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.
10.1248/cpb.51.1025
The study focuses on the design and synthesis of uracil-based heterocyclic compounds, which are significant in organic and medicinal chemistry due to their therapeutic potential and presence in natural products with strategic biological functions. The researchers synthesized various 6-methyluracil derivatives with different substituents at the 1-position, aiming to create new biologically active compounds. Key chemicals used include substituted ureas, diketene, and piperazine derivatives, which serve as starting materials and building blocks for the synthesis of the target uracil derivatives. The purpose of these chemicals is to create a range of compounds with potential pharmacological actions, such as antineoplastic, antihypertensive, anti-inflammatory, antiviral, and reverse transcriptase inhibitory effects. The study also details the synthetic strategies and confirms the structures of the synthesized compounds through analytical and spectroscopic data.
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.
10.1016/j.bmc.2008.05.013
The research focuses on the synthesis and evaluation of novel uracil nucleotide derivatives as agonists for the P2Y2 and P2Y6 receptors, which are G protein-coupled receptors activated by nucleotides. The study involves structural modifications of the phosphate, uracil, and ribose moieties of uracil nucleotides to assess their agonist activity at human P2Y2, P2Y4, and P2Y6 receptors. Key modifications include the 2-thio modification, phosphonomethylene bridges for stability, and truncation of dinucleotide agonists. The synthesized compounds were tested for their ability to activate phospholipase C (PLC) in human astrocytoma cells stably expressing the respective P2Y receptors. The experiments utilized various analytical techniques such as NMR, HPLC, and HRMS for compound identification and purity assessment. The main reactants included uracil nucleotides, phosphonic acids, and other chemical modifiers used to synthesize the novel derivatives. The analyses were conducted to determine the EC50 values of the compounds, reflecting their potency in stimulating PLC activity, and to explore structure-activity relationships (SARs).
10.1021/jo961806d
The research focuses on the stereoselective synthesis of branched and bicyclo 2′,3′-dideoxy-threo-furanosyl nucleosides from pyranoses, utilizing a ring contraction reaction as the key step. The purpose of this study is to develop methods for synthesizing these nucleosides, which are important due to their potential biological activities, including antitumor, antiviral, and antibacterial properties. The researchers successfully synthesized bicyclo nucleoside 21 and branched-chain nucleoside 26 from a common intermediate 14, which was derived from methyl 4,6-O-benzylidene-2-deoxy-3-O-triflyl-α-D-arabino-pyranoside (13). The synthesis involved the use of various chemicals, including electrophilic selenium and sulfur reagents, phenylthio derivative 20, and nucleoside bases such as uracil. The study concluded that the bicyclo and branched-chain threo-furanosyl nucleosides could be stereoselectively obtained through the ring contraction reaction and glycosylation, with the phenylselenenyl-induced glycosylation reaction showing a directing effect of the lactone group, preferentially forming the R anomer with the phenylselenenyl group on the endo face of the bicyclic compound. The research also demonstrated that two different glycosylation methods resulted in similar yields and stereoselectivities in the synthesis of branched nucleosides.
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