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

Abstract

Abstract The stereoselective synthesis of 4‐substituted 1 H ‐benzimidazole 2′‐deoxyribonucleosides is described. Regioisomeric ( N 1 and N 3 ) β‐ D ‐deoxyribonucleosides 2a–c and 3a–c were formed. 13 C‐NMR Chemical shifts of the 1 H ‐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‐1 H ‐benzimidazole 2′‐deoxyribofuranoside ( 2a ) were prepared (see 4a, b ). Oligonucleotides of the d(A 20 ) type were synthesized in which the two central dA bases were replaced by 4‐nitro‐1 H ‐benzimidazole residues. They were hybridized with oligomeric dT and related oligomers having the other conventional bases opposite to the 4‐nitro‐1 H ‐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‐1 H ‐benzimidazole residues do not form H‐bonds with opposite bases but are stabilizing the duplex by stacking interactions and favorable entropic changes.