-
The Journal of Organic Chemistry Jul 2022Functionalized nucleosides bearing pyrimidine or purine bases can be prepared by activation of accessible pyrimidine nucleosides and subsequent transglycosylation....
Functionalized nucleosides bearing pyrimidine or purine bases can be prepared by activation of accessible pyrimidine nucleosides and subsequent transglycosylation. Nitration of lumicitabine, a 2'-fluoro-2'-deoxycytidine class antiviral agent, and its 2'-fluoro-2'-deoxyuridine precursor produce the same 5-nitro-2'-fluoro-2'-deoxyuridine. Under Vorbrüggen conditions, 5-nitrouracil serves as the leaving nucleobase and enables exchange with pyrimidine and purine nucleobases to anomeric 2'-fluoro-2'-deoxyribonucleosides in favor of β-anomers generally. The strategy is also applied in the isotopic labeling of 2'-fluoro-2'-deoxyuridines.
Topics: Antiviral Agents; Deoxyribonucleosides; Deoxyuridine; Purines; Pyrimidine Nucleosides
PubMed: 35759615
DOI: 10.1021/acs.joc.2c01093 -
Nucleosides, Nucleotides & Nucleic Acids 2023To assess the feasibility of high-temperature aminolysis of deoxyribooligonucleotides containing rare bases as a method to determine their base sequence, the...
To assess the feasibility of high-temperature aminolysis of deoxyribooligonucleotides containing rare bases as a method to determine their base sequence, the 2'-βD-deoxyribosides of 5-bromouracil, 2-aminopurine, uracil, adenine, cytosine, 5-methylcytosine, hypoxanthine, N-methyladenine, N-ethylcytosine, and guanine were compared as to their rate of degradation in 0.5 M aqueous pyrrolidine at 110 °C, conditions used earlier in the analysis of oligonucleotides containing only the canonical bases. The reaction mixtures were analyzed by chromatography on Zorbax XDB-CN and UV absorption spectroscopy. The first-order rate constants for the nucleoside degradations decreased in the above order, spanning a wide range of reactivities. Some of these nucleosides were also tested in 0.5 M aqueous ammonia at 110 °C, giving similar first-order rate constants, except for 2'-deoxyguanosine, which is much more reactive with ammonia, due to the lower basicity of this reagent, leaving a larger proportion of the nucleoside in the non-ionized form, susceptible to nucleophilic attack at the base. Short oligothymidylates containing a single 2-aminopurine, adenine, guanine, or cytosine unit in central position were tested in pyrrolidinolysis, to determine the cleavage rates at these sites and the dependence of these cleavage rates on oligonucleotide length. A model decadeoxyribonucleotide containing all four canonical bases was also pyrrolidinolyzed, followed by ion-exchange chromatography, to deduce the nucleotide sequence from the resulting chromatographic profile.
Topics: Deoxyribonucleosides; Oligodeoxyribonucleotides; Solvents; Sequence Analysis, DNA; Kinetics
PubMed: 37165577
DOI: 10.1080/15257770.2023.2209135 -
Pharmacology & Therapeutics 1979
Review
Topics: Animals; Antineoplastic Agents; Antiviral Agents; Deoxycytidine; Humans; Idoxuridine; Tetrahydrouridine; Virus Activation; Virus Replication
PubMed: 392550
DOI: 10.1016/0163-7258(79)90023-8 -
The Journal of Organic Chemistry Dec 2018The preparation of 2-deoxy-l-ribose derivatives or mirror image deoxyribonucleosides (l-deoxyribonucleosides) from d-ribose is reported. Starting from inexpensive...
The preparation of 2-deoxy-l-ribose derivatives or mirror image deoxyribonucleosides (l-deoxyribonucleosides) from d-ribose is reported. Starting from inexpensive d-ribose, an acyclic d-form carbohydrate precursor was synthesized to study a unique carbonyl translocation process. In this novel radical reaction, not only was the configuration of the sugar transformed from the d-form to the l-form, but also deoxygenation at the C(2) position of the sugar was successfully achieved. This is one of the most practical methods for converting a d-sugar to a 2-deoxy-l-sugar in a one-step reaction. To further identify the reaction product, radical reactions followed by treatment with 1,3-propanedithiol and then benzoylation were performed to afford a dithioacetal derivative. The stereochemistry and configuration of the 2-deoxy-l-ribose dithioacetal derivative were confirmed by its X-ray crystal structure. To further apply this methodology, a diethyl thioacetal derivative was formed, followed by selective benzoyl protection, and an NIS-initiated cyclization reaction to give the desired ethyl S-l-2-deoxyriboside, which can be used as a 2-deoxy-l-ribosyl synthon in the formal total synthesis of various l-deoxyribonucleosides, such as l-dT.
Topics: Chemistry Techniques, Synthetic; Cyclization; Deoxyribonucleosides; Ribose; Stereoisomerism
PubMed: 30474372
DOI: 10.1021/acs.joc.8b02002 -
Nucleosides, Nucleotides & Nucleic Acids 2014Deoxyribonucleoside kinases phosphorylate deoxyribonucleosides into the corresponding 5'-monophosphate deoxyribonucleosides to supply the cell with nucleic acid...
Deoxyribonucleoside kinases phosphorylate deoxyribonucleosides into the corresponding 5'-monophosphate deoxyribonucleosides to supply the cell with nucleic acid precursors. In mitochondrial fractions of the model plant Arabidopsis thaliana, we detected deoxyadenosine and thymidine kinase activities, while the cytosol fraction contained six-fold lower activity and chloroplasts contained no measurable activities. In addition, a mitochondrial fraction isolated from the potato Solanum tuberosum contained thymidine kinase and deoxyadenosine kinase activities. We conclude that an active salvage of deoxyribonucleosides in plants takes place in their mitochondria. In general, the observed localization of the plant dNK activities in the mitochondrion suggests that plants have a different organization of the deoxyribonucleoside salvage compared to mammals.
Topics: Arabidopsis; DNA, Plant; Deoxyribonucleosides; Intracellular Space; Mitochondria; Phosphotransferases (Alcohol Group Acceptor); Protein Transport; Solanum tuberosum; Thymidine Kinase
PubMed: 24940682
DOI: 10.1080/15257770.2013.853782 -
Nucleosides, Nucleotides & Nucleic Acids 2019Degradation of 2'-deoxyribonucleosides in 0.5 M aqueous pyrrolidine at 110 °C proceeds at different rates, ordered as...
Degradation of 2'-deoxyribonucleosides in 0.5 M aqueous pyrrolidine at 110 °C proceeds at different rates, ordered as deoxyuridine > deoxyadenosine > deoxycytidine > deoxyguanosine ≫ deoxythymidine. Deoxyadenosine degradation produces the free base, adenine, while deoxycytidine by deamination produces deoxyuridine, and then uracil. The solvolysis of deoxyadenosine has an activation energy of 23.3 kcal/mol. Ammonolysis is slower than pyrrolidinolysis for deoxyadenosine, but faster for deoxyguanosine. In pyrrolidinolysis of the trinucleotides, d-TGT and d-TAT, the guanine moiety reacts faster than the adenine moiety. These trends are interpreted in terms of the ionization of the guanine moieties under basic conditions, rendering them less susceptible to nucleophilic attack.
Topics: Amines; Deoxyribonucleosides; Heterocyclic Compounds; Hot Temperature; Kinetics; Solvents; Thermodynamics; Water
PubMed: 30942138
DOI: 10.1080/15257770.2019.1597111 -
Current Protocols in Nucleic Acid... May 2001The detailed preparation of deoxyribonucleoside phosphoramidites bearing a 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl group for P(III) protection is presented. The...
The detailed preparation of deoxyribonucleoside phosphoramidites bearing a 4-[N-methyl-N-(2,2,2-trifluoroacetyl)amino]butyl group for P(III) protection is presented. The use of this group circumvents nucleobase alkylation during oligonucleotide deprotection. Two syntheses of phosphoramidites starting from either a phosphordichloridite precursor or a bis-(N,N-diisopropylamino)chlorophosphine intermediate are described for the phosphinylation of suitably protected deoxyribonucleosides.
Topics: 1-Butanol; Biochemistry; Deoxyribonucleosides; Oligodeoxyribonucleotides; Organophosphorus Compounds
PubMed: 18428840
DOI: 10.1002/0471142700.nc0207s04 -
PloS One 2016In this study, several RNA polymerases were used for the first time to examine the possibility of transcriptional incorporation of 5'-N-triphosphates of...
In this study, several RNA polymerases were used for the first time to examine the possibility of transcriptional incorporation of 5'-N-triphosphates of 5'-amino-5'-deoxyribonucleosides (5'NH NTPs). The T3, T7, Sp6 and T7 Y639F RNA polymerases were employed to show that the full-length transcript cannot be synthesized. The results suggest that the application of 5'NH NTPs could decrease transcription reaction rates. What is more, the modification of transcription conditions had no influence on the rate of 5'NH NTPs incorporation. Based on experimental data it is postulated that 5'NH NTPs can be used as potential transcription inhibitors. Our findings expand the knowledge on suitable uses of the 5'-N-triphosphates of 5'-amino-5'-deoxyribonucleoside and the exact mechanism of transcriptional inhibition.
Topics: DNA-Directed RNA Polymerases; Deoxyribonucleosides; RNA; Transcription, Genetic
PubMed: 26829482
DOI: 10.1371/journal.pone.0148282 -
Nucleosides, Nucleotides & Nucleic Acids 2001A unique series of simple unnatural L-nucleosides that specifically inhibit hepatitis B virus (HBV) replication has been discovered. These molecules have in common a... (Review)
Review
A unique series of simple unnatural L-nucleosides that specifically inhibit hepatitis B virus (HBV) replication has been discovered. These molecules have in common a hydroxyl group in the 3'-position (3'-OH) of the beta-L-2'-deoxyribose sugar that confers antiviral activity specifically against hepadnaviruses. Replacement of the 3'-OH broadens activity to other viruses. Substitution in the base decreases antiviral potency and selectivity. Human DNA polymerases and mitochondrial function are not effected. Plasma viremia is reduced up to 8 logs in a woodchuck model of chronic HBV infection. These investigational drugs, used alone or in combination, are expected to offer new therapeutic options for patients with chronic HBV infection.
Topics: Animals; Antiviral Agents; Deoxyadenosines; Deoxycytidine; Deoxyribonucleosides; Hepatitis B Virus, Woodchuck; Hepatitis B virus; Hepatitis B, Chronic; Humans; Structure-Activity Relationship; Substrate Specificity; Thymidine; Virus Replication
PubMed: 11563077
DOI: 10.1081/NCN-100002336 -
Nucleosides, Nucleotides & Nucleic Acids Mar 2017Reported is an efficient synthesis of adenyl and uridyl 5'-tetrachlorophthalimido-5'-deoxyribonucleosides, and guanylyl 5'-azido-5'-deoxyribonucleosides, which are...
Reported is an efficient synthesis of adenyl and uridyl 5'-tetrachlorophthalimido-5'-deoxyribonucleosides, and guanylyl 5'-azido-5'-deoxyribonucleosides, which are useful in solid-phase synthesis of phosphoramidate and ribonucleic guanidine oligonucleotides. Replacement of 5'-hydroxyl with tetrachlorophthalimido group was performed via Mitsunobu reaction for adenosine and uridine. An alternative method was applied for guanosine which replaced the 5'-hydroxyl with an azido group. The resulting compounds were converted to 5'-amino-5'-deoxyribonucleosides for oligonucleotide synthesis. Synthetic intermediates were tested as antimicrobials against six bacterial strains. All analogs containing the 2',3'-O-isopropylidine protecting group demonstrated antibacterial activity against Neisseria meningitidis, and among those analogs with 5'-tetrachlorophthalimido and 5'-azido demonstrated increased antibacterial effect.
Topics: Adenosine; Anti-Bacterial Agents; Azides; Chemistry Techniques, Synthetic; Deoxyribonucleosides; Drug Evaluation, Preclinical; Microbial Sensitivity Tests; Neisseria meningitidis; Phthalimides; Uridine
PubMed: 28045593
DOI: 10.1080/15257770.2016.1250906