and triethylamine for β-elimination. The protection and deprotection processes were confirmed through infrared spectra analysis and synthesis of the compounds via an alternative method, which yielded identical results.
10.1007/bf01169255
The study presents a novel method for synthesizing N2-substituted guanines, which are important in the creation of biologically active materials. The researchers used 2-chloro-7-benzylhypoxanthine as the starting material and reacted it with various amines, including primary and secondary aliphatic, aromatic, and alicyclic amines, to produce N2-substituted 7-benzylguanines. These intermediates were then subjected to palladium-catalyzed hydrogenation to remove the benzyl group, yielding the final N2-substituted guanines. The synthesized compounds include N2-methylguanine, N2-phenylguanine, and N2-dimethylguanine, among others. The method is advantageous due to the availability of starting materials and the relatively high yields of the final products, making it a potentially useful approach for the preparation of these biologically significant compounds.
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