- Access to azolopyrimidine-6,7-diamines as a valuable “building-blocks” to develop new fused heteroaromatic systems
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A simple and convenient approach for the synthesis of new azolopyrimidine-6,7-diamines has been developed by the method of reductive cleavage of azo-group in series 6-[2-(4-methylphenyl)diazenyl]azolo[1,5-a]pyrimidine-7-amines, which was obtained by the interaction of aminoazoles with [2-(4-methylphenyl)hydrazinylidene]-3-oxo-propionitrile. The proposed approach allows to use a wide range of aminoazoles as a starting reagent and it also distinguishes itself by the simplicity of isolation and purification of products. The synthetic potential of presented diamines was demonstrated by the reaction of obtaining azolo[a]annulated pteridines.
- Gazizov, Denis A.,Fedotov, Victor V.,Chistyakov, Konstantin A.,Gorbunov, Evgeny B.,Rusinov, Gennady L.,Charushin, Valery N.
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- Synthesis and utilization of 13C(8)-enriched purines.
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A new and more efficient method is presented for the synthesis of 13C(8)-enriched adenine. In addition, we present for the first time the synthesis of 13C(8)-enriched 2-aminopurine and purine. All three analogues have been converted to the corresponding ribonucleosides. The adenine analogue has been further converted to the 2'-deoxy-nucleoside and incorporated into a synthetic oligonucleotide. Data is presented demonstrating the utility of 13C-enrichment in heteronuclear isotope-edited NMR spectra.
- LaFrancois,Fujimoto,Sowers
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- Prebiotic Origin of Pre-RNA Building Blocks in a Urea “Warm Little Pond” Scenario
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Urea appears to be a key intermediate of important prebiotic synthetic pathways. Concentrated pools of urea likely existed on the surface of the early Earth, as urea is synthesized in significant quantities from hydrogen cyanide or cyanamide (widely accepted prebiotic molecules), it has extremely high water solubility, and it can concentrate to form eutectics from aqueous solutions. We propose a model for the origin of a variety of canonical and non-canonical nucleobases, including some known to form supramolecular assemblies that contain Watson-Crick-like base pairs.The dual nucleophilic-electrophilic character of urea makes it an ideal precursor for the formation of nitrogenous heterocycles. We propose a model for the origin of a variety of canonical and noncanonical nucleobases, including some known to form supramolecular assemblies that contain Watson-Crick-like base pairs. These reactions involve urea condensation with other prebiotic molecules (e. g., malonic acid) that could be driven by environmental cycles (e. g., freezing/thawing, drying/wetting). The resulting heterocycle assemblies are compatible with the formation of nucleosides and, possibly, the chemical evolution of molecular precursors to RNA. We show that urea eutectics at moderate temperature represent a robust prebiotic source of nitrogenous heterocycles. The simplicity of these pathways, and their independence from specific or rare geological events, support the idea of urea being of fundamental importance to the prebiotic chemistry that gave rise to life on Earth.
- Menor Salván,Bouza, Marcos,Fialho, David M.,Burcar, Bradley T.,Fernández, Facundo M.,Hud, Nicholas V.
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p. 3504 - 3510
(2020/10/02)
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- Mapping the landscape of potentially primordial informational oligomers: (3′→2′)-D-phosphoglyceric acid linked acyclic oligonucleotides tagged with 2,4-disubstituted 5-aminopyrimidines as recognition elements
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The (3′→2′)-phosphodiester glyceric acid backbone containing an acyclic oligomer tagged with 2,4-disubstituted pyrimidines as alternative recognition elements have been synthesized. Strong cross-pairing of a 2,4-dioxo-5-aminopyrimidine hexamer, rivaling locked nucleic acid (LNA) and peptide nucleic acid (PNA), with complementary adenine-containing DNA and RNA sequences was observed. The corresponding 2,4-diamino- and 2-amino-4-oxo-5- aminopyrimidine-tagged oligomers were synthesized, but difficulties in deprotection, purification, and isolation thwarted further investigations. The acyclic phosphate backbone structure of the protected oligomer seems to be prone to an eliminative degradation owing to the acidic hydrogen at the 2′-position-an arrangement that renders the oligomer vulnerable to the conditions used for the removal of the protecting groups on the heterocyclic recognition element. However, the free oligomers seem to be stable under the conditions investigated. Prehistoric pairs: The (3′→2′)- phosphodiester glyceric acid backbone containing an acyclic oligomer tagged with 2,4-dioxo-5-aminopyrimidine pairs (see scheme) strongly with complementary adenine-containing DNA and RNA sequences. An eliminative degradation of the acyclic phosphate backbone owing to the acidic hydrogen at the 2′-position hampered studies of the corresponding 2,4-diamino- and 2-amino-4-oxo-5- aminopyrimidine series.
- Hernandez-Rodriguez, Marcos,Xie, Jian,Osornio, Yazmin M.,Krishnamurthy, Ramanarayanan
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supporting information; experimental part
p. 1252 - 1262
(2011/12/14)
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- Mapping the landscape of potentially primordial informational oligomers: Oligodipeptides tagged with 2,4-disubstituted 5-aminopyrimidines as recognition elements
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(Chemical Equation Presented) Bit different: 2,4-Dioxo- and 2,4-diamino-5-aminopyrimidine nuclei attached to an oligodipeptide backbone display a disparity in their base-pairing strength which is opposite to that shown by corresponding triazines. This behavior points to a remarkable correlation between pairing strength and ΔpKa values of pairs of complementary bases.
- Mittapalli, Gopi Kumar,Osornio, Yazmin M.,Guerrero, Miguel A.,Reddy, Kondreddi Ravinder,Krishnamurthy, Ramanarayanan,Eschenmoser, Albert
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p. 2478 - 2484
(2008/03/11)
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- Folate-Synthesizing Enzyme System as Target for Development of Inhibitors and Inhibitor Combinations against Candida albicans - Synthesis and Biological Activity of New 2,4-Diaminopyrimidines and 4′-Substituted 4-Aminodiphenyl Sulfones
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The paper describes the design, synthesis, and testing of inhibitors of folate-synthesizing enzymes and of whole cell cultures of Candida albicans. The target enzymes used were dihydropteroic acid synthase (SYN) and dihydrofolate reductase (DHFR). Several series of new 2,4-diaminopyrimidines were synthesized and tested as inhibitors of DHFR and compared with their activity against DHFR derived from mycobacteria and Escherichia coli. To test for selectivity, also rat DHFR was used. A series of substituted 4-aminodiphenyl sulfones was tested for inhibitory activity against SYN and the I50 values compared to those obtained previously against Plasmodium berghei- and E. coll-derived SYN. Surprisingly, QSAR equations show very similar structural dependencies. To find an explanation for the large difference in the I50 values observed for enzyme inhibition (SYN, DHFR) and for inhibition of cell cultures of Candida, mutant strains with overexpressed efflux pumps and strains in which such pumps are deleted were included in the study and the MICs compared. Efflux pumps were responsible for the low activity of some of the tested derivatives, others showed no increase in activity after pumps were knocked out. In this case it may be speculated that these derivatives are not able to enter the cells.
- Otzen, Thomas,Wempe, Ellen G.,Kunz, Brigitte,Bartels, Rainer,Lehwark-Yvetot, Gudrun,H?nsel, Wolfram,Schaper, Klaus-Jürgen,Seydel, Joachim K.
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p. 240 - 253
(2007/10/03)
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- Structure-Activity Relations. Part 12. Antibacterial Activity of a Series of 2,4-Diamino-6-substituted 5-(4-pyridylmethylamino)pyrimidines and 2,4-Diamino-5-(4-substituted benzylamino)pyrimidines.
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A series of 6-substituted 2,4-diamino-5-(4-pyridylamino)pyrimidines and of 2,4-diamino-5-(4-substituted benzylamino)pyrimidines has been prepared.Their antibacterial activity towards L. casei, S. aureus and E. coli has been investigated.These activities have been successfully correlated by Hansch-type relations.Dependence on both lipophilicity and electronic (polar) factors has been found.The results are related to the structure and interactions with the receptor.
- Bowden, Keith,Bright, Andrew C.
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p. 514 - 539
(2007/10/02)
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