71-30-7Relevant articles and documents
A facile and effective synthesis of lamivudine 5′-diphosphate
Roy, Béatrice,Lefebvre, Isabelle,Puy, Jean-Yves,Périgaud, Christian
, p. 1250 - 1252 (2011)
We report on the first solution synthesis of lamivudine 5′-diphosphate in both high yield and purity. Efficient synthesis of lamivudine 5′-monophosphate was obtained through lamivudine H-phosphonate oxidation by (-)-(8,8-dichlorocamphorylsulfonyl)oxaziridine. Diphosphorylation was performed by nucleophilic substitution of the phosphorimidazolate derivative of lamivudine. HPLC coupled with UV or MS detection was found to be an invaluable tool for the follow-up of phosphorylation reactions.
2'-C-cyano-2'-deoxy-1-β-D-arabinofuranosyl-cytosine (CNDAC): A mechanism-based DNA-strand-breaking antitumor nucleoside
Matsuda,Azuma
, p. 461 - 471 (1995)
The antitumor mechanism of action of 2'-C-cyano-2'-deoxy-1-β-D- arabinofuranosyl (CNDAC) has been examined. CNDAC was designed as a potentially DNA-self-strand-breaking nucleoside. It had potent antitumor effects against various solid tumors in vitro as well as in vivo. Using a chain-extension method with Vent (exo-) DNA polymerase and a short primer/template system, we found that 5'-triphosphate of CNDAC (CNDACTP) was incorporated into the primer at a site opposite a guanine residue in the template. After further chain-extension reaction of the primer containing CNDAC at the 3'-terminus, chain elongation was not observed. Therefore, CNDACTP appeared to act as a chain-terminator. Analyses of the structure of the 3'-terminus in the primer revealed 2'-C-cyano-2',3'-didehydro-2',3'- dideoxycytidine (ddCNC) together with CNDAC and 2'-C-cyano-2'-deoxy-1-β-D- ribofuranosylcytosine (CNDC). The existence of ddCNC in the 3'-end of the primer would be due to the self-strand-break by the nucleotide incorporated next to CNDAC. We also found that CNDAC was epimerized to CNDC in near- neutral to alkaline media. Therefore, CNDC found in the primer was epimerized after incorporation of CNDACTP into the primer. We also described the metabolism of CNDAC.
Nucleosides and Nucleotides. 141. Chemical Stability of a new Antitumor Nucleoside, 2'-C-Cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine in Alkaline Medium: Formation of 2'-C-Cyano-2;-deoxy-1-β-D-ribo-pentofuranosylcytosine and Its Antitumor Activity.
Azuma, Atsushi,Hanaoka, kenji,Kurihara, Atsushi,Kobayashi, Tomowo,Miyauchi, Seiji,et al.
, p. 3391 - 3397 (1995)
We have designed 2'-C-Cyano-2'-deoxy-1-β-D-arabino-pentofuranosylcytosine (CNDAC) as a potential mechanism-based DNA-strand-breaking nucleoside, which showed potent tumor cell growth inhibitory activity against various human tumor cell lines in vitro and in vivo.When measuring the pKa of the 2'α-proton of CNDAC, we found that CNDAC epimerized to 2'-C-cyano-2'-deoxy-1-β-D-ribo-pentofuranosylcytosine (CNDC) with concomitant degradation of both CNDAC and CNDC to cytosine and 1,4-anhydro-2-C-cyano-2-deoxy-D-erythro-pent-1-enitol.Kinetic analysis of these reactions showed that abstraction of the acidic 2'-proton of CNDAC and CNDC initiated the reactions, which quickly reached an equilibrium.In the equilibrium, a concentration ratio of CNDAC and CNDC was about 3:5.Concomitant degradation of these nucleosides was found to be rather slow.Deuterium incorporation experiments with CNDAC in a D2O buffer suggested the mechanism of the β-elimination reactions is an E1cB type.These epimerization and degradation reactions were found even in neutral conditions (pH 7.5) and also occurred in RPMI 1640 cell culture medium.The discovewry of which nucleoside possesses the predominate tumor cell growth inhibitory activity was important.While both nucleosides showed potent tumor cell growth inhibitory activity against three human tumor cell lines (colon carcinoma WiDr, small cell lung carcinoma SBC-5, and stomach carcinoma MKN-74 cells) in 48 h of incubation, in 20 min of incubation, CNDAC was 11-50 times more effective than CNDC.In vivo antileukemic activity of these nucleosides against a mouse P388 model, CNDAC was obviously superior to CNDC.Therefore, tumor cell growth inhibitory activity of CNDC could be related to the quantity of CNDAC produced in the tumor cells by the equilibrium initiated by the abstraction of the acidic 2'-proton of CNDC.
Homochiral crystal generation: Via sequential dehydration and Viedma ripening
Sivakumar, Reajean,Askari, Mohammad S.,Woo, Simon,Madwar, Carolin,Ottenwaelder, Xavier,Bohle, D. Scott,Cuccia, Louis A.
, p. 4277 - 4280 (2016)
1,2-Bis(N-benzoyl-N-methylamino)benzene (2) forms centrosymmetric hydrate crystals (2·xH2O) and non-centrosymmetric anhydrous crystals. Dehydration of this hydrate (30 min at 140 °C) resulted in the formation of chiral crystals (i.e. a physical racemate of the conglomerate crystals) as verified using solid-state circular dichroism and powder X-ray diffraction. Subsequent attrition-enhanced deracemization, also known as Viedma ripening, was used to obtain homochiral crystals of 2 within 5 h.
TET-Like Oxidation in 5-Methylcytosine and Derivatives: A Computational and Experimental Study
Jonasson, Niko S. W.,Jan?en, Rachel,Menke, Annika,Zott, Fabian L.,Zipse, Hendrik,Daumann, Lena J.
, p. 3333 - 3340 (2021/09/25)
The epigenetic marker 5-methylcytosine (5mC) is an important factor in DNA modification and epigenetics. It can be modified through a three-step oxidation performed by ten-eleven-translocation (TET) enzymes and we have previously reported that the iron(IV)-oxo complex [Fe(O)(Py5Me2H)]2+ (1) can oxidize 5mC. Here, we report the reactivity of this iron(IV)-oxo complex towards a wider scope of methylated cytosine and uracil derivatives relevant for synthetic DNA applications, such as 1-methylcytosine (1mC), 5-methyl-iso-cytosine (5miC) and thymine (T/5mU). The observed kinetic parameters are corroborated by calculation of the C?H bond energies at the reactive sites which was found to be an efficient tool for reaction rate prediction of 1 towards methylated DNA bases. We identified oxidation products of methylated cytosine derivatives using HPLC-MS and GC-MS. Thereby, we shed light on the impact of the methyl group position and resulting C?H bond dissociation energies on reactivity towards TET-like oxidation.
Sources of 2,5-diaminoimidazolone lesions in DNA damage initiated by hydroxyl radical attack
Thomas, Caroline Suzanne,Pollard, Hannah Catherine,Razskazovskiy, Yuriy,Roginskaya, Marina
, p. 517 - 524 (2020/09/07)
The present study reports radiation-chemical yields of 2.5-diaminoimidazolone (Iz) derivatives in X-irradiated phosphate-buffered solutions of guanosine and double-stranded DNA. Various gassing conditions (air, N20/O2 (4:1), N2O, vacuum) were employed to elucidate the contribution of several alternative pathways leading to Iz in reactions initiated by hydroxyl radical attack on guanine. In all systems, Iz was identified as the second by abundance guanine degradation product after 8-oxoguanine, formed in 1:5 (guanosine) and 1:3.3 (DNA) ratio to the latter in air-saturated solutions. Experimental data strongly suggest that the addition of molecular oxygen to the neutral guanine radical G(-H)? plays a major in Iz production in oxygenated solutions of double-stranded DNA while in other systems it may compete with recombination of G(-H)? with superoxide and/or alkyl peroxyl radicals. The production of Iz through hydroxyl radical attack on 8-oxoguanine was also shown to take place although the chemical yield of Iz (ca 6%) in this process is too low to compete with the other pathways. The linearity of Iz accumulation with dose also indicates a negligible contribution of this channel to its yield in all systems.
Monitoring the reactivity of formamide on amorphous SiO2 by in-situ UV-Raman spectroscopy and DFT modeling
Balucani, Nadia,Bonino, Francesca,Martra, Gianmario,Pantaleone, Stefano,Signorile, Matteo,Ugliengo, Piero
, (2020/05/28)
Formamide has been recognized in the literature as a key species in the formation of the complex molecules of life, such as nucleobases. Furthermore, several studies reported the impact of mineral phases as catalysts for its decomposition/polymerization processes, increasing the conversion and also favoring the formation of specific products. Despite the progresses in the field, in situ studies on these mineral-catalyzed processes are missing. In this work, we present an in situ UV-Raman characterization of the chemical evolution of formamide over amorphous SiO2 samples, selected as a prototype of silicate minerals. The experiments were carried out after reaction of formamide at 160 ?C on amorphous SiO2 (Aerosil OX50) either pristine or pre-calcined at 450 ?C, to remove a large fraction of surface silanol groups. Our measurements, interpreted on the basis of density functional B3LYP-D3 calculations, allow to assign the spectra bands in terms of specific complex organic molecules, namely, diaminomaleonitrile (DAMN), 5-aminoimidazole (AI), and purine, showing the role of the mineral surface on the formation of relevant prebiotic molecules.
A one-pot, water compatible synthesis of pyrimidine nucleobases under plausible prebiotic conditions
Okamura, Hidenori,Becker, Sidney,Tiede, Niklas,Wiedemann, Stefan,Feldmann, Jonas,Carell, Thomas
supporting information, p. 1939 - 1942 (2019/05/02)
Herein, we report a new prebiotically plausible pathway towards a pyrimidine nucleobase in continuous manner. The route involves simultaneous methylation and carbamoylation of cyanoacetylene-derived α,β-unsaturated thioamide with N-methyl-N-nitrosourea (MNU) in aqueous media. This provides S-methylpyrimidinone in one-pot, which can be converted into a variety of 4-substituted pyrimidine nucleobases including cytosine and uracil.
Dehalogenation of Halogenated Nucleobases and Nucleosides by Organoselenium Compounds
Mondal, Santanu,Mugesh, Govindasamy
, p. 1773 - 1780 (2019/01/10)
Halogenated nucleosides, such as 5-iodo-2′-deoxyuridine and 5-iodo-2′-deoxycytidine, are incorporated into the DNA of replicating cells to facilitate DNA single-strand breaks and intra- or interstrand crosslinks upon UV irradiation. In this work, it is shown that the naphthyl-based organoselenium compounds can mediate the dehalogenation of halogenated pyrimidine-based nucleosides, such as 5-X-2′-deoxyuridine and 5-X-2′-deoxycytidine (X=Br or I). The rate of deiodination was found to be significantly higher than that of the debromination for both nucleosides. Furthermore, the deiodination of iodo-cytidines was found to be faster than that of iodo-uridines. The initial rates of the deiodinations of 5-iodocytosine and 5-iodouracil indicated that the nature of the sugar moiety influences the kinetics of the deiodination. For both the nucleobases and nucleosides, the deiodination and debromination reactions follow a halogen-bond-mediated and addition/elimination pathway, respectively.
Method for synthesizing cytosine
-
Paragraph 0034; 0036, (2018/03/26)
The invention discloses a method for synthesizing cytosine, and belongs to the field of nucleoside synthesis in organic chemistry. The method comprises the following reaction steps: reacting a raw material 3-hydroxyacrylonitrile sodium salt with ammonia to generate aminoacrylonitrile, reacting the aminoacrylonitrile with carbonate ester to obtain an intermediate, and reacting the intermediate withammonia in the presence of DBU or DBN to generate cytosine. Only a three-step reaction is carried out in the whole process, so the use of urea is avoided, and the process conditions are suitable forindustrial amplification.
