Multi-fluorous blockmer for oligonucleotide synthesis, and oligonucleotide synthesis method using the same

A 5′-end-protected nucleoside phosphoramidite for oligonucleotide synthesis represented by formula (II):

• wherein B is a natural nucleoside base;
• R1 is a protecting group that can be removed for deprotection under acidic, basic, or neutral conditions;
• R3 is a protecting group for a phosphate group, or is taken together with one of the groups of R4 bonding to the nitrogen atom bonding to the phosphorus atom to form a ring;
• R4 is a substituted or unsubstituted aliphatic group or a substituted or unsubstituted aromatic group;
• F-protector is O(CH2)n(CF2)mCF3 when the protected moiety of nucleoside base B is O, and is NH(C═O)(CH2)n(CF2)mCF3 when the protected moiety of nucleoside base B is N, wherein n is 1 or 2 and m is an integer of 1 to 20;
• Y is H, OH, a halogen, OCH3, methoxyethyl, CN, CF3, or a hydroxy group protected with an acyl protecting group, an ether protecting group, or a silyl protecting group;
• and Z is H, an alkyl, an O-alkyl, an N-alkyl, or a halogen, or forms a Z—Y bond with Y.

A fluorous blockmer phosphoramidite for oligonucleotide synthesis represented by formula (III):

• wherein B is a natural nucleoside base;
• R1 is a protecting group that can be removed for deprotection under acidic, basic, or neutral conditions;
• R3 is a protecting group for a phosphate group, or is taken together with one of the groups of R5 bonding to the nitrogen atom bonding to the phosphorus atom forming the phosphoramidite moiety to form a ring;
• R5 is a substituted or unsubstituted aliphatic group or a substituted or unsubstituted aromatic group;
• Pro is a protecting group for a nucleoside base, or F-protector, wherein F-protector is O(CH2)n(CF2)mCF3 when the protected moiety of nucleoside base B is O, and is NH(C═O)(CH2)n(CF2)mCF3 when the protected moiety of nucleoside base B is N, wherein n is 1 or 2 and m is an integer of 1 to 20;
• X is O or S;
• p is an integer of 0 to 27;
• Y is H, OH, a halogen, OCH3, methoxyethyl, CN, CF3, or a hydroxy group protected with an acyl protecting group, an ether protecting group, or a silyl protecting group;
• Z is H, an alkyl, an O-alkyl, an N-alkyl, or a halogen, or forms a Z—Y bond with Y;
• and the fluorous blockmer phosphoramidite has at least one group of F-protector at any of the groups of Pro, R1, and R3.

A multi-fluorous blockmer for oligonucleotide synthesis represented by formula (IV):

• wherein B is a natural nucleoside base;
• R1 is a protecting group that can be removed for deprotection under acidic, basic, or neutral conditions;
• R3 is a protecting group for a phosphate group;
• Pro is a protecting group for a nucleoside base, or F-protector, wherein F-protector is O(CH2)n(CF2)mCF3 when the protected moiety of nucleoside base B is O, and is NH(C═O)(CH2)n(CF2)mCF3 when the protected moiety of nucleoside base B is N, wherein n is 1 or 2 and m is an integer of 1 to 20;
• X is O or S;
• 1 is an integer of 0 to 58;
• R7 is (C═O)(CH2)2(C═O)(CH2)n(CF2)mCF3 or a silyl protecting group, wherein n is 1 or 2 and m is an integer of 1 to 20;
• Y is H, OH, a halogen, OCH3, methoxyethyl, CN, CF3, or a hydroxy group protected with an acyl protecting group, an ether protecting group, or a silyl protecting group;
• Z is H, an alkyl, an O-alkyl, an N-alkyl, or a halogen, or forms a Z—Y bond with Y;
• and the multi-fluorous blockmer has at least one group of F-protector at any of the groups of Pro, R1, and R3.