ISSN:
1434-193X
Keywords:
Fluorinated dideoxynucleosides
;
Through-space interactions
;
Hydrogen bonds
;
Long-range coupling constants
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
-A collection of 5′-O-benzyl-2′,3′-dideoxy-4′-(fluoromethyl)nucleosides carrying both purinic and pyrimidinic nucleobases (uracil, 5-Br-uracil, 5-O2N-uracil, 6-Cl-purine and inosine) were synthesized in both the α and the β form. Through-space-transmitted 6JCF NMR coupling constants between F and C-6 (pyrimidinic base) or C-8 (purinic base) were observed for all of the α anomers of the compounds examined, whilst the corresponding 7JHF coupling constants were resolved only for the 5-substituted uracil derivatives. The absolute values of all the through-space couplings were found to decrease monotonically with increasing solvent polarity (CDCl3, MeOD, [D6]acetone, [D6]DMSO). This trend suggests that the through-space interaction is mediated by an intramolecular (sp3)C-F…H-C(sp2) hydrogen bond. The possibility of any relevant solvent-induced conformational change influencing the F/base mutual spatial relationship in the molecules investigated was ruled out by heteronuclear steady-state 1H{19F}-NOE experiments. A linear correlation was observed between 6JCF and 7JHF coupling constants and the Kamlet-Taft's hydrogen bond basicity parameter β. The crystal structures of the α and β anomers of the 5-nitrouracil nucleoside show evidence that the H-6 of the nucleobase forms hydrogen-bond-like interactions involving the O-benzyl oxygen atom in the β anomer, and that in the case of the α anomer this is replaced by the F atom of the fluoromethyl group.
Additional Material:
4 Ill.
Type of Medium:
Electronic Resource
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