RESUMO
The nucleophilic addition-elimination reaction of 2',3',5'-tri-O-acetyl-2-fluoro-O6-[2-(4-nitrophenyl)ethyl]inosine (8) with [15N]benzylamine in the presence of triethylamine afforded the N2-benzyl[2-15N]guanosine derivative (13) in a high yield, which was further converted into the N2-benzoyl[2-15N] guanosine derivative by treatment with ruthenium trichloride and tetrabutylammonium periodate. A similar sequence of reactions of 2',3',5'-tri-O-acetyl-2-fluoro-06-[2-(methylthio)ethyl]inosine (9) and the 6-chloro-2-fluoro-9-(beta-D-ribofuranosyl)-9H-purine derivative (11), which were respectively prepared from guanosine, with potassium [15N]phthalimide afforded the N2-phthaloyl [2-15N]guanosine derivative (15; 62%) and 9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-6-chloro-2-[15N]phthalimido-9H-purine (17; 64%), respectively. Compounds 15 and 17 were then efficiently converted into 2',3',5'-tri-O-acetyl [2-15N]guanosine. The corresponding 2'-deoxy derivatives (16 and 18) were also synthesized through similar procedures.
Assuntos
Desoxiguanosina/análogos & derivados , Desoxiguanosina/síntese química , Guanosina/análogos & derivados , Guanosina/síntese química , Cromatografia , Espectroscopia de Ressonância Magnética , Isótopos de NitrogênioRESUMO
Synthetic studies on phosphodiester, phosphorothioate, and phosphorodithioate-linked oligonucleotides in terms of 2-(levulinyloxymethyl)-5-nitrobenzoyl (LMNBz) group as the base-labile protecting group for the 5'-hydroxyl groups of nucleoside 3'-H-phosphonate and -H-phosphonothioate derivatives, are described.
Assuntos
Oligonucleotídeos/síntese química , Cromatografia Líquida de Alta Pressão , Ácidos Levulínicos/química , Estrutura Molecular , Oligonucleotídeos/química , Tionucleotídeos/síntese química , Tionucleotídeos/químicaRESUMO
1) A series of synthetic works on nucleosides appropriately labeled with stable isotopes of deuterium, carbon-13, and nitrogen-15 has been undertaken, confronting the strong demands for the nucleosides in the NMR spectroscopic study deeply related to structural biology, and the synthetic methods of (2'R)- and (2'S)-2'-deoxy[2'-2H]ribonucleosides, 2'-deoxy[5'-2H]ribonucleosides, [5'-13C]ribonucleosides, 2'-deoxy[5'-13C]ribonucleosides, 2'-deoxy[4-15N]cytidine, [4-15N]cytidine, 2'-deoxy[6-15N]adenosine, and [6-15N]adenosine were developed more efficiently than ever; some oligodeoxyribonucleotides were constructed by the use of these materials and found to be extraordinarily feasible for the NMR spectroscopic studies. 2) A novel approach to oligonucleotide synthesis on CPG has been established by the use of a base-labile protecting group, i.e., 2-(levulinyloxymethyl)-5-nitrobenzoyl (LMNBz) protecting group for the 5'-hydroxyl group of nucleoside 3'-phosphoramidites.
Assuntos
Marcação por Isótopo , Nucleosídeos/síntese química , Espectroscopia de Ressonância Magnética , Conformação de Ácido Nucleico , Oligonucleotídeos/síntese químicaRESUMO
Nucleophilic substitution reaction of 6-chloro-2-fluoro-9-beta-D-ribofuranosyl-9H-purine derivative, prepared from guanosine, with potassium [15N]phthalimide at 40 degrees C for 9 h in DMF, followed by hydrolysis, afforded [2-(15)N]guanosine derivative efficiently. The corresponding 2'-deoxy derivative was also synthesized through a similar procedure.
Assuntos
Desoxiguanosina/análogos & derivados , Desoxiguanosina/síntese química , Guanosina/análogos & derivados , Guanosina/síntese química , Indicadores e Reagentes , Marcação por Isótopo/métodos , Estrutura Molecular , Isótopos de NitrogênioRESUMO
A comparative study on the utility of 2-(levulinyloxymethyl)-5-nitrobenzoyl (LMNBz) and 2-(levulinyloxymethyl)benzoyl (LMBz) protecting groups for the 5'-positions of nucleoside 3'-phosphoramidite derivatives in the oligonucleotide synthesis is presented in terms of the syntheses of TpTpT, TpTpTpT, and UpCpApGpUpUpGpG. In addition we describe the synthesis, using the LMNBz protecting group, of the CpCpA terminus triplet of tRNAs bearing exocyclic amino groups with 15N-labeling, and the trimer Gp[A*]pG containing 2'-O-(beta-D-ribofuranosyl)adenosine ([A*]), the latter of which is found at position 64 in the yeast initiator tRNA(Met).
Assuntos
Nucleotídeos , Oligonucleotídeos/síntese química , Tionucleotídeos/química , Cromatografia Líquida de Alta Pressão , Modelos Químicos , Oligonucleotídeos/química , RNA de Transferência/químicaRESUMO
Synthetic studies on the CpCpA terminus triplet, whose exocyclic amino groups are all labeled with 15N, and a phosphorodithioate-linked oligonucleotide in terms of 2-(levulinyloxymethyl)-5-nitrobenzoyl (LMNBz) group as the novel base-labile protecting group for the 5'-hydroxyl groups of nucleoside 3'-phosphoramidites, are described.
Assuntos
Oligodesoxirribonucleotídeos/síntese química , Oligorribonucleotídeos/síntese química , Tionucleotídeos , Indicadores e Reagentes , Estrutura Molecular , Oligodesoxirribonucleotídeos/química , Oligorribonucleotídeos/química , Compostos OrganofosforadosRESUMO
For further improvement in the investigation to utilize a cellulose acetate derivative as a novel type of polymer-support for the synthesis of oligonucleotides, the investigations on utilizing another spacer; on protecting groups for O6-position of guanosine unit, ribothymidine, and pseudouridine; and on a novel protecting group for the introduction of phosphate function at 5'-terminal position, targeting the syntheses of 13-mer, ApApGpGpApApApApUpUpApUpG, 11-mer, pCpUpCpGpUpCpCpApCpCpA, and 12-mer, UpCpCpGpGprTp- psipCpGpApUpU, found in the partial structures of a yeast tRNA(Ala), will be described in detail.
Assuntos
Oligorribonucleotídeos/síntese química , Sequência de Bases , Celulose/análogos & derivados , Indicadores e Reagentes , Dados de Sequência Molecular , Pseudouridina , RNA de Transferência de Alanina/síntese química , Saccharomyces cerevisiaeRESUMO
The title linker was synthesized in the manner of dimer-units introduction through liquid-phase and phosphoroamidate approaches involving deamidation with tetrabutylammonium nitrite-acetic anhydride.
Assuntos
Oligodesoxirribonucleotídeos/síntese química , Anidridos Acéticos , Amidas , Ácidos Fosfóricos , Compostos de Amônio QuaternárioRESUMO
4-(2-Hydroxyethylsulfonyl)dihydrocinnamate derivative of cellulose acetate (D.S. 1.77) was used for polymer support synthesis of oligonucleotides bearing a phosphodiester function at the 3'-terminal position, taking into consideration that the cellulose derivative is readily soluble in pyridine, but slightly soluble in a solvent such as ethanol.
Assuntos
Oligonucleotídeos/síntese química , Celulose/análogos & derivados , Indicadores e Reagentes , SolubilidadeRESUMO
Acylation of ribonucleosides through acyl chlorides in pyridine was induced with high regioselectivity under a controlled condition to give the corresponding 2',5'-diacylates in excellent yields and 2'-acylates, depending on the amount of the acyl chlorides used. On the other hand, a treatment of these resulting acylates on a silica gel (Wakogel C-300, Wako Pure Chemical Co. Ltd.) conducted their transformation into the corresponding 3',5'-diacylates or 3'-acylates effectively. These resulting 2',5'- and 3',5'-diacylates were further derived, by the known method, into the 3'- and 2'-O-tetrahydropyran-2-yl ribonucleoside derivatives, respectively, with which some ribonucleotide oligomer syntheses have been performed.
Assuntos
Oligorribonucleotídeos/síntese química , Piranos/síntese química , Ribonucleosídeos/síntese química , Acilação , Indicadores e Reagentes , Relação Estrutura-AtividadeRESUMO
Partial phenylcarbamoylation of ribonucleosides by metal carboxylates - phenyl isocyanate system was found to be induced at 2'-position with high regioselectivity in good yields, similar to that by amines - phenyl isocyanate system; these results prompted us to perform synthesis of oligoribonucleotides bearing 2'-5' phosphodiester linkage starting either from 5'-0-acetyl-2'-0-phenylcarbamoyl or from 2', 5'-bis(phenylcarbamo)yl derivatives through the sequence of reactions, i.e. tetrahydropyranylation at 3'-position, decarbamoylation and deacylation with sodium methoxide in methanol both at 2'- and 5'-positions, dimethoxytritylation at 5'-position, and phosphorylation at 2'-position with 5-chloro-8-quinolylphosphate/8-quinolinesulfonyl chloride, followed by the usual coupling procedures by Takaku et al).