Carboxyamidation of Purine Nucleosides: New Secondary 8-Carboxamidopurine Nucleosides

Abstract

Palladium catalyzed carboxyamidation at the 8-position of 8-bromoadenosine and 8-bromoguanosine nucleosides is a versatile reaction, which allows primary, secondary, heterocyclic, aromatic mine and amino acids to be incorporated into purine nucleosides.     

8-Diazoguanosine, 2,8-Diaminoadenosine and Other Purine Nucleosides Derived from Guanosine

Abstract

Diazotization of 8-aminoguanosine gave 8-diazoguanosine (2) which is stable in neutral and basic media, but decomposes to D-ribose and 8-diazoguanine in acidic conditions. 2-Amino-6,8-dichloro-9-(2,3,5-tri-0-acetyl-β-D-ribo-furanosyl)purine (5) was employed to synthesize 9-β-D-ribofuranosyl-2,6,8-triaminopurine (8) and a number of N6-alkyl-2-amino-8-chloro-9-β-D-ribofuranosylpurines.     

Fluorine Substituted Analogs of Nucleosides and Nucleotides

Abstract

The synthesis and ¹⁹F NMR spectra of dTMP and TpT analogues in which the phosphate group is replaced by a difluoromethylphosphonate group are described.     

Electrochemical Oxidations of Some Purine Nucleosides. Formation of Some Novel Purine Oligonucleosides

Abstract

The electrochemical oxidation of the purine nucleosides xanthosine and guanosine at carbon electrodes has been studied. The initial electrochemical event is a 1e-, 1H+ oxidation to give free radicals which undergo a series of follow-up chemical and electrochemical reactions which lead to formation of a new class of purine oligonucleosides.     

Transglycosylation Reactions of Purine Nucleosides. A Review

Abstract

Mechanism, regio- and stereoselectivity, reversibility as well as some practical applications of transglycosylation reactions in the chemistry of purine nucleosides are reviewed. There are two main reaction pathways of glycosylation and transglycosylation in the purine series; i) the better known and generally accepted 3→9 sequence of adenine and its derivatives ii) the equally conceivable 7?9 mechanism for guanine and other 6-oxopurines, which is hereby supported by the author's study.

     

Purine Derivatives of 1,2-Disubstituted Cyclohexane Analogues of Nucleosides

Abstract

Starting from (±)-cis-2-hydroxymethylcyclohexylamine, a series of cyclohexane-derived cis-1,2-disubstituted carbonucleoside analogues with a 6- or 2,6-purine or 8-azapurine base were synthesized. The antiviral and antitumoral in vitro effects of the new compounds were evaluated.     

Synthesis of 1,5-Anhydro-D-Mannitol Nucleosides with a Purine Base Moeety

Abstract

D-Mannitol nucleosides with a purine base moiety have been conveniently synthesized strating from 1,5-anhydro-4,6-O-benzylidene-D-glucitol. The 3-OH function of 1,5-anhydro-4,6-O-benzylidene-D-glucitol was selectively protected with t-butyldimethylsilyl group and subsequently converted to the corresponding 0-triflate derivative for the introduction of the nucleobase moietes. These nucleoside derivatives were transformed to 1,5-Anhydro-6-O-MMTr-2-(N⁶-benzoyladenin-9-yl)-2-deoxy-3-O-TBDMS-D-mannitol and 1,5-Anhydro-6-O-MMTr-2-(N²-isobutyryl-guanin-9-yl)-2-deoxy-3-O-TBDMS-D-mannitol, useful as the building blocks for oligonucleotide synthesis. Also, the synthesis of the corresponding fully deprotected anhydrohexitol nucleosides were achieved for evaluation of antiviral activity test.     

Metabolism of Exogenous Purine Bases and Nucleosides by Salmonella typhimurium

Purine-requiring mutants of Salmonella typhimurium LT2 containing additional mutations in either adenosine deaminase or purine nucleoside phosphorylase have been constructed. From studies of the ability of these mutants to utilize different purine compounds as the sole source of purines, the following conclusions may be drawn. (i) S. typhimurium does not contain physiologically significant amounts of adenine deaminase and adenosine kinase activities. (ii) The presence of inosine and guanosine kinase activities in vivo was established, although the former activity appears to be of minor significance for inosine metabolism. (iii) The utilization of exogenous purine deoxyribonucleosides is entirely dependent on a functional purine nucleoside phosphorylase. (iv) The pathway by which exogenous adenine is converted to guanine nucleotides in the presence of histidine requires a functional purine nucleoside phosphorylase. Evidence is presented that this pathway involves the conversion of adenine to adenosine, followed by deamination to inosine and subsequent phosphorolysis to hypoxanthine. Hypoxanthine is then converted to inosine monophosphate by inosine monophosphate pyrophosphorylase. The rate-limiting step in this pathway is the synthesis of adenosine from adenine due to lack of endogenous ribose-l-phosphate.     

Peroxynitrite Mediated Oxidation of Purine Bases of Nucleosides and Isolated DNA

Reaction of nitric oxide with superoxide anion produces the highly reactive species peroxynitrite (ONOO^?). This compound has been shown to be a strong oxidant of lipids and proteins. However, no data are available on its effect on DNA, with the exception of the induction of strand breaks. We report the result of studies on the reactions of peroxynitrite with the adenine and guanine moieties of nucleosides and isolated DNA. The samples were analyzed for 8-oxo-7,8-dihydro-2′-deoxyguano-sine (8-oxo-dGuo), 2,2-diamino-4–[(2-deoxy-β-D-erythro-pentofuranosyl)amino]-5–(2H)-oxazolone (oxazolone) and 8-oxo-7,8-dihydro-2′-deoxyadenosine (8-oxo-dAdo). The effects of peroxynitrite treatment were compared with those of ionizing radiation in aerated aqueous solution, chosen as a source of hydroxyl radicals. At the nucleoside level, both oxidizing conditions led to the formation of oxazolone and 8-oxo-dAdo. In addition, evidence was provided for the formation of the 4R* and 4S* diastereoisomers of 4-hydroxy-8-oxo-4,8-dihydro-2′-deoxyguanosine. The latter dGuo oxidation products were chosen as markers of the release of singlet oxygen (¹O₂) upon reaction of peroxynitrous acid with hydrogen peroxide. Oxidation of purine bases was then studied within isolated DNA. A significant increase in the level of 8-oxp-dGuo, oxazolone and 8-oxo-dAdo was observed within double stranded DNA upon exposure to γ-radiation. Oxazolone and 8-oxo-dAdo were formed upon peroxynitrite treatment but no significant increase in the amount of 8-oxo-dGuo was detected. These results showed that peroxynitrite exhibits oxidizing properties toward purine moieties both in nucleosides and isolated DNA. However, the significant differences in the oxidative damage distribution within DNA observed after exposure to γ radiation by comparison with peroxynitrite treatment questions the involvement of hydroxyl radicals as the main oxidizing species released by decomposition of peroxynitrous acid.     

Screening of Catalytically Active Microorganisms for the Synthesis of 6-Modified Purine Nucleosides

Modified nucleosides can be prepared by microbial transglycosylation from cheaper nucleoside precursors using free or immobilised whole cells. An efficient screening method to find transglycosylation activity in␣microorganisms was developed for the synthesis of 6-modified purine nucleosides, such as 6-chloro-, 6-methoxy-, 6-iodo- and 6-mercaptopurine ribonucleoside. Out of 100 microorganisms screened, Bacillus stearothermophilus ATCC 12980 was the best for this purpose.     

Differential Sensitivities of Normal and Malignant Murine Lymphocytes to Purine Nucleosides

Abstract

Inherited human immunodeficiences associated with loss of adenosine deaminase or purine nucleoside phosphorylase are thought to result from accumulation of the nucleoside substrates. This work attempts to identify lymphocyte subpopulations that are uniquely-sensitive to the endogenous substrates or their analogs.     

Reactions of Purine Nucleosides with Aqueous Alkalies: The Effect of the C6 Substituent on the Kinetics of the Multistage Pathway

Abstract

Kinetics of the reactions of 6-substituted 9-(β-Q-ribofuranosyl)purines with aqueous alkalies have been studied liquid chromatographicaIly.     

嘌呤核苷及其衍生物的代谢工程

嘌呤核苷及其衍生物被广泛应用于食品和医药领域。利用诱变筛选技术可以获得嘌呤核苷类产品的工业生产菌株,但往往耗时,效率低,而且获得的某些高产菌株还存在不稳定的缺陷。菌株代谢调控与生理生化的研究为代谢工程优化嘌呤核苷类产品的合成提供了理论基础,利用代谢工程改造菌株合成嘌呤核苷也引起了研究人员的关注。系统地介绍了微生物嘌呤生物合成途径及其调控机制,综述了嘌呤核苷类产品及其衍生物的代谢工程研究进展,最后讨论了利用代谢工程改造菌株合成这些产品面临的问题及今后的研究方向。     

Studies on Disaccharide Nucleoside Synthesis. Mechanism of the Formation of Trisaccharide Purine Nucleosides

Abstract

The unexpected formation of trisaccharide nucleosides during synthesis of purine 5′-O-β-D-ribofuranosylnucleosides in the presence of Lewis acids was observed.     

Synthetic and Antiviral Studies of Carboacyclic 6- and 2,6-Substituted Purine Nucleosides

Abstract

Chiral purine derivatives containing a carboacyclic chain mimicking the ribose ring, but lacking the C(3′)-C(4′) bond have been prepared from (2S, 3R)-3-amino-1,2,6-tribenzyloxyhexane 15. The synthesis of this amine via an hex-2-enopyranoside utilizes the absolute configuration defined by carbons 4 and 5 of D-glucose. None of these compounds exhibited any antiviral activity against HIV.     

The Synthesis of Derivatives of 2-Arylamino ara-Carbocyclic Purine Nucleosides as Potential Anti-Viral Agents

Abstract

A general synthetic method into 2-arylamino ara-carbocyclic purine nucleosides from 2,4,6-mchloropyrimidine is described.     

An Assessment of Electronic Properties of Pyrimidine and Purine Nucleosides by 15N-NMR Spectroscopy

Abstract

An ¹⁵N-NMR study at natural abundance of 0⁴/N³-substituted pyrimidine and C⁶-substituted purine ribonucleosides has shown that the exact location of the protecting group (substituent) on either 0⁴ or N³ in pyrimidines has a strong influence on the electronic properties of the resultant pyrimidine system, mainly because of the change of state of hybridization of the N³-nitrogen. The basicity of N³ in some C⁴-substituted pyrimidines has been studied by following the ¹⁵N chemical shifts of protonated species in the presence of CF₃COOH both in DMSO and in CH₂Cl₂ solution. A comparison of the basic character of N³ in C⁴-substituted pyrimidine and of N¹ in C⁶-substituted purine nucleosides has shown that the magnitude of the ¹⁵N shift of N³ (or N¹) upon protonation is governed mainly by the electronic properties of the heteroatom linked to C⁴ (or C⁶). It also clearly emerged in this study that there is very litle difference in basicities of N³ of pyrimidine and N¹ of purine nucleosides despite the presence of the fused imidazole moiety in the latter.     

Nucleosides VI: A Novel and Convenient Synthesis of Purine S-Cyclonucleosides Via Mitsunobu Reaction

Abstract

Two representative S-cyclonucleosides, 8,5′-anhydro-2′, 3′-O-isopropylidene-8-mercaptoadenosine (3) and 8,2′-anhydro-3′,5′-O-(tetraisopropyldisiloxane-1,3-diyl)-8-mercaptoguanosine (8), were prepared in good yields by dropwise addition of one equivalent each of triphenylphosphine and DEAD in DMF into a mixture of 2′,3′-O-isopropylidene-8-mercaptoadenosine (2) or 3′,5′-O-(tetra-iso-propyldisiloxane-1,3-diyl)-8-mercaptoguanosine (7), respectively, in DMF. Treatment of compound 2 with two equivalents each of triphenylphosphine and DEAD in DMF afforded N-[8,5′-anhydro-2′,3′-O-isopropylidene-8-mercaptopurin-6-yl]triphenylphospha-λ5-azene (4) in 87% yield.     

Nucleosides,I Ribosylation of 8-Substituted Theophylline Derivatives

Abstract

The attempted ribosylation reaction of 8-nitro-theophylline (2) with 1-o-acetyl-2, 3, 5-tri-o-benzoyl-D-ribo-furanose (5) failed to give any nucleoside product, whereas the reaction of 8-chlorotheophylline (3) with 5 afforded the 8-chloro-7-(2,3,5-tri-o-benzoyl) β-D-ribofuranosyltheophylline (6) in good yield. The product 6 reacted with benzylamine producing the 8-benzylamino-7-(2, 3, 5-tri-O-benzoyl) β-D-ribo-furanosyltheophylline (10), which could also be synthesised by ribosylation of 8-benzylaminotheophylline (8) with 5. Debenzoylation of 6 and 10 gave the corresponding 7-β-D-ribofuranosyltheophylline nucleosides (7) and (11), respectively. Compound 7 could be converted into 11 by reaction with benzylamine. The newly synthesised compounds have been characterised by elemental analysis, ¹H-NMR and UV spectra.     

The Oxidative Chlorination of Pyrimidine and Purine Bases,and Nucleosides Using Acyl Chloride-Dimethyl-Formamide-m-Chloroperbenzoic Acid System1

Abstract

Pyrimidine and purine bases, and nucleosides were chlorinated by the reaction of acyl chloride in DMF with MCPBA under mild conditions in moderate yields.