- Practical and Reliable Synthesis of 1,2-Dideoxy-D-ribofuranose and its Application in RNAi Studies
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We developed a practical and reliable method for synthesizing an abasic deoxyribonucleoside, 1,2-dideoxy-D-ribofuranose (dRH) via elimination of nucleobase from thymidine. To synthesize oligonucleotides bearing dRH by the standard ph
- Nagaya, Yuki,Kitamura, Yoshiaki,Nakashima, Remi,Shibata, Aya,Ikeda, Masato,Kitade, Yukio
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- Transfer hydrogenation as a redox process in nucleotides
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Using a combined theoretical and experimental strategy, the heats of hydrogenation of the nucleotide bases uracil, thymine, cytosine, adenine, and guanine have been determined. The most easily hydrogenated base is uracil, followed by thymine and cytosine. Comparison of these hydrogenation enthalpies with those of ketones and aldehydes derived from sugar models indicates the possibility of near-thermoneutral hydrogen transfer between uracil and the sugar phosphate backbone in oligonucleotides. (Figure Presented)
- Achrainer, Florian,Emel'yanenko, Vladimir N.,Tantawy, Waled,Verevkin, Sergey P.,Zipse, Hendrik
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p. 10426 - 10429
(2015/04/14)
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- An expedient biocatalytic procedure for abasic site precursors useful in oligonucleotide synthesis
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Preparation of abasic site precursors through a divergent chemoenzymatic synthesis has been accomplished. Several biocatalysts and acylating agents were studied furnishing a practical and scalable green method useful for industrial applications. Highly re
- Martinez-Montero, Saul,Fernandez, Susana,Sanghvi, Yogesh S.,Gotor, Vicente,Ferrero, Miguel
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experimental part
p. 5960 - 5966
(2011/10/05)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS
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Disclosed herein are cannabinoid receptor ligands of formula (I) wherein A1, A5, Rx, X4, and z are as defined in the specification. Compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and compositions are also disclosed.
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Page/Page column 32
(2010/04/23)
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- COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS
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Disclosed herein are compounds of formula (I) wherein Ring A and R1 are as defined in the specification. Pharmaceutical compositions comprising such compounds, and methods for treating conditions and disorders using such compounds and pharmaceutical compositions are also disclosed.
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Page/Page column 39
(2010/10/19)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS
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The present invention relates compounds of formula (I) wherein A and R1 are as defined in the specification, pharmaceutical compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and pharmaceutical compositions.
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Page/Page column 36
(2009/05/29)
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- Glycosidic Bond Cleavage of Thymidine by Low-Energy Electrons
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Thymidine was exposed to low-energy electrons (LEE) as a thin solid film under a high vacuum. Nonvolatile radiation products, remaining on the irradiated surface, were analyzed by HPLC/UV and GC/MS. Here, we show that exposure of thymidine to 3-100 eV electrons gives thymine as a major product with a yield of 3.2 × 10-2 per electron (about one-third of the total decomposition of thymidine). The formation of thymine indicates that LEE induces cleavage of the glycosidic bond separating the base and sugar moieties, suggesting a nonionizing resonant process involving dissociative attachment (a new mechanism of DNA damage involving the interaction of LEE. Copyright
- Zheng, Yi,Cloutier, Pierre,Hunting, Darel J.,Wagner, J. Richard,Sanche, Leon
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p. 1002 - 1003
(2007/10/03)
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- Biomimetic cyclisation of prebrevetoxin polyepoxide models
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(E)-1,3-Dihydroxyhex-4-ene and (E)-1,3-dihydroxy-4-methylhex-4-ene undergo epoxidation with peracetic acid and in situ cyclisation to give a mixture of tetrahydro-furans and -pyrans, whereas comparable compounds lacking the allylic hydroxyl group give pre
- Kelly, David R.,Nally, James
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p. 3251 - 3254
(2007/10/03)
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- Synthesis of bis-abasic cyclic dinucleotide, bis-(3→5)-cyclic bis(1,4-anhydro-2-deoxy-D-erythro-pentitol-3-phosphate), an inhibitor of HIV-1 integrase
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Bis-abasic cyclic dinucleotide, bis-(3→5)-cyclic bis(1,4-anhydro-2-deoxy-D-erythro-pentitol-3-phosphate) (1), was prepared from 2-deoxy-D-ribose in nine convergent steps, in 18% overall yield.
- Chenault, H. Keith,Mandes, Robert F.
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p. 11033 - 11038
(2007/10/03)
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- 2-thiosubstituted carbapenems
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Carbapenem antibiotic compounds of the general formula: STR1 wherein the moiety STR2 is a 4, 5 or 6 membered mono, di- or tri- substituted oxygen or sulfur containing ring; wherein Z is oxygen, sulfur, sulfoxide and sulfone, pharmaceutical compositions thereof useful for the treatment of bacterial infections, processes for preparing the compounds and new intermediates useful in the process.
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- How do the gauche and anomeric effects drive the pseudorotational equilibrium of the pentofuranose moiety of nucleosides?
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The conformational characteristics of abasic 1-deoxy sugars 1, 2, and 3 and pentofuranose moieties in 2′,3′-dideoxy-[ddA (6), ddG (7), ddC (8)], 2′-deoxy-[dA (9), dG (10), dC (11)], and ribo-β-D-nucleosides [Ade (12), Gua (13), Cyt (14)] were established through the analysis of vicinal proton-proton coupling constants extracted from their 500-MHz 1H-NMR spectra recorded at 20 K intervals in the temperature range from 278 to 358 K in D2O solution. Two novel deuterated analogues of (S)-tetrahydrofurfuryl alcohol (1), 2-(S)-(hydroxymethyl)-4-(R)-deuteriotetrahydrofuran (4) and 2-(S)-(hydroxymethyl)-3-(S)-deuteriotetrahydrofuran (5), have enabled unequivocal assignment of the complex nine-spin system in its 1H-NMR spectrum. The van't Hoff plots of (ln(XS/XN)] as a function of 1/T gave ΔH° and ΔS° values of pseudorotational equilibrium in pentofuranoses 1-3 and pentofuranose moieties in nucleosides 6-14. The values of ΔH° were dissected into various stereoelectronic effects (gauche versus anomeric effects) of exocyclic substituents on the pentofuranose moiety. Clearly, the gauche effect of the O4′-C4′-C3′-O3′ fragment drives the pseudorotational equilibrium to the S-type conformations, while the gauche effect of the O4′-C1′-C2′-O2′ fragment pushes the pseudorotational equilibrium to the N. These gauche effects are the strongest factors responsible for driving the N ? S pseudorotational equilibrium. The strength of the gauche effect of the O4′-C4′-C3′-O3′ fragment in abasic sugars 1-3 is further tuned by the presence of a heterocyclic base at C1′ in nucleosides 6-14. The relatively weaker anomeric effect of the heterocyclic base drives the N ? S equilibrium to the N. The assessment of the relative strengths of the anomeric effects in 2′,3′-dideoxy, 2′-deoxy-, and ribo-β-D-nucleosides has shown that the anomeric effect of the cytosine base is stronger than the anomeric effect of the adenine or guanine base. The experimental data suggest that the anomeric effect is considerably reduced as O4′ experiences the electron-withdrawing effect(s) of 2′(3′)-hydroxyls. The differences in the conformational preferences found in purine and pyrimidine ribonucleosides were additionally attributed to the distinct relative strength of the gauche effect of the N-C1′-C2′-O2′ fragment. The preference for the gauche orientation of the N-C1′-C2′-O2′ fragment and therefore S-type sugar conformation is affected by the nature of the purine or pyrimidine glycosyl nitrogen atom.
- Plavec, Janez,Tong, Weimin,Chattopadhyaya, Jyoti
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p. 9734 - 9746
(2007/10/02)
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- Oligophosphates with an antiviral action
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Novel oligophosphates with an antiviral action of the formula STR1 in which n is 3-50, B and E are, independently of one another, O, S or NH, A is O, NR or S, D is O, S or NR2, in which independently each R is H, alkyl, aralkyl or aryl, and
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- SYNTHESIS AND CONFORMATIONAL STUDIES OF A NUMBER OF SATURATED BICYCLIC SIX-MEMBERED RING PHOSPHITES
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An 1H NMR study of the conformation of the dioxaphosphorinane ring of a number of diastereoisomeric bicyclic saturated six-membered ring phosphites (3ab-10ab) has been performed.The dioxaphosphorinane ring of these phosphites is transannelated with a tetrahydrofuran, cyclopentane, tetrahydropyran or cyclohexane ring.The substituent on the phosphorus atom is a methoxy or phenoxy group.It is shown that the cis isomers 3a-10a prefer a chair conformation of the dioxaphoshorinane ring, independent of the substituent on the phosphorus atom and of the nature of the transannelated ring.In contrast, for the trans isomers 3b-10b a twist rather than a chair conformation of the dioxaphosphorinane ring is preferred.The fraction of the twist conformer in the trans isomers is mainly determined by the substituent on phosphorus.The size and composition of the transannelated ring are relatively unimportant in this respect.For both cis and trans isomers, the preferred geometry is solvent-independent.The measured 3JPOCH couplings of the cis isomers 3a-10a are used to formulate an expression for the dependence of such couplings upon dihedral angles in bicyclic phosphites.
- Hermans, Rob J. M.,Buck, Henk M.
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p. 255 - 266
(2007/10/02)
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- P(V) trigonal bipyramidal phosphoranes as model compounds for the description of cAMP-catalyzed reactions
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13C NMR low-temperature investigations have revealed that the dioxaphospharinane ring, trans-annelated with a cyclopentane ring (3), prefers an equatorial-apical alignment in trigonal bipyramidal phosphoranes.However, the 13C NMR low-temperature investigations of the model compound, in which the dioxaphospharinane ring is trans-annelated with a tetrahydrofuran ring (4), have shown that the ligand exchange (pseudorotation) in this compound is very fast on the NMR time scale, even at low temperature.These results are in fairly good agreement with quantum-chemical calculations.
- Ool, Peter J. J. M. van,Buck, Henk M.
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p. 119 - 122
(2007/10/02)
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