10.1002/chem.201902411
The research focuses on the chemical synthesis of an oligoribonucleotide (ASL of tRNALys T. brucei) that contains a recently discovered cyclic form of 2-methylthio-N6-threonylcarbamoyladenosine (ms2ct6A). The team developed a method for synthesizing the protected form of ms2t6A from adenosine or guanosine using an optimized carbamate method and, for the first time, the isocyanate route. They then transformed the hypermodified nucleoside into a protected ms2t6A-phosphoramidite monomer, which was used to synthesize a 17-nucleotide precursor oligonucleotide. The key experiment involved a stereochemically secure cyclization of ms2t6A to ms2ct6A at the oligonucleotide level, yielding an oligonucleotide bearing the ms2ct6A unit. The synthesized oligonucleotides were analyzed using techniques such as RP-HPLC, MALDI-TOF MS, and nucleoside composition analysis to confirm their structures and purities. This research provides a method for producing oligonucleotides suitable for studying the structure-activity relationships of tRNA modifications.
10.1021/jo702023s
The research focuses on the copper(I)-catalyzed [3+2] cycloaddition of nucleosides and nucleotides to synthesize oligonucleotide dimers and conjugates with near-quantitative yield. The experiments involved the preparation of 2′-azide or 2′-acetylene modified adenosines as building blocks for the mild and efficient synthesis of oligonucleotide hetero- and homoconjugates. Reactants included adenosine, sodium hydride, alkyl chlorides, and various azides and acetylenes, which were subjected to cycloaddition reactions under different conditions to optimize the process. The analyses used to characterize the synthesized compounds included 1H and 13C NMR spectroscopy, high-resolution mass spectrometry (HRMS), and MALDI-TOF mass spectrometry, as well as high-performance liquid chromatography (HPLC) to monitor the reaction progress and confirm the formation of the desired triazole-linked conjugates.
10.1016/S0040-4020(97)00313-X
The research study on the efficient removal of sugar O-Tosyl groups and heterocyclic halogens from purine nucleosides using sodium naphthalenide. The purpose of this research was to develop an improved strategy for the synthesis of specific nucleosides by leveraging the high reduction potential of sodium naphthalenide, which is known for its ability to cleave carbon-halogen bonds and regenerate alcohols and amines from p-toluenesulfonate esters and p-toluenesulfonamides. The study concluded that sodium naphthalenide could effectively remove 2'-, 3'-, and 5'-O-tosyl groups from the sugar moiety of nucleosides, making p-toluenesulfonyl a viable protecting group. Additionally, it demonstrated the reductive cleavage of bromo or chloro groups from the 2-, 6-, or 8-position of purine nucleosides. Key chemicals used in the process included sodium naphthalenide, p-toluenesulfonate esters, p-toluenesulfonamides, and various purine nucleosides such as adenosine and its derivatives.
10.1016/j.bmcl.2005.07.052
The research focuses on the synthesis of [1,2,4]triazolo[1,5-a]pyrazines as potential adenosine A2A receptor antagonists, which are of interest due to their therapeutic potential in treating Parkinson's disease. The purpose of the study was to develop selective A2A antagonists that could improve target affinity, selectivity, and in vivo activity, potentially offering a means to control immunological, cardiovascular, renal, or neurological responses for therapeutic benefit. The researchers synthesized a series of these antagonists using a novel route, starting from 2-amino-3,5-dibromopyrazine (7) and employing oxidative cyclization with reagents such as AlCl3 and Pb(OAc)4 to form the [1,2,4]triazolo[1,5-a]pyrazine nucleus.
10.1021/jm00401a018
The research aims to develop more selective A1 adenosine receptor agonists by synthesizing and evaluating a series of 1-deaza analogues of adenosine derivatives. The study synthesized compounds such as p-[(R)-(-)-1-methyl-2-phenethyl]-1-deazaadenosine (1-deaza,R-PIA, 3a), NG-cyclopentyl-1-deazaadenosine (1-deazaCPA, 3b), NG-cyclohexyl-1-deazaadenosine (1-deazaCHA, 3c), and their 2-chloro derivatives, as well as N-ethyl-1'-deoxy-1'-(1-deaza-6-amino-9H-purin-9-yl)-β-D-ribofuranuronamide (1-deazaNECA, 10). The biological evaluation of these compounds in adenylate cyclase and radioligand binding studies revealed that 1-deazaNECA (10) is a nonselective agonist at both A1 and A2 adenosine receptors, being about 10-fold less active than NECA but more active than 1-deazaadenosine. The N6-substituted 1-deazaadenosines largely retain A1 agonist activity but lose some A2 agonist activity, resulting in A1-selective compounds, with p-cyclopentyl-2-chloro-1-deazaadenosine (1-deaza-2-Cl-CPA, 2b) identified as the most selective A1 agonist. The study concludes that the presence of the nitrogen atom at position 1 of the purine ring is not critical for A1 receptor-mediated adenosine actions.
10.1021/jm00121a016
The study primarily focuses on the synthesis and evaluation of various nucleoside analogues as potential anti-HIV agents. The researchers synthesized a series of 1',2'-seco-dideoxynucleosides, including cytidine (12), guanosine (14), adenosine (16), and inosine (18) analogues, starting from (R)-benzylglycidol. These compounds were prepared through a series of chemical reactions involving epoxidation, alkylation, and debenzylations. The synthesized compounds were then tested for their antiviral activity against HIV-1 in ATH8 cells and their cytotoxicity in uninfected human PBM cells. Additionally, the study also evaluated the compounds for activity against HSV-1 and HSV-2 using plaque reduction assays in Vero cells. The results indicated that these nucleoside analogues did not show significant antiviral activity against HIV-1 compared to the reference compound ddAdo. The study provides insights into the chemical synthesis of these nucleoside analogues and their potential as antiviral agents, highlighting the importance of further research to optimize their structures for enhanced activity.
10.1080/15257779408012148
The research aimed to devise a new method for the debenzylation of N6-benzyladenosines, which is crucial for the convenient synthesis of [6-15N]-labeled adenosines. The purpose of this research was to develop a synthetic route to 15N-labeled nucleosides, which are valuable for studying nucleic acid structures, drug bindings, and nucleotide-protein interactions. The researchers concluded that the most effective method involved the oxidation of N6-benzyladenosines with ammonium peroxydisulfate in a pH 7.2 buffer solution, which provided a simple and high-yield procedure for obtaining [6-15N]-labeled adenosines from inosines without the need to protect the sugar moiety.
