Nucleoside derivative and use thereof

Abstract

A nucleoside derivative represented below, or a salt thereof.(In (1), R1 represents a hydrogen atom, a hydroxyl group or a protected group, and in (2), X represent a halogen atom. In (1) and (2), R2 and R4 each represent a hydrogen atom, a hydroxyl protecting, phosphate, or protected phosphate group, or —P(═O)nR5R6 (n is 0 or 1, R5 and R6 each representing a hydrogen atom, hydroxyl, protected hydroxyl, mercapto, protected mercapto, lower alkoxy, cyano lower alkoxy, amino or substituted amino group, when n is 1, R5 and R6 are not both hydrogen atoms), R3 represents NHR7 (R7 represents a hydrogen atom, alkyl, alkenyl or protecting group for an amino group), an azide, amidino or guanidino group, each having a linking group (when R7 is hydrogen atom, the linking group is an alkylene group), and B represents any of a purine-9-yl, 2-oxo-pyrimidin-1-yl, substituted purine-9-yl or substituted 2-oxo-pyrimidin-1-yl group.)

1 . An oligonucleotide comprising a nucleoside derivative represented by formula (1) below, or a salt thereof: 
       
         
           
           
               
               
           
         
         wherein:
 R 1  represents a hydrogen atom, a hydroxyl group, a hydroxyl group in which a hydrogen atom is substituted by an alkyl group or alkenyl group, or a protected group; 
 R 2  and R 4  may be the same or different, and each represents:
 a hydrogen atom, 
 a hydroxyl protecting group, 
 a phosphate group, 
 a protected phosphate group, or 
 —P(═O) n R 5 R 6 , wherein:
 n is 0 or 1, and 
 R 5  and R 6  may be the same or different, with each representing a hydrogen atom, hydroxyl group, protected hydroxyl group, mercapto group, protected mercapto group, lower alkoxy group, cyano lower alkoxy group, amino group or substituted amino group, but when n is 1, R 5  and R 6  are not both hydrogen atoms; 
 
 
 R 3  represents:
 NHR 7  wherein R 7  represents a hydrogen atom, an alkyl group, an alkenyl group or a protecting group for an amino group, 
 an azide group, 
 an amidino group, or 
 a guanidino group, 
 
 
         each having a linking group, but when R 7  is hydrogen atom or a protecting group for an amino group, the linking group is an alkylene group which has 2 to 3 carbon atoms; and
 B represents a nucleobase. 
 
       
     
     
         2 . The oligonucleotide according to  claim 1 , wherein R 1  represents a protected group. 
     
     
         3 . The oligonucleotide according to  claim 2 , wherein the protected group comprises fluorine. 
     
     
         4 . The oligonucleotide according to  claim 2 , wherein the protected group comprises methyl. 
     
     
         5 . The oligonucleotide according to  claim 1 , wherein said oligonucleotide is selected from the group consisting of a DNA molecule, a RNA molecule, and a duplex comprising a DNA and/or a RNA molecule. 
     
     
         6 . The oligonucleotide according to  claim 1 , wherein said oligonucleotide comprises a nucleoside derivative represented by the structure: 
       
         
           
           
               
               
           
         
         wherein P is a protecting group comprising fluorine. 
       
     
     
         7 . The oligonucleotide according to  claim 1 , wherein said oligonucleotide comprises a nucleoside derivative represented by the structure: 
       
         
           
           
               
               
           
         
       
     
     
         8 . An RNA molecule comprising a nucleoside derivative represented by formula (1) below, or a salt thereof: 
       
         
           
           
               
               
           
         
         wherein:
 R 1  represents a hydrogen atom, a hydroxyl group, a hydroxyl group in which a hydrogen atom is substituted by an alkyl group or alkenyl group, or a protected group; 
 R 2  and R 4  may be the same or different, and each represents:
 a hydrogen atom, 
 a hydroxyl protection group, 
 a phosphate group, 
 a protected phosphate group, or 
 —P(═O) n R 5 R 6 , wherein:
 n is 0 or 1, and 
 R 5  and R 6  may be the same or different, with each representing a hydrogen atom, hydroxyl group, protected hydroxyl group, mercapto group, protected mercapto group, lower alkoxy group, cyano lower alkoxy group, amino group or substituted amino group, but when n is 1, R 5  and R 6  are not both hydrogen atoms; 
 
 
 R 3  represents:
 NHR 7 , wherein R 7  represents a hydrogen atom, an alkyl group, an alkenyl group or a protecting group for an amino group, 
 an azide group, 
 an amidino group, or 
 a guanidino group, 
 
 
         each having a linking group, but when R 7  is hydrogen atom, the linking group is an alkylene group which has 2 to 3 carbon atoms; and
 B represents any of a purine-9-yl group, 2-oxo-pyrimidin-1-yl group, substituted purine-9-yl group or substituted 2-oxo-pyrimidin-1-yl group; and 
 
         wherein said RNA molecule consists of an RNA interference agent. 
       
     
     
         9 . The RNA molecule according to  claim 8 , wherein said RNA molecule consists of a siRNA. 
     
     
         10 . The RNA molecule according to  claim 8 , wherein R 7  represents a hydrogen atom. 
     
     
         11 . The RNA molecule according to  claim 8 , wherein R 1  represents a protected group. 
     
     
         12 . The RNA molecule according to  claim 11 , wherein the protected group comprises fluorine. 
     
     
         13 . The RNA molecule according to  claim 11 , wherein the protected group comprises methyl. 
     
     
         14 . The RNA molecule according to  claim 8 , wherein the nucleoside derivative comprises the structure: 
       
         
           
           
               
               
           
         
       
     
     
         15 . The RNA molecule according to  claim 8 , wherein the nucleoside derivative comprises the structure: 
       
         
           
           
               
               
           
         
         wherein P is a protecting group. 
       
     
     
         16 . The RNA molecule according to  claim 15 , wherein P comprises fluorine.