3444-09-5Relevant articles and documents
Synthesis of C-4′Truncated Phosphonated Carbocyclic 2′-Oxa-3′-azanucleosides as Antiviral Agents
Piperno, Anna,Giofre, Salvatore V.,Iannazzo, Daniela,Romeo, Roberto,Romeo, Giovanni,Chiacchio, Ugo,Rescifina, Antonio,Piotrowska, Dorota G.
, p. 2798 - 2805 (2010)
A new template of C-4′-truncated phosphonated nucleosides (TPCOANs) has been obtained in good yields according to two different routes which exploit the reactivity of a phosphonated nitrone. The one-step procedure based on the 1,3-dipolar cycloaddition of a phosphonated nitrone with vinyl nucleobases leads to the unnatural α-nucleosides as the main adducts. On the other hand, the target β-anomers have been obtained in high yield by a two-step procedure based on the 1,3-dipolar cycloaddition of a phosphonated nitrone with vinyl acetate followed by nucleosidation reaction. The reactivity of the phosphonated nitrone has been investigated trough quantum mechanical DFT calculations at the B3LYP/D95+(d,p) theory level. Preliminary biological assays show that β-anomers of TPCOANs are able to inhibit the reverse trancriptase of different retroviruses at concentrations in the nanomolar range, with a potency comparable with that of tenofovir.
Telechelic polynorbornenes with hydrogen bonding moieties by direct end capping of living chains
Kurzhals, Steffen,Binder, Wolfgang H.
, p. 5522 - 5532 (2010)
We present two novel symmetric olefins bearing hydrogen bonding moieties for the direct capping of living ring opening metathesis polymerization-chains using Grubbs catalyst 1st-and 3rd-generation. The symmetric olefins are generated via homo metathesis of the corresponding α-olefins under aid of microwave irradiation and are used to prepare polynorbornene-chains (M n = 4,000-10,000 g/mol, Mw/Mn = 1.1-1.4) bearing barbiturate and thymine-moieties. A qualitative and quantitative analysis of the generated polymers is done via MALDI-TOF MS proving the introduction of hydrogen-bonding moieties into the polymer chain and revealing the strong dependence of the desorption on the chemical structure of the different polymer species and high efficiencies for the end group introduction (90-99%). The efficiency of this process depends strongly on the reaction time and the equivalents of terminating agent with respect to the living end. The best results for the end group introduction are achieved by reacting the living chains with an excess of the terminating agent (5-20 equiv) for 100 h.
Total synthesis of (+)-polyoxin J
Ghosh, Arun K.,Wang, Yong
, p. 2789 - 2795 (1999)
Stereoselective total synthesis of (+)-polyoxin J is described. The synthesis was achieved in a convergent manner by coupling protected thymine polyoxin C (19) and 5-O-carbamoyl polyoxamic acid 27 and subsequent removal of the protecting groups. The key steps of the synthesis of protected thymine polyoxin C involved the stereoselective electrophilic epoxidation of E-allyl alcohol 7 derived from isopropylidene D-ribose derivative 5, followed by regioselective epoxide opening of 8 and conversion of resulting azido diol 9 to protected thymine polyoxin C (19). Protected polyoxamic acid 27 was synthesized stereoselectively by utilizing Sharpless epoxidation of tartrate-derived allylic alcohol 20 followed by a regioselective epoxide ring opening with diisopropoxytitanium diazide.
Synthesis of unsaturated silicon analogues of acyclonucleosides
Latxague, Laurent,Thibon, Jacques,Deleris, Gerard
, p. 4025 - 4028 (1998)
Unsaturated acyclic sila-thymidine analogues were prepared in order to improve then rigidity and to seek better pairing with complementary nucleotides.
Stereoselective nucleoside deuteration for NMR studies of DNA
Lukin, Mark,Santos, Carlos De Los
experimental part, p. 562 - 573 (2011/09/20)
A procedure has been elaborated for stereoselective deuterium substitution of one of the diastereotopic 5'-protons in 2'-deoxynucleotides. The synthetic scheme uses the reduction of the 5-oxosugar derivative with deuterated Alpine-Borane. The resulting de
Nucleotide mimics and their prodrugs
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Page 44, (2008/06/13)
The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.
Synthesis and antiviral activity of oxaselenolane nucleosides
Chu,Ma,Olgen,Pierra,Du,Gumina,Gullen,Cheng,Schinazi
, p. 3906 - 3912 (2007/10/03)
As dioxolane and oxathiolane nucleosides have exhibited promising antiviral and anticancer activities, it was of interest to synthesize isoelectronically substituted oxaselenolane nucleosides, in which the 3'-CH2 is replaced by a selenium atom. To study structure-activity relationships, various pyrimidine and purine oxaselenolane nucleosides were synthesized from the key intermediate, (±)-2-benzoyloxymethyl-1,2-oxaselenolane 5-acetate (6). Among the synthesized racemic nucleosides, cytosine and 5-fluorocytosine analogues exhibited potent anti-HIV and anti-HBV activities. It was of interest to obtain the enantiomerically pure isomers to determine if they have differential antiviral activities. However, due to the difficult and time-consuming nature of enantiomeric synthesis, a chiral HPLC separation was performed to obtain optical isomers from the corresponding racemic mixtures. Each pair of enantiomers of Se-ddC and Se-FddC was separated by an amylose chiral column using a mobile phase of 100% 2-propanol. The results indicate that most of the anti-HIV activity of both cytosine and fluorocytosine nucleosides resides with the (-)-isomers.
Chemo-enzymatic synthesis of thymidine 13C-labelled in the 2'- deoxyribose moiety
Ouwerkerk, Niels,Van Boom, Jacques H.,Lugtenburg, Johan,Raap, Jan
, p. 861 - 866 (2007/10/03)
A synthesis of [3',4'-13C2]thymidine (1) is described in which [13C2]acetic acid (2) is converted into the nucleoside in twelve steps with 9% overall yield. D-2-Deoxyribose-5-phosphate aldolase (DERA, EC 4.1.2.4
Nucleic-Acid Analogs with Constraint Conformational Flexibility in the Sugar-Phosphate Backbone 'Tricyclo-DNA' - Part 1: Preparation of [(5′ R,6′ R)-2′-Deoxy-3′,5′-ethano-5′,6′-methano-β-D- ribofuranosyl]thymine and -adenine, and the Corresponding Phosphoramidites for Oligonucleotide Synthesis
Steffens, Ralph,Leumann, Christian
, p. 2426 - 2439 (2007/10/03)
The synthesis of the tricyclo-deoxynucleoside analogs 1 and 2 and of the corresponding cyanoethyl phosphoramidite building blocks 16 and 21 for oligonucleotide synthesis is described. These tricyclic deoxynucleoside analogs differ from the recently introduced bicyclo-deoxynucleosides by an additional cyclopropane unit joined to the centers C(5′) and C(6′) of the latter (see Fig. 1), and thus represent a further member of the class of nucleoside analogs with constraint conformational flexibility. The synthesis of the tricyclo-deoxynucleosides was achieved by a diastereoselective carbene addition to the enantiomerically pure silyl enol either 8/9 and a Vorbru?ggen condensation of the tricyclic carbohydrate unit 10/11 with in situ persilylated thymine and N6-benzoyladenine. Selective tritylation of the tertiary OH-C(5′) and phosphinylation of OH-C(3′) of 1 and 2 afforded the corresponding phosphoramidites 16 and 21. The 'exo'-configuration of the newly introduced cyclopropane ring was confirmed by 1H-NMR-NOE spectroscopy. The α-D- and β-D-configuration at C(1′) of the nucleoside analogs 1 and 14 (2 and 19, resp.) was assigned by 1H-NMR-NOE spectroscopy and NOESY. Modeling studies of the β-D-anomeric nucleoside analog 1 indicate a preference for the 2′-endo-conformation of the furanose ring and a partial correction of the torsion angle γ to the anti-clinal range compared to bicyclo-deoxynucleosides.
Synthesis and biological evaluation of 1',2'-seconucleo-5'-phosphonates
Racha,Vargeese,Vemishetti,El-Subbagh,Abushanab,Panzica
, p. 1130 - 1135 (2007/10/03)
A series of 1',2'-seconucleophosphonate analogues were prepared containing adenine, cytosine, thymine, and uracil as the nucleobase. The synthetic methodology is efficient and uses chloromethyl ethers derived from the chirons diethyl (3S)-(benzyloxy)-(2R)
