Uracil Fragment Research Articles

Synthesis of acyclic and macrocyclic analogs of Di-, Tri-, and tetranucleotides

Compounds consisting of two or three uracil fragments were synthesized by reaction of methyl-substituted uracil sodium salts with 1-(6-bromohexyl)-3,6-dimethyluracil or 1,6-dibromohexane. Treatment of these compounds with paraformaldehyde gave the corresponding pyrimidinophanes and acyclic compounds in which the uracil fragments are linked through methylene bridges. Uracil derivatives having no substituent on N3 were synthesized by reactions of silylated uracils with 1,3-bis(6-bromohexyl)uracil or 4,4′-(6-bromohexyloxy)diphenylmethane. The acyclic compound was converted into pyrimidinophane containing uracil fragments with N3H groups. A trinucleotide analog including uracil and two adenine fragments was synthesized from 1,3-bis(6-bromohexyl)uracil.

Ionizing fragmentation of uracil and 5-bromouracil by electron impact in gas phase and hyperthermal Ar + ion irradiation in condensed phase

The chemical composition and formation channels of charged fragments of uracil (U) and 5-bromouracil (BrU) produced by 70 eV electron impact in gas phase and 10–200 eV Ar + ion irradiation in condensed phase are investigated in parallel with that of thymine (T). This is part of our effort to unravel possible different molecular level mechanisms of DNA damage caused by heavy ion radiation and the radiosensitivity of 5-BrU observed during UV, X- and γ-ray radiation. Abundant ionic fragments are produced from the three molecules by both electron impact and ion irradiation through similar bond-breaking channels due mainly to their very similar molecular structures. During electron impact major cation fragments are identified as [M − OCNH] +, NHCHCCH 3 +(T)/NHCHCH +(U)/NHCHCBr +(BrU), OCNH 2 +, HNCH +/CO +, C x H y + ( x = 1–3; y = 0–4), etc. and a parent cation [M] + as well where M = T, U or 5-BrU. During ion irradiation some of these fragments partially or completely appear in their protonated forms, and an additional cation fragment [M − O] + is also observed. Major anion fragments produced by ion irradiation are H −, O −, CN −, OCN − for all three molecules with trace amount of hydrocarbon anions. An additional Br − anion is produced for 5-BrU. The parent anions are discernable in their deprotonated forms only from very thin films. During Ar + ion irradiation, fragment desorption begins at incident ion energies down to 20 eV. Anion fragment desorption appears at much higher energies at around 40 eV, and strongly depends on the film thickness.

Synthesis and structures of pyrimidinophanes containing a nitrogen atom in the bridge

The reactions of 1,3-bis(5-bromopentyl)-5-methyl-or 1,3-bis(5-bromopentyl)-6-methyl-uracil with benzylamine afforded pyrimidinophanes containing the nitrogen atom in the polymethylene bridge. Single-crystal X-ray diffraction study and NMR and UV spectroscopic study in solution demonstrated that the phenyl and uracil fragments in the macrocycles are in spatial proximity. Unlike the known macrocycles containing the pyrimidine ring, the pyrimidinophanes under study are conformationally rigid.

Study of the Factors that Control the Ratio of the Products between 5-Fluorouracil, Uracil, and Tetrahydrobenzoxazepine O,O-Acetals Bearing Electron-Withdrawing Groups on the Nitrogen Atom

(RS)-1-(2-Nitrobenzenesulfonyl)- and (RS)-1-(4-nitrobenzenesulfonyl)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepines are better substrates than 1-acyl-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine derivatives for the Lewis acid mediated condensation reaction with pyrimidine bases to give O,N-acetals. Acetonitrile, stannic chloride, 50 degrees C, and a reaction time higher than 48 h are the optimum conditions for such condensation reactions. Under these conditions, 5-fluorouracil preferably links to the aminalic carbon through its N-1" position, while the attachment of the uracil fragment is through N-3" or N-1" of the cyclic or acyclic products, respectively. The causes that influence the course of the reactions are analyzed and discussed. Examination of the (1)H NMR spectra revealed the presence of a single form for the secondary amine 11 and of two conformers for the tertiary sulfonamides 7a,b, 9a,b, and 10b and for the amides 7d and 13, with the following distribution: 7a, 59/41; 7b, 53/47; 9a, 52/48; 9b, 59/41; 10b, 56/44; 7d, 50/50; 13, 80/20. On increasing the temperature, the (1)H NMR spectrum (DMSO-d(6)) of 7b showed coalescence at 110 degrees C. The torsional barrier determined [DeltaG(c)++ value of 19.0 +/- 0.2 kcal.mol(-1) (79.1 +/- 1.0 kJ.mol(-1))] proved to be the highest ever observed for sulfonamide moieties.

Electron attachment to uracil: effective destruction at subexcitation energies.

We demonstrate that electrons at energies below the threshold for electronic excitation (<3 eV) effectively decompose gas phase uracil generating a mobile hydrogen radical and the corresponding closed shell uracil fragment anion (U-H)(-). The reaction is energetically driven by the large electron affinity of the (U-H) radical. This observation has significant consequences for the molecular picture of radiation damage, i.e., genotoxic effects or damage of living cells due to the secondary component of high energy radiation.

Cq+-induced excitation and fragmentation of uracil: effects of the projectileelectronic structure

Ionization and fragmentation of the RNA base uracil (C4H4N2O2) by means of Cq+ ions(q = 1–6)has been studied for ion kinetic energies ranging from 2 to 120 keV. Whereas for Cq+(q = 1, 3, 4,5, 6) very similar fragmentation yields are observed which increase with the projectilevelocity v,C2+ ions not only induce a fundamentally different fragmentationpattern but also lead to a decrease of fragmentation with ion velocityv. Atlow velocities, even almost complete fragmentation is observed. Our findings canbe explained by differences in the electronic structures of the Cq+ ions as well as byemploying the electronic stopping model previously applied to ion–fullereneinteractions.

Mannich Reaction as a Convenient Route to New Macrocyclic Compounds Containing an Uracil Fragment

Mannich reaction of 1,3-bis[4-(2-mercaptomethylphenoxy)butyl]-6-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione, formaldehyde, and N-benzylamine afforded a 24-membered macrocyclic compound containing an uracil fragment, 1,3-(11-benzyl-6,7:15,16-dibenzo-5,17-dioxa-9,13-dithia-11-aza-6,15-heneicosadiene-1,21-diyl)-6-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione.

Oxidative addition of unsaturated acid esters to 1,3-dimethyluracil and pyrimidine nucleosides

When alkyl esters of acrylic and sorbic acids or acrolein diethylacetal are reacted with 1,3-dimethyluracil or 1-β-D-xylofuranosyluracil in the presence of Pd(OAc)2, oxidative addition takes place at position 5 of the uracil fragment.

Synthesis and biological activity of 1,3-di(3-dimethoxyphosphorylpropyl) derivatives of uracil and 6-methyluracil

The uracil fragment is frequently encountered in nature as part of heterocyclic compounds. It is included in DNA and RNA in the form of nucleotides. Many uracil derivatives exhibit a high level of biological activity. The alkylated and acylated derivatives of 5-fluorouracil, for example, l-(2-tetrahydrofuryl)-5-fluorouracil [2], is widely used for the chemotherapy of malignant tumors. Derivatives of pyrimidine nucleosides and nucleotides are used as antiviral preparations [ii].

ChemInform Abstract: X‐Ray Structural Studies on Metal Complexes of Uracil and Orotic Acid. A Survey of Coordination‐Induced Changes in the Uracil Fragment

ChemInform Abstract: X‐Ray Structural Studies on Metal Complexes of Uracil and Orotic Acid. A Survey of Coordination‐Induced Changes in the Uracil Fragment

Influence of uracil photohydrate formation on the conformational properties of heterodinucleoside monophosphates

AbstractThe structural properties of uracil photohydrates at the monomer and dimer level in aqueous solution have been examined in detail by nmr spectroscopy. Based on such evidence, the absolute configurations of the two possible diastereomers have been assigned, and the conformational perturbations induced by photohydration have been evaluated. In all instances, photohydration shifts the 2E ⇌ 3E puckering equilibrium of the sugar ring of the uridylyl fragment towards 2E (from 12–18%). In addition, for both dimers examined in detail, ho6UpA and Apho6hU, the effect of dimerization on sugar pucker is such that the 3′‐terminal unit shows a clear increase in the percentage of 3E (relative to the appropriate 5′‐mononucleotide), whereas the percentage 3E of the 5′‐terminal unit shows no change. This is contrary to the findings in the normal dinucleoside monophosphates, where an increased preference for 3E pucker occurs in both residues on dimerization and increased base stacking. Significant base–base interactions were observed in both hydrated dimers despite the loss of the planar π‐system in the uracil fragment. In addition, the rate of photohydration for a particular dimer pair (e.g., ApU and UpA or GpU and UpG) is shown to be inversely dependent on the amount of base stacking in the parent dimer. This latter parameter has also been correlated with the ratio of the two possible diastereomers formed in the reaction and is associated with a preferential attack at one face of the pyrimidine base ring. The shift of the sugar puckering equilibrium towards 2E has been compared with similar shifts observed when adenosine and guanosine are methylated at N(1) and N(7), respectively. The possible biological significance of the above‐mentioned conformational aspects is discussed.

Investigations in the xanthine series and among its condensed derivatives

A method has been developed for obtaining derivatives of 8-methyl-2,3-dihydro-6H-imidazo[1,2-f]xanthine. It has been established that 2,3-dihydroimidazo[1,2-f]-xanthines alkylate in position 6 of the uracil fragment. A method has been developed for obtaining derivatives of 2,3-dihydroimidazo[1,2-f]purin-7-one. The structure of the compounds synthesized have been confirmed by IR and PMR spectroscopy.