An improved microbial synthesis of purine nucleosides

E. coliBL21 synthesized purine nucleosides from pyrimidine ones. A 94% yield of adenosine from uridine was reached within 1 h.     

A Versatile Synthesis of Dihydropyrimidinone C‐Nucleosides

A versatile synthesis of N‐substituted dihydropyrimidinone C‐nucleosides (20–29) is described. Glycosyl amino esters (3–9), obtained by reductive alkylation of glycosyl amino esters 1 and 2, on condensation with different isocyanates afforded respective ureido derivatives (10–19) in good to quantitative yields. The latter on cyclative amidation with a combination of DBU/TBAB (tetrabutylammonium bromide)/4Å molecular sieve gave the corresponding nucleosides (20–29) in good yields.     

N6-methyladenosine (m6A) is an endogenous A3 adenosine receptor ligand

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Solid-phase Parallel Synthesis of 4-β-D-Ribofuranosylpyrazolo[4,3-d]pyrimidine Nucleosides

The synthesis of pyrazolo[4,3-d]pyrimidine nucleoside library using solid-phase parallel synthesis methodology is described. Glycosylation of the trimethylsilyl (TMS) derivative of 1- and 2-(methyl)-1H and 2H-pyrazolo[4,3-d]pyrimidine-5,7-(4H,6H)-dione (5) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of TMS triflate provided two novel protected nucleosides 6 and 7. The structures of 6 and 7 were assigned by 1H and 2D NMR experiments. Nucleosides 6 and 7 were then transformed to the key intermediates 12 and 15 respectively. Reaction of 12 and 15 with MMTCl resin in the presence of 2,6-lutidine afforded the necessary scaffolds B and C. Different amines (96) were introduced selectively by nucleophilic substitution on scaffolds B and C using solid-phase parallel semi-automated synthesizer. Cleavage of the products from the solid support with 30% HFIP in a parallel fashion yielded nucleoside libraries simultaneously, and they were analyzed and characterized by high-throughput LC-MS.     

Synthesis and NMR Assignment of the Two Diastereomers of 8,6′-Cyclo-2′,6′-Dideoxyadenosine

We herein present the first synthesis and characterization of the two C5′ diastereomers of 8,6′-cyclo-2′,6′-dideoxyadenosine. Starting from commercially available 2′-deoxyadenosine, the target cyclonucleosides were synthesized in 11 linear steps. Following a zinc-mediated cyclization reaction to form the seven-membered ring, the stereochemistry of the newly formed chiral center was established using two-dimensional NOESY NMR experiments.

[Supplemental materials are available for this article. Go to the publisher's online edition of Nucleosides, Nucleotides & Nucleic Acids for the free supplemental resource.]     

Novel 5-Arylcarbamoyl-2-methylisoxazolidin-3-yl-3-phosphonates as Nucleotide Analogues

A series of 5-substituted 3-phosphonylated isoxazolidines have been obtained via cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N-heteroaromatic acrylamides. Good trans/cis diastereoselectivities (d.e. 58–76%) of isomeric (3-diethoxyphosphoryl)isoxazolidines were observed. cis- and trans-Isoxazolidine phosphonates were evaluated for their antiviral activity against a broad range of DNA and RNA viruses but were found inactive. Their cytostatic activity toward L1210, CEM, and HeLa cells was also established, and compounds cis-12r and trans-11r having a 2,2-difluorobenzo[d][1,3]dioxole moiety slightly inhibited proliferation of HeLa cells at IC₅₀ values of 186 and 179 μM, respectively.     

Synthesis of the first example of a nucleoside analogue bearing a 5′-deoxy-β-d-allo-septanose as a seven-membered ring sugar moiety

The first example of a nucleoside analogue bearing a 5′-deoxy-β-d-allo-septanose as a seven-membered ring sugar moiety, namely 9-(5-deoxy-β-d-allo-septanosyl)-adenine, is reported. This compound was synthesized in 14 steps from the commercially available d-glycero-d-gulo-1,4-lactone. When evaluated in cell culture experiments against a broad range of viruses, it did not exhibit any significant antiviral effect or cytotoxicity.     

New carbocyclic nucleoside analogues with a bicyclo[2.2.1]heptane fragment as sugar moiety; Synthesis,X-ray crystallography and anticancer activity

An amine group was synthesized starting from an optically active bicyclo[2.2.1]heptane compound, which was then used to build the 5 atoms ring of a key 6-chloropurine intermediate. This was then reacted with ammonia and selected amines obtaining new adenine- and 6-substituted adenine conformationally constrained carbocyclic nucleoside analogues with a bicyclo[2.2.1]heptane skeleton in the sugar moiety. X-ray crystallography confirmed an exo-coupling of base to the ring and a L configuration of the nucleoside analogues. The compounds were tested for anticancer activity.     

Synthesis and antiviral activities of 3-deaza-3-fluoroaristeromycin and its 5′ analogues

The naturally occurring adenine based carbocyclic nucleosides aristeromycin and neplanocin A and their 3-deaza analogues have found a prominent place in the search for diverse antiviral activity agent scaffolds because of their ability to inhibit S-adenosylhomocysteine (AdoHcy) hydrolase. Following the lead of these compounds, their 3-deaza-3-fluoroaristeromycin analogues have been synthesized and their effect on S-adenosylhomocysteine hydrolase and RNA and DNA viruses determined.     

Investigation of riboflavin sensitized degradation of purine and pyrimidine derivatives of DNA and RNA under UVA and UVB

DNA and RNA undergo photodegradation in UVC (200-290 nm) due to direct absorption by the purine and pyrimidine bases. Limited effects are observed under UVB (290-320 nm) or UVA (320-400 nm). We have observed that an endogenous photosensitizer, riboflavin (RF), upon exposure to UVB or UVA can extensively damage the DNA and RNA bases. Guanine, uracil, thymine, adenine and cytosine were degraded by 100%, 82%, 60.4%, 46.3% and 10.3% under UVA (12 J) and by 100%, 54.1%, 38.9%, 42.2% and <1.0% under UVB (6 J), respectively. Guanosine and deoxyguanosine were degraded by 98 ± 1.0% and 80 ± 1.0% under UVA (4 J) and UVB (12 J), respectively. With an exception of GMP (53-82%), dGMP (51-88%) and to some extent TMP (3-4%) the remaining nucleosides and nucleotides were resistant to RF-induced photodecomposition. The photodegradation of G derivatives by RF was 2-fold higher than a well known photodynamic agent rose bengal. A comparison of the intensities of UVA and UVB sources used in this study with natural sunlight suggests that exposure with the latter along with an endogenous photosensitizer can have similar effects on DNA and RNA depending upon the duration of exposure.