Synthesis of Several Novel Symmetrical Amide-Linked Tetra-Benzimidazoles as Promising DNA and/or RNA Binders.

ABSTRACT

Several symmetrical tetrameric benzimidazoles (dimeric-bisbenzimidazoles) were synthesized efficiently in good yields, characterized physicochemically and also by 1H-NMR 13C-NMR, IR, MS, and elemental analysis. Six tetrameric symmetrical benzimidazole were synthesized by varying the amide linkage between the positions C2 and C5 of the benzimidazoles as the sites for building blocks. The benzimidazole units were coupled using (EDC/HOBt) to afford amide-linked 525L525 and 5L25L52L5 (2 and 5 are related to the numbering on benzimidazole ring while L is related to linkage between benzimidazole units) benzimidazole tetramers. Both symmetric dimers; 1,4-bis-(2-carboxybenzimidazolyl)piperazine and 1,4-bis-(2-aminobenzimidazolyl) piperazine were also prepared via condensation of the bis-(1,2-diamine) system using either trichloroacetimidate or 4- nitrobenzoate activation, followed by hydrolysis and reduction respectively. In parallel to the above syntheses, both 5-aminobenzimidazoles and 5-carboxybenzimidazoles were synthesized. Finally; the first set of tetramers was synthesized via coupling of one equivalent of 1,4-bis-(2-aminobenzimidazolyl) piperazine with two equivalents of monomeric 5-carboxybenzimidazole while the second set was achieved by coupling of one equivalent of 1,4-bis-(2-carboxybenzimidazole) piperazine with two equivalents of monomeric 5- aminobenzimidazole.