Novel modified purine derivatives (bases or nucleosides) bearing C-substituents in position(s) 6, 2 and/or 8 were prepared by Pd- or Fe-catalyzed cross-coupling reactions of halopurines with organometallics. Reactions of di- and trihalopurines are regioselective and applicable to the synthesis of di- or trisubstituted purines bearing different substituents. Cross-coupling reactions of protected functionalized organometallics were used for the preparation of purines bearing functionalized C-substituents. Some of the title modified purine bases and nucleosides display cytostatic activity.

• MeSH
• nukleosidy chemická syntéza   chemie   farmakologie   MeSH
• organokovové sloučeniny chemie   MeSH
• protinádorové látky chemická syntéza   chemie   farmakologie   MeSH
• puriny chemická syntéza   chemie   farmakologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nukleosidy MeSH
• organokovové sloučeniny MeSH
• protinádorové látky MeSH
• puriny MeSH

Simplifying access to synthetic nucleosides is of interest due to their widespread use as biochemical or anticancer and antiviral agents. Herein, a direct stereoselective method to access an expansive range of both natural and synthetic nucleosides up to a gram scale, through direct glycosylation of nucleobases with 5-O-tritylribose and other C5-modified ribose derivatives, is discussed in detail. The reaction proceeds through nucleophilic epoxide ring opening of an in situ formed 1,2-anhydrosugar (termed "anhydrose") under modified Mitsunobu reaction conditions. The scope of the reaction in the synthesis of diverse nucleosides and other 1-substituted riboside derivatives is described. In addition, a mechanistic insight into the formation of this key glycosyl donor intermediate is provided.

• Klíčová slova
• epoxides, glycosylation, nucleosides, riboses, synthesis design,
• MeSH
• antivirové látky chemická syntéza   chemie   MeSH
• epoxidové sloučeniny chemická syntéza   chemie   MeSH
• glykosylace MeSH
• molekulární modely MeSH
• nukleosidy chemická syntéza   chemie   MeSH
• protinádorové látky chemická syntéza   chemie   MeSH
• ribosa analogy a deriváty   chemická syntéza   MeSH
• stereoizomerie MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antivirové látky MeSH
• epoxidové sloučeniny MeSH
• nukleosidy MeSH
• protinádorové látky MeSH
• ribosa MeSH

Modified 2'-deoxynucleosides and deoxynucleoside triphosphates (dNTPs) bearing anthraquinone (AQ) attached through an acetylene or propargylcarbamoyl linker at the 5-position of pyrimidine (C) or at the 7-position of 7-deazaadenine were prepared by Sonogashira cross-coupling of halogenated dNTPs with 2-ethynylanthraquinone or 2-(2-propynylcarbamoyl)anthraquinone. Polymerase incorporations of the AQ-labeled dNTPs into DNA by primer extension with KOD XL polymerase have been successfully developed. The electrochemical properties of the AQ-labeled nucleosides, nucleotides, and DNA were studied by cyclic and square-wave voltammetry, which show a distinct reversible couple of peaks around -0.4 V that make the AQ a suitable redox label for DNA.

• MeSH
• anthrachinony chemie   MeSH
• barvení a značení metody   MeSH
• DNA-dependentní DNA-polymerasy chemie   metabolismus   MeSH
• DNA chemie   MeSH
• elektrochemie MeSH
• molekulární struktura MeSH
• nukleosidy chemie   metabolismus   MeSH
• nukleotidy chemie   metabolismus   MeSH
• oligonukleotidy chemie   metabolismus   MeSH
• oxidace-redukce MeSH
• sekvence nukleotidů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anthrachinony MeSH
• DNA-dependentní DNA-polymerasy MeSH
• DNA MeSH
• nukleosidy MeSH
• nukleotidy MeSH
• oligonukleotidy MeSH

The aim of this article is to study the modification of an inner capillary wall with sol-gel coating (pure silica sol-gel or silica sol-gel containing porphyrin-brucine conjugate) and determine its influence on the separation process using capillary electrophoresis/electrochromatography method. After modification of the inner capillary surface the separation of analytes was performed using two different phosphate buffers (pH 2.5 and 9.0) and finally the changes in electrophoretic mobilities of various samples were calculated. To confirm that the modification of the inner capillary surface was successful, the parts of the inner surfaces of capillaries were observed using scanning electron microscopy. The analytes used as testing samples were oligopeptides, nucleosides, nucleobases and finally nucleotides.

• Klíčová slova
• Capillary electrochromatography (CEC), Nucleo-compounds, Oligopeptides, Open-tubular capillary electrochromatography (OT-CEC), Porphyrin, Scanning electron microscopy (SEM), Sol–gel methods,
• MeSH
• chemické techniky analytické přístrojové vybavení   metody   MeSH
• kapilární elektrochromatografie * MeSH
• mikroskopie elektronová rastrovací MeSH
• nukleosidy izolace a purifikace   MeSH
• nukleotidy izolace a purifikace   MeSH
• oligopeptidy izolace a purifikace   MeSH
• změna skupenství MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nukleosidy MeSH
• nukleotidy MeSH
• oligopeptidy MeSH

D-xylofuranosyl nucleoside analogues bearing alkylthio and glucosylthio substituents at the C3'-position were prepared by photoinitiated radical-mediated hydrothiolation reactions from the corresponding 2',5'-di-O-silyl-3'-exomethylene uridine. Sequential desilylation and 5'-O-butyrylation of the 3'-thiosubstituted molecules produced a 24-membered nucleoside series with diverse substitution patterns, and the compounds were evaluated for their in vitro antiviral activity against three dangerous human RNA viruses, SARS-CoV-2, SINV and CHIKV. Eight compounds exhibited SARS-CoV-2 activity with low micromolar EC50 values in Vero E6 cells, and two of them also inhibited virus growth in human Calu cells. The best anti-SARS-CoV-2 activity was exhibited by 2',5'-di-O-silylated 3'-C-alkylthio nucleosides. Twelve compounds showed in vitro antiviral activity against CHIKV and fourteen against SINV with low micromolar EC50 values, with the 5'-butyryl-2'-silyl-3'-alkylthio substitution pattern being the most favorable against both viruses. In the case of the tested nucleosides, removal of the 2'-O-silyl group completely abolished the antiviral activity of the compounds against all three viruses. Overall, the most potent antiviral agent was the disilylated 3'-glucosylthio xylonucleoside, which showed excellent and specific antiviral activity against SINV with an EC50 value of 3 μM and no toxic effect at the highest tested concentration of 120 μM.

• Klíčová slova
• Chikungunya virus (CHIKV), Nucleoside analogue antivirals, Photochemical thiol-ene reaction, Severe acute respiratory syndrome coronavirus (SARS-CoV-2), Sindbis virus (SINV),
• MeSH
• antivirové látky * farmakologie   chemická syntéza   chemie   MeSH
• Cercopithecus aethiops MeSH
• lidé MeSH
• nukleosidy * farmakologie   chemická syntéza   chemie   MeSH
• RNA-viry * účinky léků   MeSH
• SARS-CoV-2 účinky léků   MeSH
• Vero buňky MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antivirové látky * MeSH
• nukleosidy * MeSH

Three types of sugar modified pyrimido[4,5-b]indole nucleosides (2'-deoxy-2'-fluororibo-, 2'-deoxy-2'-fluoroarabino- and arabinonucleosides) were synthesized by glycosylation of 4,6-dichloropyrimido[4,5-b]indole followed by modification of sugar moiety and introduction of substituents into position 4 by cross-coupling reactions or nucleophilic substitutions. Some 2'-fluororibo- and 2'-fluoroarabinonucleosides displayed interesting anti-HCV activities (IC50 = 1.6-20 μM) and the latter compounds also some anti-dengue activities (IC50 = 10.8-40 μM).

• Publikační typ
• časopisecké články MeSH

New, improved methods to access nucleosides are of general interest not only to organic chemists but to the greater scientific community as a whole due their key implications in life and disease. Current synthetic methods involve multistep procedures employing protected sugars in the glycosylation of nucleobases. Using modified Mitsunobu conditions, we report on the first direct glycosylation of purine and pyrimidine nucleobases with unprotected D-ribose to provide β-pyranosyl nucleosides and a one-pot strategy to yield β-furanosides from the heterocycle and 5-O-monoprotected D-ribose.

• MeSH
• glykosylace MeSH
• molekulární struktura MeSH
• nukleosidy chemická syntéza   chemie   MeSH
• puriny chemie   MeSH
• pyrimidiny chemie   MeSH
• ribosa analogy a deriváty   chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nukleosidy MeSH
• purine MeSH Prohlížeč
• puriny MeSH
• pyrimidine MeSH Prohlížeč
• pyrimidiny MeSH
• ribosa MeSH

Substitution of exocyclic oxygen with sulfur was shown to substantially influence the properties of RNA/DNA bases, which are crucial for prebiotic chemistry and photodynamic therapies. Upon UV irradiation, thionucleobases were shown to efficiently populate triplet excited states and can be involved in characteristic photochemistry or generation of singlet oxygen. Here, we show that the photochemistry of a thionucleobase can be considerably modified in a nucleoside, that is, by the presence of ribose. Our transient absorption spectroscopy experiments demonstrate that thiocytosine exhibits 5 times longer excited-state lifetime and different excited-state absorption features than thiocytidine. On the basis of accurate quantum chemical simulations, we assign these differences to the dominant population of a shorter-lived triplet nπ* state in the nucleoside and longer-lived triplet ππ* states in the nucleobase. This explains the distinctive photoanomerziation of thiocytidine and indicates that the nucleoside will be a less efficient phototherapeutic agent with regard to singlet oxygen generation.

• MeSH
• fotochemické procesy * MeSH
• nukleosidy chemie   MeSH
• ribosa chemie   MeSH
• síra chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• nukleosidy MeSH
• ribosa MeSH
• síra MeSH

7-Deazapurine (pyrrolo[2,3-d]pyrimidine) nucleosides are important analogues of biogenic purine nucleosides with diverse biological activities. Replacement of the N7 atom with a carbon atom makes the five-membered ring more electron rich and brings a possibility of attaching additional substituents at the C7 position. This often leads to derivatives with increased base-pairing in DNA or RNA or better binding to enzymes. Several types of 7-deazapurine nucleosides with potent cytostatic or cytotoxic effects have been identified. The most promising are 7-hetaryl-7-deazaadenosines, which are activated in cancer cells by phosphorylation and get incorporated both to RNA (causing inhibition of proteosynthesis) and to DNA (causing DNA damage). Mechanism of action of other types of cytostatic nucleosides, 6-hetaryl-7-deazapurine and thieno-fused deazapurine ribonucleosides, is not yet known. Many 7-deazaadenosine derivatives are potent inhibitors of adenosine kinases. Many types of sugar-modified derivatives of 7-deazapurine nucleosides are also strong antivirals. Most important are 2'-C-methylribo- or 2'-C-methyl-2'-fluororibonucleosides with anti-HCV activities (several compounds underwent clinical trials). Some underexplored areas of potential interest are also outlined.

• Klíčová slova
• antivirals, cytostatics, deazapurines, nucleosides, nucleotides,
• MeSH
• antivirové látky chemická syntéza   chemie   farmakologie   MeSH
• buňky A549 MeSH
• buňky Hep G2 MeSH
• HeLa buňky MeSH
• lidé MeSH
• nukleosidy chemická syntéza   chemie   farmakologie   MeSH
• protinádorové látky chemická syntéza   chemie   farmakologie   MeSH
• puriny chemie   MeSH
• racionální návrh léčiv MeSH
• screeningové testy protinádorových léčiv MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• 7-deazapurine MeSH Prohlížeč
• antivirové látky MeSH
• nukleosidy MeSH
• protinádorové látky MeSH
• puriny MeSH

Nucleosides and 2'-deoxyribonucleoside triphosphates (dNTPs) bearing phenothiazine (PT) attached to a nucleobase (cytosine or 7-deazaadenine) either directly or through an acetylene linker were prepared through Suzuki or Sonogashira cross-coupling and triphosphorylation, and were studied as building blocks for polymerase construction of modified DNA. The directly PT-substituted dNTPs were better substrates for polymerases than the alkyne-linked dNTPs but all of them were used in enzymatic synthesis of DNA using primer extension, nicking enzyme amplification, PCR or 3'-tail labelling by terminal deoxynucleotidyl transferase. The phenothiazine served as an oxidizable redox label (giving two analytically useful signals of oxidation on electrode) for nucleosides and DNA and was also used in orthogonal combination with previously developed benzofurazane or nitrophenyl labels for redox coding of DNA bases. Therefore, the title PT-linked dNTPs are useful additions to the portfolio of nucleotides for enzymatic synthesis of redox-labelled DNA for electrochemical analysis.

• MeSH
• barvení a značení MeSH
• DNA chemie   genetika   MeSH
• elektrochemie MeSH
• fenothiaziny chemie   MeSH
• konformace nukleové kyseliny MeSH
• molekulární modely MeSH
• nukleosidy chemie   MeSH
• nukleotidy chemie   MeSH
• oxidace-redukce MeSH
• sekvence nukleotidů MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA MeSH
• fenothiaziny MeSH
• nukleosidy MeSH
• nukleotidy MeSH
• phenothiazine MeSH Prohlížeč