K. Walczak, M. Wamberg, E. Pedersen
Feb 1, 2004
Citations
0
Influential Citations
10
Citations
Journal
Helvetica Chimica Acta
Abstract
Acyclic nucleosides of 4-nitro-1H-imidazole and 4-nitropyrazole have been synthesized by nucleophilic addition of the appropriate 4-nitroazole to (−)-(S)-(hydroxymethyl)oxirane in the presence of a catalytic amount of potassium carbonate. (+)-(R)-3-(4-nitro-1H-imidazol-1-yl)propane-1,2-diol and (+)-(R)-3-(2-methyl-4-nitro-1H-imidazol-1-yl)propane-1,2-diol were also obtained in an independent reaction starting from appropriate 1,4-dinitro-1H-imidazole and (+)-(R)-3-aminopropane-1,2-diol. (+)-(R)-3-(4-Nitropyrazol-1-yl)propane-1,2-diol was also obtained by direct noncatalyzed addition of 4-nitropyrazole to (−)-(S)-(hydroxymethyl)oxirane, whereas the (S)-enantiomer was obtained by reaction of 4-nitropyrazole with (+)-(S)-1,2-O-isopropylideneglycerol under Mitsunobu reaction conditions, followed by a cleavage of the isopropylidene group with 80% AcOH. Racemization during any of these syntheses has not been observed. 3-(4-Nitroazol-1-yl)propane-1,2-diols were incorporated into a 26-mer oligonucleotide. UV Thermal melting studies of duplexes of the oligonucleotides with 4-nitropyrazole or 4-nitro-1H-imidazole paired with four natural bases showed moderately decreased stabilities of the duplexes. A narrow range of melting temperatures, typically being within 2° for each acyclic nucleoside, fulfill one of the requirements of using acyclic 4-nitroazoles as general bases. Single incorporation of 4-nitroazoles into a 14-mer triplex forming oligonucleotide resulted in considerably decreased triplex stabilities.