2-Amino-8-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)imidazo[1,2-a][1,3,5]triazin-4(8H)-one monohydrate, a 2'-deoxyguanosine analogue with an altered Watson-Crick recognition site.

The title compound, C(10)H(12)FN(5)O(4).H(2)O, shows an anti glycosyl orientation [chi = -123.1 (2) degrees]. The 2-deoxy-2-fluoroarabinofuranosyl moiety exhibits a major C2'-endo sugar puckering (S-type, C2'-endo-C1'-exo, (2)T(1)), with P = 156.9 (2) degrees and tau(m) = 36.8 (1) degrees , while in solution a predominantly N conformation of the sugar moiety is observed. The conformation around the exocyclic C4'-C5' bond is -sc (trans, gauche), with gamma = -78.3 (2) degrees. Both nucleoside and solvent molecules participate in the formation of a three-dimensional hydrogen-bonding pattern via intermolecular N-H...O and O-H...O hydrogen bonds; the N atoms of the heterocyclic moiety and the F substituent do not take part in hydrogen bonding.

Pyrazolo[3,4-d][1,2,3]triazine DNA: synthesis and base pairing of 7-deaza-2,8-diaza-2'-deoxyadenosine.

7-deaza-2,8-diaza-2'-deoxyadenosine (4) was synthesized from 8-aza-7-deaza-2'-deoxyadenosine (1) via the 1,N(6)-etheno derivative 5. Ring opening with sodium hydroxide followed by ring closure in the presence of sodium nitrite formed the tricyclic intermediate 5 from which the transiently introduced "etheno" moiety was removed with NBS. Compound 4 was converted to the phosphoramidite 11, which was employed in solid-phase oligonucleotide synthesis. Base pairing studies on 4, incorporated in a 12-mer duplex, showed that this adenine nucleoside analogue forms a strong base pair with dG but not with dT. This novel base pair is as stable as that of the canonical dA-dT pair. As a result of the absence of nitrogen-7 compound 4 is expected to form a face to face base pair with dG.

Enantioseparation of new nucleoside analogs, related to d4T and acyclovir, by chiral capillary electrophoresis using highly sulfated beta-cyclodextrins.

Baseline separation of some new acyclic nucleosides which are potential antiviral agents was achieved using cyclodextrin capillary zone electrophoresis (CD-CZE). A method for the enantiomeric resolution of these compounds and determination of their enantiomeric purity was developed using anionic CDs (highly sulfated-CD or highly S-CD) as chiral selectors and capillaries, which were dynamically coated with polyethylene oxide (PEO). Operational parameters including (i) the nature and concentration of the chiral selectors, (ii) organic modifiers, (iii) temperature, and (iv) applied voltage were investigated. The use of charged CDs provides (i) a supplementary driving force for the compounds in a running buffer and (ii) enantiomeric resolution by inclusion of compounds in the CD cavity. The highly S-CD was found to be the most effective complexing agent and allowed good enantiomeric resolution. The complete resolution of five nucleoside analogs was obtained using 25 mM phosphate buffer, pH 2.5, containing either highly S-alpha-CD, S-beta-CD or S-gamma-CD at 30 degrees C with an applied field of 0.30 kV/cm. The apparent association constants of the inclusion complexes were calculated. The enantiomer migration order for the molecules investigated was determined and the detection limit of enantiomeric impurities was found to vary between 0.34 to 3.56 ng.mL(-1) for the first enantiomer.

Determination of the enantiomeric purity of nucleoside analogs related to d4T and acyclovir, new potential antiviral agents, using liquid chromatography on cellulose chiral stationary phases.

We reported a method of determination of enantiomeric purity of the new potential antiviral agents by direct analytical HPLC. Those agents are nucleoside analogs, having one chiral center. They are synthesized as a single enantiomer (R or S) by an asymmetric pathway. The chiral stationary phases chosen are silica-based cellulose tris-3,5-dimethylphenylcarbamate (Chiralcel OD-H), or tris-methylbenzoate (Chiralcel OJ). Resolution was achieved using normal-phase chromatography with a mobile phase consisting of n-hexane-alcohol (ethanol or 2-propanol) in various percentages. Furthermore the effects of structural features on retention, selectivity and resolution, as well as on the elution order were thoroughly studied. Differences in the lipophilicity of the compounds were also examined.