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Experimental Evidence for Intramolecular Attractive Nonbonded C–F…︁H–C Interactions in 2′,3′‐Dideoxy‐4′‐(fluoromethyl)nucleosides – Through‐Space J CF and J HF NMR Coupling Constants, Correlation with Empirical Parameters of Solvent Polarity and Single‐Crystal X‐ray Structures
Author(s) -
Mele Andrea,
Vergani Barbara,
Viani Fiorenza,
Meille Stefano Valdo,
Farina Alessandra,
Bravo Pierfrancesco
Publication year - 1999
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/(sici)1099-0690(199901)1999:1<187::aid-ejoc187>3.0.co;2-r
Subject(s) - chemistry , nucleobase , hydrogen bond , intramolecular force , uracil , solvent effects , anomer , stereochemistry , sulfonium , heteronuclear molecule , solvent , crystallography , nuclear magnetic resonance spectroscopy , computational chemistry , molecule , organic chemistry , dna , salt (chemistry) , biochemistry
A collection of 5′‐ O ‐benzyl‐2′,3′‐dideoxy‐4′‐(fluoromethyl)nucleosides carrying both purinic and pyrimidinic nucleobases (uracil, 5‐Br‐uracil, 5‐O 2 N‐uracil, 6‐Cl‐purine and inosine) were synthesized in both the α and the β form. Through‐space‐transmitted 6 J CF 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 7 J HF 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 (CDCl 3 , MeOD, [D 6 ]acetone, [D 6 ]DMSO). This trend suggests that the through‐space interaction is mediated by an intramolecular (sp 3 )C–F…H–C(sp 2 ) 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 1 H{ 19 F}‐NOE experiments. A linear correlation was observed between 6 J CF and 7 J HF 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.