Modified 5′ diphosphate nucleosides and oligomeric compounds prepared therefrom

1. A compound having Formula I:

wherein:

Bx is a heterocyclic base moiety;

each Pg is a hydroxyl protecting group;

M 1 is H, OH or OR 1 ;

M 2 is OH, OR 1 or N(R 1 )(R 2 );

each R 1 and R 2 is, independently, alkyl or substituted alkyl;

r is 0 or 1;

A is O, S, CR 3 R 4 or N(R 5 );

R 3 and R 4 are each, independently H, halogen, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, substituted C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or substituted C 2 -C 6 alkynyl;

R 5 is H, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl or a protecting group;

Q 1 and Q 2 are each, independently, H, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, substituted C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or substituted C 2 -C 6 alkynyl;

G is H, OPg, halogen or O—[C(R 6 )(R 7 )] n —[(C═O) m —X] j —Z;

each R 6 and R 7 is, independently, H, halogen, C 1 -C 6 alkyl or substituted C 1 -C 6 alkyl;

X is O, S or N(E 1 );

Z is H, halogen, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, substituted C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, substituted C 2 -C 6 alkynyl or N(E 2 )(E 3 );

E 1 , E 2 and E 3 are each, independently, H, C 1 -C 6 alkyl or substituted C 1 -C 6 alkyl;

n is from 1 to about 6;

m is 0 or 1;

j is 0 or 1;

each substituted group consists of one or more optionally protected substituent groups independently selected from H, halogen, OJ 1 , N(J 1 )(J 2 ), ═NJ 1 , SJ 1 , N 3 , CN, OC(=L)J 1 , OC(=L)N(J 1 )(J 2 ), C(=L)N(J 1 )(J 2 ), C(=L)N(H)—(CH 2 ) 2 N(J 1 )(J 2 ) and a mono or poly cyclic ring system;

L is O, S or NJ 3 ;

each J 1 , J 2 and J 3 is, independently, H or C 1 -C 6 alkyl;

provided that when j is 1 then Z is other than halogen or N(E 2 )(E 3 ); and

provided that when Q 1 and Q 2 are each H and G is H or OPg then A is other than O.

2. The compound of claim 1 wherein Bx is uracilyl, thyminyl, cytosinyl, 5-methylcytosinyl, adeninyl or guaninyl.

3. The compound of claim 2 wherein r is 1, M 1 is H and M 2 is OH.

4. The compound of claim 3 wherein r is 0, M 1 is O(CH 2 ) 2 CN and M 2 is N[CH(CH 3 ) 2 ] 2 .

5. The compound of claim 4 wherein G is halogen, OCH 3 , OCH 2 F, OCHF 2 , OCF 3 , OCH 2 CH 3 , O(CH 2 ) 2 F, OCH 2 CHF 2 , OCH 2 CF 3 , OCH 2 —CH═CH 2 , O(CH 2 ) 2 —OCH 3 , O(CH 2 ) 2 —SCH 3 , O(CH 2 ) 2 —OCF 3 , O(CH 2 ) 3 —N(R 6 )(R 7 ), O(CH 2 ) 2 —ON(R 6 )(R 7 ), O(CH 2 ) 2 —O(CH 2 ) 2 —N(R 6 )(R 7 ), OCH 2 C(═O)—N(R 6 )(R 7 ), OCH 2 C(═O)—N(R 8 )—(CH 2 ) 2 —N(R 6 )(R 7 ) or O(CH 2 ) 2 —N(R 8 )—C(═NR 9 )[N(R 6 )(R 7 )] wherein R 6 , R 7 , R 8 and R 9 are each, independently, H or C 1 -C 6 alkyl.

6. The compound of claim 5 wherein G is halogen, OCH 3 , OCF 3 , OCH 2 CH 3 , OCH 2 CF 3 , OCH 2 —CH═CH 2 , O(CH 2 ) 2 —OCH 3 , O(CH 2 ) 2 —O(CH 2 ) 2 —N(CH 3 ) 2 , OCH 2 C(═O)—N(H)CH 3 , OCH 2 C(═O)—N(H)—(CH 2 ) 2 —N(CH 3 ) 2 or OCH 2 —N(H)—C(═NH)NH 2 .

7. The compound of claim 6 wherein G is F, OCH 3 , O(CH 2 ) 2 —OCH 3 , OCH 2 C(═O)—N(H)CH 3 or OCH 2 C(═O)—N(H)—(CH 2 ) 2 —N(CH 3 ) 2 .

8. The compound of claim 7 wherein G is O(CH 2 ) 2 —OCH 3 .

9. The compound of claim 8 wherein each Pg is, independently, methyl, ethyl, isopropyl, tert-butyl, 2-cyanoethyl, benzyl, phenyl, 4-methoxybenzyl, 4-chlorobenzyl or 2-chlorophenyl.

10. The compound of claim 9 wherein Q 1 and Q 2 are each H.

11. The compound of claim 10 wherein A is CR 3 R 4 .

12. The compound of claim 9 wherein one of Q 1 and Q 2 is H and the other of Q 1 and Q 2 is C 1 -C 6 alkyl.

13. The compound of claim 12 wherein the other of Q 1 and Q 2 is CH 3 .

14. The compound of claim 11 wherein R 3 and R 4 are each H.

15. The compound of claim 11 wherein one of R 3 and R 4 is H provided that the other of R 3 and R 4 is other than H.

16. The compound of claim 15 wherein the other of R 3 and R 4 is CH 3 .

17. The compound of claim 15 wherein the other of R 3 and R 4 is F.

18. The compound of claim 1 having the configuration of Formula Ia:

19. An oligomeric compound comprising a compound having Formula II:

wherein:

Bx is a heterocyclic base moiety;

T 1 is an internucleoside linking group linking the compound of Formula II to the remainder of the oligomeric compound;

each M 3 is, independently, H or a hydroxyl protecting group;

A is O, S, CR 3 R 4 or N(R 5 );

R 3 and R 4 are each, independently H, halogen, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, substituted C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or substituted C 2 -C 6 alkynyl;

R 5 is H, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl or a protecting group;

Q 1 and Q 2 are each, independently, H, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, substituted C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or substituted C 2 -C 6 alkynyl;

G is H, OH, halogen or O—[C(R 6 )(R 7 )] n —[(C═O) m —X] j —Z;

each R 6 and R 7 is, independently, H, halogen, C 1 -C 6 alkyl or substituted C 1 -C 6 alkyl;

X is O, S or N(E 1 );

Z is H, halogen, C 1 -C 6 alkyl, substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, substituted C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, substituted C 2 -C 6 alkynyl or N(E 2 )(E 3 );

E 1 , E 2 and E 3 are each, independently, H, C 1 -C 6 alkyl or substituted C 1 -C 6 alkyl;

n is from 1 to about 6;

m is 0 or 1;

j is 0 or 1;

each substituted group consists of one or more optionally protected substituent groups independently selected from H, halogen, OJ 1 , N(J 1 )(J 2 ), ═NJ 1 , SJ 1 , N 3 , CN, OC(=L)J 1 , OC(=L)N(J 1 )(J 2 ), C(=L)N(J 1 )(J 2 ), C(=L)N(H)—(CH 2 ) 2 N(J 1 )(J 2 ) and a mono or poly cyclic ring system;

L is O, S or NJ 3 ;

each J 1 , J 2 and J 3 is, independently, H or C 1 -C 6 alkyl;

provided that when j is 1 then Z is other than halogen or N(E 2 )(E 3 ); and

provided that when Q 1 and Q 2 are each H and G is H or OH then A is other than O.

20. The oligomeric compound of claim 19 wherein Bx is uracilyl, thyminyl, cytosinyl, 5-methylcytosinyl, adeninyl or guaninyl.