70184-00-8Relevant academic research and scientific papers
Customizable and Regioselective One-Pot N?H Functionalization of DNA Nucleobases to Create a Library of Nucleobase Derivatives for Biomedical Applications
Borges, Jo?o,Machado, Carmen M.,Mano, Jo?o F.,Rocha, Djenisa H. A.,Silva, Artur M. S.,Silva, Vera L. M.,Sousa, Cristiana F. V.,Sousa, Vera
, p. 4423 - 4433 (2021/08/30)
DNA is one of the most exciting biomolecules in nature for developing supramolecular biofunctional nanoarchitectures owing to the highly specific and selective interactions between complementary Watson-Crick base pairing. Herein, simple and one-pot synthetic procedures have been implemented for producing a library of DNA nucleobase derivatives endowed with reactive functional groups for bioconjugation and cross-linking strategies with other (bio)molecules. Purine and pyrimidine molecules have been regioselectively N?H functionalized either via N-alkylation, N-allylation, N-propargylation or Michael-type reactions and structurally characterized. The influence of the reaction conditions was assessed and discussed. The in vitro biocompatibility of the native and nucleobase derivatives was evaluated by culturing them with human fibroblasts, revealing their cytocompatibility. The library of nucleobase derivatives holds great promise for being coupled to different biomolecules, including biopolymeric materials, lipids, and peptides, thus potentially leading to modular supramolecular nanobiomaterials for biomedicine.
The Convenient Synthesis of Unsaturated Nucleoside Analogues in Water under Microwave Irradiation
Xia, Ran,Sun, Li-Ping
, p. 76 - 82 (2016/03/01)
A convenient method for the regioselective synthesis of unsaturated nucleoside analogs in water under microwave irradiation was developed. All pyrimidine and purine nucleoside derivatives were exclusively alkylated at N1 and N9 respectively in good to excellent yields. In addition, this system could tolerate a broad range of functional groups, such as chloro, bromo, iodo, alkyl, amino, and hydroxyl groups. More importantly, the reaction scale could be enlarged to 50 mmol which made this route attractive for industrial application.
Biomimetic polyorganosiloxanes: Model compounds for new materials
Kociok-Koehn, Gabriele,Mahon, Mary F.,Molloy, Kieran C.,Price, Gareth J.,Prior, Timothy J.,Smith, Douglas R. G.
, p. 7734 - 7746 (2014/05/20)
The chemistry of N-organosilylalkyl-substituted heterocyclic bases (thymine, adenine and cytosine) is described, covering the structures of model compounds, the synthesis of substituted oligo-siloxanes and a preliminary report of the synthesis of a poly(organosiloxane) with pendant N-alkyl(heterocycle) functionalities. N-Alkenylthymines CH2CH(CH2)nT (T = thymine, n = 1 (1), 2 (2), 3 (3)) have been prepared and 2 hydrosilylated to form PhMe2Si(CH2)4T (5). Alternatively, 5 was prepared by reaction of PhMe2Si(CH2)4Br (6) with (O,O-SiMe3)2T, a method which has also been used to prepare PhMe2Si(CH2)4A (7) and PhMe 2Si(CH2)4C (8) (A = adenine, C = cytosine). Model di- and tri-siloxanes [Br(CH2)4(Me) 2Si]2O (10), Me3SiOSi(Me)2(CH 2)4Br (11), PhMe2SiOSi(Me)2(CH 2)4Br (12) and (Me3SiO)2(Me) Si(CH2)4Br (13) have been prepared by hydrosilylation of H2CC(H)(CH2)4Br with an appropriate hydrosiloxane and used to prepare Me3SiO(Me)2Si(CH 2)4T (14), Me3SiO(Me)2Si(CH 2)4A (15) (both from 11), and (Me3SiO) 2(Me)Si(CH2)4T (16), (Me3SiO) 2(Me)Si(CH2)4A (17) (both from 13). 10 reacts with thymine to give a mixture of the pyrimidocyclophane cyclo-T-N,N-[(CH 2)4(Me)2Si]2O (19) and [T(CH 2)4Si(Me)2]2O (20), while cytosine reacts similarly to form cyclo-C-N,N-[(CH2)4(Me) 2Si]2O (21; as an imine) and [C(CH2) 4Si(Me)2]2O (22); adenine only generates [A(CH2)4Si(Me)2]2O (18) in an analogous synthesis. Using a related protocol, polymeric {[MeSi(O)(CH 2)4Br]2[Me2SiO]98} n (23) has been converted to {[MeSi(O)(CH2) 4T]2[Me2SiO]98}n (24) and {[MeSi(O)(CH2)4A]2[Me2SiO] 98}n (25). The structures of 4, 5, 8, 19 and 21, along with a 2:1 adduct of 5 with Ni(dithiobiuret)2 (9) are reported. This journal is the Partner Organisations 2014.
Design, synthesis, antiviral, and cytostatic evaluation of novel isoxazolidine analogs of homonucleotides
Lysakowska, Magdalena,Balzarini, Jan,Piotrowska, Dorota G.
, p. 341 - 353 (2014/05/20)
Moderate diastereoselectivities (d.e. 2-62%) of isoxazolidine homonucleotides were observed for cycloadditions between N-methyl-C- (diethoxyphosphoryl)nitrone and N-allyl nucleobases, with trans-isoxazolidines predominating. The stereochemistry of the substituted isoxazolidines was established based on 2D NOE experiments performed for uracil-containing cycloadducts. The cis- and trans-isoxazolidine phosphonates obtained herein were evaluated in vitro for activity against a broad range of DNA and RNA viruses. None of the compounds were endowed with antiviral activity at subtoxic concentrations, but some of them were found to inhibit the proliferation of L1210 cells with IC50 values in the range of 33-100 μM.
Microwave-assisted N-allylation of uracil and thymine pyrimidine bases
Sacarescu,Atudosie,Simionescu,Sacarescu,Harabagiu
experimental part, p. 602 - 606 (2012/01/13)
This work presents a new synthetic approach to N(1)-allylation of pyrimidine nucleobases with allyl bromide. The increased efficiency of the proposed method is based on two specific elements: (a) the nucleoside N-deprotonation is carried out in a homogeneous system by using sodium methylsulfinyl- methylide in DMSO; (b) the allylation reaction is microwave-assisted. This method ensures high yields (87-88%) of the monoallylated products and short reaction time (1.5 h as compared to tens of hours for classical methods), and provides protection against side reactions. NMR analysis of the crude reaction mixture indicated a ratio of 6-8 : 1 between N(1)-allyl derivatives and N(1),N(3)-diallyl derivatives.
One-pot synthesis of n-alkyl purine, pyrimidine and azole derivatives from alcohols using ph3p/ccl4: A rapid route to carboacyclic nucleoside synthesis
Rad, Mohammad Navid Soltani,Khalafi-Nezhad, Ali,Behrouz, Somayeh,Asrari, Zeinab,Behrouz, Marzieh,Aminia, Zohreh
experimental part, p. 3067 - 3076 (2009/12/28)
A facile and efficient method for one-pot N-alkylation of nucleobases and azole derivatives from alcohols using triphenylphosphine in carbon tetrachloride is described. In this method, treatment of alcohols with a mixture of triphenylphosphine, carbon tetrachloride, nucleobase or azole derivatives and potassium carbonate in the presence of catalytic amounts of tetra-n- butylammonium iodide (TBAI) in refluxing N,N-dimethylformamide, furnishes the corresponding N-alkyl derivatives in good yields. This methodology is highly efficient for various structurally diverse primary alcohols and also useful for N-alkylation of other N-heterocycles containing an acidic N-H bond.
One-pot synthesis of N-alkyl purine and pyrimidine derivatives from alcohols using TsIm: a rapid entry into carboacyclic nucleoside synthesis
Soltani Rad, Mohammad Navid,Khalafi-Nezhad, Ali,Behrouz, Somayeh,Faghihi, Mohammad?Ali,Zare, Abdolkarim,Parhami, Abolfath
, p. 1778 - 1785 (2008/09/18)
A convenient and efficient one-pot N-alkylation of nucleobases from alcohols using N-(p-toluenesulfonyl)imidazole (TsIm) is described. In this method, treatment of alcohols with a mixture of purine or pyrimidine nucleobase, TsIm, K2CO3, and triethylamine in refluxing DMF regioselectively furnishes the corresponding N-alkyl nucleobases in good yields. This methodology is highly efficient for various structurally diverse primary alcohols.
Efficient synthesis of various acycloalkenyl derivatives of pyrimidine using cross-metathesis and Pd(0) methodologies
Amblard, Franck,Nolan, Steven P.,Schinazi, Raymond F.,Agrofoglio, Luigi A.
, p. 537 - 544 (2007/10/03)
Novel acyclonucleosides (9a-d, 10a-d, 18a,b and 19a,b) have been prepared using Pd(0) and cross-metathesis methodologies. The allylic N-alkylation under Tsuji-Trost conditions was used to introduce the nucleobase, while the Suzuki-Miyaura reaction afforded C-5 substituted uracil analogues. The cross-metathesis performed with a ruthenium catalyst was used to provide new acycloalkenyl nucleosides. The antiviral activities of all final compounds have been evaluated. Novel acyclonucleosides (9a-d, 10a-d, 18a,b and 19a,b) were prepared using Pd(0) and cross-metathesis methodologies. The allylic N-alkylation under Tsuji-Trost conditions was used to introduce the nucleobase, meanwhile the Suzuki-Miyaura reaction afforded C-5 substituted uracil analogues. A ruthenium-based cross-metathesis reaction was used to synthesize new acycloalkenyl nucleosides.
Regioselective synthesis of 1-allyl- and 1-arylmethyl uracil and thymine derivatives
Malik, Vaishali,Singh, Palwinder,Kumar, Subodh
, p. 4009 - 4014 (2007/10/03)
2,4-Bis(trimethylsiloxy) pyrimidines 1 with allyl halides and arylmethyl halides in 1,2-dichloroethane in the presence of I2 regioselectively provide 1-allyl-/1-arylmethyl-uracil and thymine derivatives. The secondary aryl alkyl and diaryl meth
A new route to acyclic nucleosides via palladium-mediated allylic alkylation and cross-metathesis
Amblard, Franck,Nolan, Steven P.,Gillaizeau, Isabelle,Agrofoglio, Luigi A.
, p. 9177 - 9180 (2007/10/03)
A method for the syntheses of E-unsaturated acyclic nucleosides via a combination of palladium-catalyzed allylic alkylation and ruthenium-based cross metathesis is described. This approach provides a concise, efficient and reliable route to new nucleoside
