- 1-Ethyluracil, a New Scaffold for Preparing Multicomponent Forms: Synthesis, Characterization, and Computational Studies
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In this work, we describe the successful preparation of a series of cocrystals of the modified nucleobase 1-ethyluracil with different coformers in a 1:1 or 2:1 (nucleobase:coformer) ratio including urea (URE) or some compounds containing carboxylic and hydroxyl groups such as l-malic acid (MAL), l-tartaric acid (TAR), 2-hydroxybenzoic acid (SAL), 4-hydroxybenzoic acid (4HB), and 2,4-dihydroxybenzoic acid (DHB). The influence of the hydroxyl substituent on the alkyl chain for 1·TAR and 1·SAL cocrystals or the phenyl ring for 1·SAL, 1·4HB, and 1·DHB multicomponent solids was studied. All of the compounds were characterized by powder X-ray diffraction, FT-IR, and thermal methods. Moreover, for those whose single-crystal structures could be determined, computational studies were also performed to investigate the factors that may affect the cocrystal formation, the recurrent motifs, and the energies associated with the H-bonding interactions using DFT calculations and a combination of the quantum theory of atoms in molecules (QTAIM) and the noncovalent interaction index (NCIplot) computational tools.
- Roselló, Yannick,Benito, Mónica,Barceló-Oliver, Miquel,Frontera, Antonio,Molins, Elies
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p. 4857 - 4870
(2021/08/23)
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- Triphenylphosphine-free approach for one-pot N-alkylation of purine, pyrimidine, and azole derivatives with alcohols using P2O5/KI: A facile and selective route to access carboacyclic nucleosides
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A facile, selective, and mild synthetic approach for one-pot N-alkylation of nucleobases and other related N-heterocycles via alcohols, using a mixture of P2O5 and KI is described. The reaction of structurally diverse purines, pyrimidines, and/or azoles with primary alcohols with the use of P2O5/KI and basic mixture of Et3N/K2CO3 in refluxing DMF affords the corresponding N-alkyl derivatives (carboacyclic nucleosides) in good to reasonable yields. The influence of different parameters comprising solvent, base, temperature, and substrate/reagent ratios was assessed on the reaction progress. The secondary and tertiary alcohols were failed to react with nucleobases. The main advantageous of current protocol is formation of water soluble side products in which provides simple work-up and purification processes.
- Behrouz, Somayeh,Soltani Rad, Mohammad Navid,Ahmadi, Samira
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supporting information
(2019/08/12)
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- Copper-Catalyzed Regioselective Direct C–H Thiolation and Thiocyanation of Uracils
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A novel copper-catalyzed direct C–H thiolation and thiocyanation of uracils using disulfides and thiocyanate salts respectively as coupling partners are described. These reactions enable the C–H bond cleavage and C–S bond formation to proceed efficiently under relatively mild conditions, providing useful methods for a preparation of a series of thio-substituted at the C5 position of uracil derivatives. These protocols exhibit several merits including simple experimental procedures, readily accessible substrates and reagents, broad scopes, high yields, and excellent regioselectivity. Preliminary mechanistic studies revealed that a radical pathway is likely to be involved.
- Noikham, Medena,Yotphan, Sirilata
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supporting information
p. 2759 - 2766
(2019/04/08)
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- A diversity of alkylation/acylation products of uracil and its derivatives: Synthesis and a structural study
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tert-Butyl dicarbonate (Boc2O) and ethyl iodide (EtI) reactions with uracil (U), thymine (T) and 6-methyluracil (6-MU) were performed following routine procedures in pyridine/DMF solvents and with DMAP as the catalyst. Among 20 synthesized compounds, a derivative of 6-methyluracil substituted by the Boc-pyridine moiety at the C5 position appeared unexpectedly. The NMR spectra confirmed the molecular structure of all uracil derivatives. Parallel quantum mechanical DFT calculations supported the experimental findings.
- Michalak, Olga,Cmoch, Piotr,Krzeczyński, Piotr,Cybulski, Marcin,Le?, Andrzej
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p. 354 - 362
(2019/01/10)
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- Straightforward pyrimidine ring construction: A versatile tool for the synthesis of nucleobase and nucleoside analogues
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A general route to 1,2,4-trisubstituted pyrimidines is described in one to three steps from a common key precursor, diazadienium iodide 2. An efficient preliminary [4+2] cyclocondensation reaction between the azabutadiene building block 2 and various iso(thio)cyanates constitutes an original construction of the pyrimidine skeleton. Subsequent structural modifications on the heterocycle allow the elaboration of a 1-substituted pyrimidine library that includes nucleoside analogues. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Robin, Aelig,Julienne, Karine,Meslin, Jean-Claude,Deniaud, David
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p. 634 - 643
(2007/10/03)
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- HSAB-driven chemoselective N1-alkylation of pyrimidine bases and their 4-methoxy- or 4-acetylamino-derivatives
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The lithium salts of the conjugated bases of 4-methoxy- and 4-acetylamino-2(1H)-pyrimidinones 1-3 undergo highly chemoselective N1-methylation or ethylation when treated with methyl- or ethylsulfate (hard electrophiles) in dry dioxane, while the use of DMF as solvent results in competitive O2-alkylation. Potassium salts of the same bases in DMF undergo prevalent O2-attack. Under the same conditions, a similar but less chemoselective behaviour is observed in alkylation of thymine and uracil, where some N3-attack occurs. This can be rationalised in terms of the HSAB principle.
- Gambacorta, Augusto,Tofani, Daniela,Loreto, Maria Antonietta,Gasperi, Tecla,Bernini, Roberta
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p. 6848 - 6854
(2007/10/03)
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- Ring opening photoreactions of cytosine and uracil with ethylamine
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The photochemical reactions of cytosine (Cyt) and uracil (Ura) with ethylamine, an analog of the side chain of the amino acid lysine, have been studied. After irradiation of Cyt in aqueous ethylamine at λ = 254 nm, N-(N′-ethylcarbamoyl)-3-aminoacrylamidine (Ia) and N-(N′-ethylcarbamoyl)-3-ethylaminoacrylamidine (Ib) were isolated as products, while irradiation of Ura gave N-(N′-ethylcarbamoyl)-3-aminoacrylamide (IIa) and N-(N′-ethylcarbamoyl)-3-ethylaminoacrylamide (IIb) as products. Studies in which Ia and IIa were incubated with ethylamine at various pH values indicate that Ib and IIb are secondary products produced via thermal reactions of Ia and IIa with ethylamine. Heating of Ia and Ib leads to ring closure with the resultant formation of 1-ethylcytosine; small amounts of 1-ethyluracil are also produced. Heating of IIa and IIb produces 1-ethyluracil as the sole product. Spectroscopic properties were determined for each of these opened ring products, as well as for N-(N′-ethylcarbamoyl)-3-amino-2-methylacrylamidine (III) and N- (N′-ethylcarbamoyl)-3-amino-2-methylacrylamide (IV). Quantum yield measurements showed that Ia was formed with a Φ of 1.6 × 10-4 at pH 9.8, while Φ for formation of IIa was 7.2 × 10-4 at pH 11.5. A profile of the relative quantum yield for formation of Ia, determined as a function of pH, showed that the maximum quantum yield occurs at around pH 9.5; the analogous profile for IIa shows a maximum quantum yield at pH 11.3 and above. Acetone sensitization does not produce Ia in the Cyt-ethylamine system, which indicates that the known triplet state of Cyt is not involved in reactions leading to this opened ring product.
- Hom, Kellie,Strahan, Gary,Shetlar, Martin D.
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p. 243 - 253
(2007/10/03)
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- The photocycloaddition reactions of uridine and related compounds with 2,3-dimethyl-2-butene
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The photochemical reactions of uracil and 5-fluorouracil derivatives with simple alkenes have been investigated. Photocycloaddition of uracil or 5-fluorouracil derivatives and 2,3-dimethyl-2-butene in acetone gave an enantiomeric mixture of cross cycloadducts (4, 7) in moderate yields. Under similar conditions, diastereomers of 4-substituted 7,7,8,8-tetramethyl-cis-2,4-diazabicyclo[4.2.0]octane-3,5-dione nucleosides (14-17) were formed from uridine or 5-fluorouridine derivatives in good yields. The structures and stereochemistry of these cycloadducts of the nucleoside series were elucidated on the basis of the proton nuclear magnetic resonance spectra and X-ray crystallographic analysis.
- Ishikawa,Itoh,Takayanagi,Oshima,Kawahara,Mizuno,Ogura
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p. 1922 - 1930
(2007/10/02)
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- USE OF 5-DEOXY-ribo-HEXOFURANOSE DERIVATIVES FOR THE PREPARATION OF 5'-NUCLEOTIDE PHOSPHONATES AND HOMORIBONUCLEOSIDES
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A convenient and general method is proposed for the synthesis of 5'-nucleotide phosphonate analogs starting from 5-deoxy-1,2-O-isopropylidene-α-D-xylo-hexofuranose which can easily be produced in preparative quantities from D-glucose.Phosphonate IIIa was synthesized by means of the Arbuzov reaction between 3-O-benzoyl-6-bromo-5,6-dideoxy-1,2-O-isopropylidene-α-D-ribo-hexofuranose and triethyl phosphite.The consecutive acetolysis, condensation with uracil and N6-benzoyladenine bis-trimethylsilyl derivatives and deblocking possessed phosphonate analogs of 5'-nucleotides in good yields.The intermediate 5-deoxy-1,2-O-isopropylidene-α-D-ribo-hexofuranose derivatives were used for the preparation of homonucleosides.
- Mikhailov, Sergei N.,Padyukova, Nelly Sh.,Karpeiskii, Marat Ya.,Kolobushkina, Lidiya I.,Beigelman, Leon N.
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p. 1055 - 1066
(2007/10/02)
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- A NEW SCHEME FOR THE SYNTHESIS OF 5'-NUCLEOTIDE PHOSPHONATE ANALOGS
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A convenient and general method is proposed for the synthesis of 5'-nucleotide phosphonate analogs starting from 5-deoxy-1,2-O-isopropylidene-α-D-xylo-hexofuranose (1).
- Padyukova, Nelly Sh.,Karpeisky, Marat Ya.,Kolobushkina, Lidiya I.,Mikhailov, Sergey N.
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p. 3623 - 3626
(2007/10/02)
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- Improved One-Step Procedure for the Preparation of 1-Substituted and 1,3-Disubstituted Uracils and 2-Thiouracils
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A convenient one-pot procedure for the synthesis of 1-substituted and 1,3-disubstituted uracils and 2-thiouracils consists of acylation of ureas or thioureas with methyl 3,3-dimethoxypropanoate in the presence of a strong base, and acidic work-up.The yields range from 36 to 99percent.In all cases, only one regioisomer is isolated.
- Winckelmann, Ib,Larsen, Erik H.
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p. 1041 - 1044
(2007/10/02)
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- Cephalosporins
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Cephalosporins represented by the formula X-S-Y wherein X is a deacetoxycephalosporinyl group and Y is a 6-membered heterocyclic group containing 1-3 nitrogens at least one of which is substituted and at least one of which is adjacent to a carbonyl group, said heterocyclic group containing one or more ring substituents and being characterized by being non-aromatic and not enolizable to an aromatic form.
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