Synthesis of 2',4'-BNACOC bearing a purine nucleobase.
Recently, we have synthesized pyrimidine derivatives of 2',4'-BNA(COC) monomer, the sugar conformation of which was restricted in N-form by a seven-membered bridged structure. The oligonucleotides containing these monomers showed high affinity with complementary single-stranded RNA and significant resistance to nuclease degradation. For an application to antisense methodology, it is important to synthesize 2',4'-BNA(COC) monomers bearing a purine nucleobase. However, the formation of methyleneoxymethylene (COC) linkage in the purine derivatives failed under the acidic conditions used for the synthesis of 2',4'-BNA(COC) with pyrimidine nucleobases. After several examinations, we successfully achieved the synthesis of 2',4'-BNA(COC) monomers bearing a purine nucleobase via the formation of COC linkage using Pummerer-type reaction.
Mitsuoka
Yasunori
Y
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Ohnishi
Ryo
R
Hari
Yoshiyuki
Y
Obika
Satoshi
S
Imanishi
Takeshi
T
D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000737:chemistry; D011687:Purines / Q000737:chemistry*
D001952:Bridged-Ring Compounds; D016376:Oligonucleotides, Antisense; D011687:Purines