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Synthesis of 4‐Substituted 1 H ‐Benzimidazole 2′‐Deoxyribonucleosides and Utility of the 4‐Nitro Compound as Universal Base
Author(s) -
Seela Frank,
Bourgeois Werner,
Rosemeyer Helmut,
Wenzel Thomas
Publication year - 1996
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19960790216
Subject(s) - benzimidazole , chemistry , deoxyribonucleosides , stereochemistry , phosphoramidite , nitro , phosphonate , medicinal chemistry , oligonucleotide , organic chemistry , dna , biochemistry , alkyl , enzyme
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.