Design and synthesis of new cross-linking agents.
We have previously synthesized 6-vinylated guanosine derivatives by new Pd(0)-catalyzed cross-coupling reaction using guanosine 6-O-tosylate and vinyltributyl-stannane. Its potentials as a cross-linking agent have been demonstrated by adduct formation with guanosine and cytidine. But these 6-vinylated derivatives could not be incorporated to oligonucleotide because of chemical instability. In this paper, we report new deoxyguanosine derivatives with substituted olefin (2 and 3), which were designed to control the reactivity of vinyl functional group. Although either 2 or 3 did not formed the adducts with nucleobases, these compounds reacted with hydroxylamine hydrochloride in the presence of acid catalyst. The reactivity was in the order of 1 > 2 > 3. These results suggest that new guaosine derivatives (2 and 3) have moderate reactivity toward nucleophiles and are expected to be stable in incorporating into oligonucleotides as a cross-linking agent.
Nagatsugi
F
F
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Uemura
K
K
Nakashima
S
S
Maeda
M
M
Sasaki
S
S
D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000737:chemistry*; D015195:Drug Design; D006151:Guanosine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D008722:Methods; D015394:Molecular Structure; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis; D014753:Vinyl Compounds / Q000138:chemical synthesis / Q000737:chemistry
D003432:Cross-Linking Reagents; D016376:Oligonucleotides, Antisense; D014753:Vinyl Compounds; D006151:Guanosine