Synthesis of 4‐Substituted 1H‐Benzimidazole 2′‐Deoxyribonucleosides and Utility of the 4‐Nitro Compound as Universal Base

Abstract

AbstractThe stereoselective synthesis of 4‐substituted 1H‐benzimidazole 2′‐deoxyribonucleosides is described. Regioisomeric (N1 and N3) β‐D‐deoxyribonucleosides 2a–c and 3a–c were formed. 13C‐NMR Chemical shifts of the 1H‐benzimidazole 2′‐deoxy‐β‐D‐ribofuranosides were correlated with point charges of C‐atoms as well as with Hammett constants of the exocyclic substituents. Phosphonate and phosphoramidite building blocks of 4‐nitro‐1H‐benzimidazole 2′‐deoxyribofuranoside (2a) were prepared (see 4a, b). Oligonucleotides of the d(A20) type were synthesized in which the two central dA bases were replaced by 4‐nitro‐1H‐benzimidazole residues. They were hybridized with oligomeric dT and related oligomers having the other conventional bases opposite to the 4‐nitro‐1H‐benzimidazole moieties. Within these duplexes (12·13, 12·14, 12·15, and 12·16), the destabilization was almost independent of the mismatch which is required for a universal base. The thermodynamic data indicate that the 4‐nitro‐1H‐benzimidazole residues do not form H‐bonds with opposite bases but are stabilizing the duplex by stacking interactions and favorable entropic changes.