5′-cyclo-phosphonate modified nucleotides

A compound having the structure of Formula I-b or Formula II-b:

• wherein,
• D is O or S;
• X is a 9-purinyl or 1-pyrimidinyl base:
• Z is H, —OH, F, OCH3, —O—(CH2)2—OCH3 or halogen;
• Y1, Y2, Y3, and Y4 are each, independently, H, halogen, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, or C2-C6 alkynyl,
• J is O or S;
• K and L are each independently selected from OH, OR16, SR16, or NR16, wherein R16 is selected from H, C1-C10 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, or
• wherein R14 is selected from H or C1-C4 alkyl optionally substituted with one to three substituents independently selected from SH, S—(C1-C4 alkyl), amino, hydroxyl, oxo or —NH—C═(NH)NH2, and R15 is selected from H, or C1-C18 alkyl;
• Q is a divalent moiety selected from O, S, N(R30), or C(R31)(R32), wherein R30 is H, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, or C2-C6 alkynyl, and R31 and R32 are each, independently, H, halogen, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, or C2-C6 alkynyl;
• and
• A comprises a substituent derived from a phosphate or phosphorothioate moiety of an RNAi agent;
• and
• G1, G2, G3 and G4 are each H.

A compound having Formula I-b-5 or Formula II-b-5:

• wherein,
• D is O or S,
• X is a 9-purinyl or 1-pyrimidinyl base;
• Z is H, —OH, F, OCH3, —O—(CH2)2—OCH3 or halogen;
• Y1, Y2, Y3, and Y4 are each, independently, H, halogen, C1-C6 alkyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkenyl, C2-C6 alkynyl, or C2-C6 alkynyl;
• J is O or S;
• K and L are each independently selected from OH, OR16, SR16, or NR16, wherein R16 is selected from H, C1-C10 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl, or
• wherein R14 is selected from H or C1-C4 alkyl optionally substituted with one to three substituents independently selected from SH, S—(C1-C4 alkyl), amino, hydroxyl, oxo or —NH—C═(NH)NH2, and R15 is selected from H, or C1-C18 alkyl;
• and
• G1, G2, G3 and G4 are each independently selected from the group consisting of H, F, halogen, C1-C6 alkyl, CN, CH2(R33), CH2—O—(R33), C(═O)(R33), C(═S)(R33), or (R34)(R33), wherein R33 is O(R35), S(R35), or N(R35)(R36), wherein R34, R35, and R36 are each independently selected from H, halogen, or C1-C6 alkyl.

A compound having Formula III-b or Formula IV-b:

• wherein:
• X is a 9-purinyl or 1-pyrimidinyl base;
• Z is H, —OH, F, OCH3, —O—(CH2)2—OCH3 or halogen;
• J and J′ are each independently O or S;
• and
• comprises a substituent derived from an RNAi agent.