C-13-ENRICHED RIBONUCLEOSIDES - SYNTHESIS AND APPLICATION OF C-13-H-1 AND C-13-C-13 SPIN-COUPLING CONSTANTS TO ASSESS FURANOSE AND N-GLYCOSIDE BOND CONFORMATIONS

Adenosine (1), cytidine (2), guanosine (3), and uridine (4) have been prepared chemically with 13C enrichment (99 atom%) at Cl' and C2' of the ribose ring. Reliable synthetic protocols have been developed to permit access to millimole quantities of labeled ribonucleosides required for structural studies of stable isotopically labeled oligonucleotides and for in vivo metabolism studies. High-resolution 1Hand 13C NMR spectra of the enriched ribonucleosides have been obtained, and 13C-13C and 13C-1H spin-coupling constants have been measured for pathways within the β-D-ribofuranose ring and across the N-glycoside bond. Related couplings were determined in methyl α- and β-D-ribofuranosides (5,6), and in two conformationally constrained nucleosides, 2,2'-anhydro-(1-α-D-arabinofuranosyl)uracil (7) and 2',3'-Oisopropylidene-2,5'-0-cyclouridine (8). The latter data were used to construct a crude Karplus curve for the 13C-C-N-13C coupling pathway across the N-glycoside bond in 1-4. 1H-1H, 13C-1H, and 13C-13C coupling data are used to evaluate current models describing the conformational dynamics of 1-4 in aqueous solution. © 1990, American Chemical Society. All rights reserved.