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.bmcl.2015.10.025
The research focuses on the development of bioreductive deprotection of 4-nitrobenzyl groups on thymine bases in oligonucleotides to activate duplex formation, specifically targeting hypoxic cells which are characteristic of advanced solid tumors. The study synthesized oligonucleotides containing 4-O-(4-NO2-benzyl)thymine residues, which were unable to form stable duplexes under non-hypoxic conditions. However, under bioreductive conditions simulating hypoxia, the 4-nitrobenzyl groups were reduced, leading to the formation of stable duplexes with target oligonucleotides. Key reactants in the synthesis process included 4-O-sulfonylated intermediates, 4-NO2 benzyl alcohol, and 4,40-dimethoxytrityl chloride, among others, as detailed in Scheme 1 of the article. The purity and structure of the synthesized oligonucleotides were analyzed using high-performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectroscopy. The deprotection process was modeled using nitroreductase and NADH, with enzymatic reactions monitored by HPLC, and the hybridization properties of the protected and deprotected oligonucleotides were investigated through thermal denaturation experiments.
10.1021/jo962204x
This research study on the synthesis and conformational analysis of cyclohexane nucleosides, specifically focusing on 3-hydroxy-4-(hydroxymethyl)-1-cyclohexanyl purines and pyrimidines. The purpose of the study was to understand the correlation between the antiviral activity of these compounds and their conformational structure. The researchers synthesized the nucleosides using various nucleobases and ethyl 1,3-cyclohexadiene-1-carboxylate through a conjugated addition reaction and hydroboration of the cyclohexenyl precursor. Key chemicals used in the synthesis process included adenine, 2-amino-6-chloropurine, thymine, uracil, cytosine, and various protecting groups like monomethoxytrityl and trityl groups, as well as reagents such as DBU, TFA, and BH3-THF complex. The lack of antiviral activity observed in the synthesized compounds was linked to their conformation, which was deduced from NMR and X-ray analysis. The study concluded that the replacement of the ring oxygen with a methylene group in carbocyclic nucleosides led to a change in the preferred conformation of the nucleoside base from axial to equatorial, which might explain the loss of antiviral activity compared to anhydrohexitol nucleosides.
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.
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