56-06-4Relevant articles and documents
Prebiotic Origin of Pre-RNA Building Blocks in a Urea “Warm Little Pond” Scenario
Menor Salván,Bouza, Marcos,Fialho, David M.,Burcar, Bradley T.,Fernández, Facundo M.,Hud, Nicholas V.
, p. 3504 - 3510 (2020/10/02)
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.
Design, synthesis and biological evaluation of pyrimidine-based derivatives as antitumor agents
AlHazmi, Hassan A.,Albratty, Mohammed M.,El-Sharkawy, Karam A.
, p. 227 - 238 (2020/10/06)
In this paper we made a contentious effort to afford heterocyclic compounds with interesting biological activities. The reaction of guanidine with either activated methylene groups, arylhydrazono derivatives, dicyanopropene derivatives, malononitrile dimer or arylhydarazononitrile derivatives afforded diaminopyrimidine derivatives, aryldiazenyl pyrimidine derivatives, fused pyridopyrimidne derivatives and pyrimidopyridazine derivatives respectively. Also the reaction of guanidine with phenylhydrazono carbonyl compounds produced phenyldiazenyl pyrimidine derivatives. The latter products were directed toward the reaction with either acetic anhydride or ethylcyanoacetate to form acetamidopyrimidine derivatives and cyanoacetamidopyrimidine derivatives respectively. The latter products underwent cyclization via reaction with either activated methylene groups or activated methylene carbonyl compounds afforded pyridopyrimidne derivatives. The structures of the newly synthesized compounds were established using IR, 1H NMR, 13C NMR and mass spectrometry and their antitumor activity was investigated. Some of these compounds showed promising inhibitory effects on the three different cell lines.
Method for preparing folic acid by virtue of micro-channel reaction (by machine translation)
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Paragraph 0053-0056, (2020/12/14)
The invention belongs to the technical field of chemical synthesis of drugs, and relates to a synthesis method for preparing folic acid through a microchannel reactor. An intermediate 6 is prepared from cyanoethyl acetate as a raw material by one-step continuous operation, and the folic acid bulk drug is prepared through one-step reaction of the intermediate 6 and L - glutamate. The synthesis method uses the microchannel reactor to prepare the folic acid intermediate 2,triamino -4 - hydroxypyrimidine and folic acid, is safe and environment-friendly, and ensures the tasteless system. The method guarantees that the operation is simple and feasible, the solvent consumption is greatly reduced, 2,triamino -4 - hydroxyl pyrimidine yield and purity are obviously improved. (by machine translation)
Silica Metal Oxide Vesicles Catalyze Comprehensive Prebiotic Chemistry
Mattia Bizzarri, Bruno,Botta, Lorenzo,Pérez-Valverde, Maritza Iveth,Saladino, Raffaele,Di Mauro, Ernesto,García-Ruiz, Juan Manuel
, p. 8126 - 8132 (2018/05/29)
It has recently been demonstrated that mineral self-assembled structures catalyzing prebiotic chemical reactions may form in natural waters derived from serpentinization, a geological process widespread in the early stages of Earth-like planets. We have s
Method for synthesizing 2,4-diamino-6-chloropyrimidine
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Paragraph 0032; 0033; 0034; 0035, (2018/04/21)
The invention discloses a method for synthesizing 2,4-diamino-6-chloropyrimidine. According to the method, methyl cyanoacetate, guanidine nitrate and sodium methoxide serve as raw materials to react with one another to obtain 2,4-diamino-6-hydroxypyrimidine, and then 2,4-diamino-6-hydroxypyrimidine is chloridized with POCl3 in the presence of triethylamine to obtain 2,4-diamino-6-chloropyrimidine.Compared with the prior art, the situation that the whole reactant is neutralized to generate and precipitate a large amount of phosphate is avoided, the product purity is improved, the product yieldis increased, the situation that a solvent is used for refining DACP is avoided, the process is greatly simplified, the cost is reduced, the yield is increased, and the method has the advantages of being high in yield, easy to operate and high in safety and is a very effective process suitable for industrialized mass production.
A Global Scale Scenario for Prebiotic Chemistry: Silica-Based Self-Assembled Mineral Structures and Formamide
Saladino, Raffaele,Botta, Giorgia,Bizzarri, Bruno Mattia,Di Mauro, Ernesto,Garcia Ruiz, Juan Manuel
, p. 2806 - 2811 (2016/06/01)
The pathway from simple abiotically made organic compounds to the molecular bricks of life, as we know it, is unknown. The most efficient geological abiotic route to organic compounds results from the aqueous dissolution of olivine, a reaction known as serpentinization (Sleep, N.H., et al. (2004) Proc. Natl. Acad. Sci. USA 101, 12818-12822). In addition to molecular hydrogen and a reducing environment, serpentinization reactions lead to high-pH alkaline brines that can become easily enriched in silica. Under these chemical conditions, the formation of self-assembled nanocrystalline mineral composites, namely silica/carbonate biomorphs and metal silicate hydrate (MSH) tubular membranes (silica gardens), is unavoidable (Kellermeier, M., et al. In Methods in Enzymology, Research Methods in Biomineralization Science (De Yoreo, J., Ed.) Vol. 532, pp 225-256, Academic Press, Burlington, MA). The osmotically driven membranous structures have remarkable catalytic properties that could be operating in the reducing organic-rich chemical pot in which they form. Among one-carbon compounds, formamide (NH2CHO) has been shown to trigger the formation of complex prebiotic molecules under mineral-driven catalytic conditions (Saladino, R., et al. (2001) Biorganic & Medicinal Chemistry, 9, 1249-1253), proton irradiation (Saladino, R., et al. (2015) Proc. Natl. Acad. Sci. USA, 112, 2746-2755), and laser-induced dielectric breakdown (Ferus, M., et al. (2015) Proc Natl Acad Sci USA, 112, 657-662). Here, we show that MSH membranes are catalysts for the condensation of NH2CHO, yielding prebiotically relevant compounds, including carboxylic acids, amino acids, and nucleobases. Membranes formed by the reaction of alkaline (pH 12) sodium silicate solutions with MgSO4 and Fe2(SO4)3·9H2O show the highest efficiency, while reactions with CuCl2·2H2O, ZnCl2, FeCl2·4H2O, and MnCl2·4H2O showed lower reactivities. The collections of compounds forming inside and outside the tubular membrane are clearly specific, demonstrating that the mineral self-assembled membranes at the same time create space compartmentalization and selective catalysis of the synthesis of relevant compounds. Rather than requiring odd local conditions, the prebiotic organic chemistry scenario for the origin of life appears to be common at a universal scale and, most probably, earlier than ever thought for our planet.
IKK-β as target to 2-acetyl-8-substituted guanine derivatives, application and its preparation method (by machine translation)
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Paragraph 0017, (2017/03/28)
The present invention discloses a target IKK-β to 2-acetyl-8-substituted guanine derivatives, application and its preparation method, the compounds of the present invention to the A549 cell inhibitory activity, the increase of the density of the as to, its rate will also increase, however, the kind of compound, to b16-f10, H460 and U251 cell strain basic noec role, this kind of selectivity for inhibition of specific anti-tumor medicament as the same is of special significance. (by machine translation)
Inhibition of human O6-alkylguanine-DNA alkyltransferase and potentiation of the cytotoxicity of chloroethylnitrosourea by 4(6)- (benzyloxy)-2,6(4)-diamino-5-(nitro or nitroso)pyrimidine derivatives and analogues
Terashima, Isamu,Kohda, Kohfuku
, p. 503 - 508 (2007/10/03)
A series of 4(6)-(benzyloxy)-2,6(4)-diamino-5-(nitro or nitroso)pyrimidine derivatives and analogues of which 4(6)-benzyloxy groups were replaced with a (2-, 3-, or 4-fluorobenzyl)oxy or (2-, 3-, or 4- pyridylmethyl)oxy group, was synthesized. The abilities of these compounds to inhibit human O6-alkylguanine-DNA alkyltransferase (AGAT) in vitro and to potentiate the cytotoxicity of 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3- (2-chloroethyl)-3-nitrosourea (ACNU) toward HeLa S3 cells were evaluated. 2,4-Diamino-6-[(2-fluorobenzyl)oxy]-5-nitropyrimidine (3) and 2,4-diamino-5- nitro-6-(2-pyridylmethoxy)pyrimidine (6), whose ortho positions of the 6- substituent are modified, were much weaker in terms of these abilities than the corresponding meta- or para-modified compounds. These results are consistent with those of our previous study using a series of O6- benzylguanine derivatives. All 5-nitrosopyrimidine derivatives examined exerted both stronger AGAT-inhibition and ACNU-enhancement abilities than the corresponding 5-nitro derivatives. Among a variety of compounds that we have examined to date, 2,4-diamino-6-[(4-fluorobenzyl)oxy]-5-nitrosopyrimidine (10) exhibited the strongest ability to inhibit AGAT, and its magnitude was 2.5 and 50 times those of 4-(benzyloxy)-2,6-diamino-5-nitrosopyrimidine (9) and O6-benzylguanine (1), respectively. A strong positive correlation was observed between the ability to inhibit AGAT and to potentiate the cytotoxicity of ACNU. This strongly indicates that 4(6)-(benzyloxy)pyrimidine derivatives and their analogues potentiate ACNU cytotoxicity by inhibiting AGAT activity. To characterize the reactivity of test compounds, alkyl- transfer reactions were also carried out using the biomimetic alkyl-transfer system.
Hydrolytic Stability of Ammo-substituted Difluoropyrimidines
Popova,Studentsov
, p. 435 - 438 (2007/10/03)
Hydrolytic stability of a series of amino-substituted difluoropyrimidines in the pH range 1.4-12.5 at 20°C is studied. The rate constants of aklaline hydrolysis at pH 12.5 are determined, and the effect of substituents in the heterocycle on the rate of alkaline hydrolysis is demonstrated.
Decarbonylation of Some Pyrimidine-5-carboxaldehydes
Delia, Thomas J.,Polenz, Barry,Martin, Mary C.
, p. 1697 - 1700 (2007/10/02)
In the course of determining the ultraviolet spectra of some 2,4,6-trisubstituted-pyrimidine-5-carboxaldehydes we discovered the facile loss of the formyl group.The reaction appears to be restricted to pyrimidine-5-carboxaldehydes containing three strongly electron donating substituents.Loss of the formyl group occurs at room temperature only in methanol with large excess of acid.Other alcohols and water fail to afford the decarbonylated product.A suggested pathway for this reaction is offered.
