Synthesis of 1,14-diamino-5,10-diaza-N1,N14,5,10- tetrakis-/9-(β-d-ribofuranosyl)purin-6-yl/-tetradecane - a new oligonucleotide analogue with stacked base residues
✍ Scribed by Jiří Žemlička
- Publisher
- Elsevier Science
- Year
- 1984
- Tongue
- French
- Weight
- 189 KB
- Volume
- 25
- Category
- Article
- ISSN
- 0040-4039
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✦ Synopsis
The title compound lb was obtained by reaction of rine (2) with N,N'-bis-(4-aminobutyl)-1,4_diaminobutane (3). 6-chloro-9-(B-D-ribofuranosyl)pu-Bridged nucleosides, e.g. compound la, have been studied extensivelyI'I0 and their derivatives, suitably functionalized, have found use as valuable probes for enzymes such as ribosomal peptidyltransferase397, snake venom phosphodiesterase2 and codon-anticodon binding8. Similar dinucleosides linked by a single methylene group were obtained from hydrolysis of DNA and RNA treated with formaldehydell. Spectral6 and enzymic studies23397 have shown that bridged nucleosides containing 2 and 4 methylene groups as spacers can be regarded as analogues of dinucleoside phosphates. The availability of bridged nucleosides has been hitherto restricted to compounds having only two nucleoside residues in the molecule. We have now prepared the first "bridged oligonucleoside" which contains four ribonucleoside moieties linked to a polyamine backbone -compound lb. "Exhaustive nucleosidation" of polyamine 3 with chloro nucleoside 2 (5 molar equivalents) readily afforded product lb in 70% yield (Scheme 1). Compound lb has a plane of symmetry and comprises two different nucleoside residues -N6-mono-and N6-dialkylated adenosine. Thus, the FT-100 NMR spectrum of lb exhibits a pattern of heterocyclic H8 and H2 protons as 2 + 1 singlets at 6 8.36, 8.32 and 8.19 whereas anomeric HI' protons appear as two poorly resolved overlapped doublets centered at 6 5.86. After addition of D20, the pattern of the purine protons was reversed to give 1 + 2 singlets at 6 8.27 and 8.12 (poorly resolved). Integration showed the ratio of (H8 + H2):HI : C-methylene groups ( 6 1.67) being 1.8 : 1 : 3.2 (calculated for structure lb: 2 : 1 : 3).