Supports for oligomer synthesis

1. A compound of formula (II):

wherein:

A is independently selected from hydrogen, a blocking group, SM, L-SM, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aliphatic ether, a substituted or unsubstituted aromatic, a substituted or unsubstituted heteroaromatic; or a substituted or unsubstituted heterocyclic;

SM is a support medium;

L is (C═O)—(CH 2 ) n —(C═O)O—, where n is an integer from 1 to 20;

G 1 is independently selected from O, S, (CR 1 R 2 ) h , NR 3 , O—(C═O), or (C═O)—O;

each of R 1 and R 2 is independently selected from hydrogen, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aromatic, a substituted or unsubstituted heteroaromatic, or a substituted or unsubstituted heterocyclic;

R 3 is independently selected from hydrogen, a blocking group, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aromatic, a substituted or unsubstituted heteroaromatic, or a substituted or unsubstituted hetero cyclic;

each of R U , R V , R W , R X , R Y , and R Z is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

each of Q and W is independently selected from hydrogen, a blocking group, L, SM, L-SM, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, a substituted or unsubstituted heterocyclic, a protected or unprotected nucleosidyl moiety, a protected or unprotected nucleosidyl moiety attached through a phospholinker, or a protected or unprotected oligonucleotidyl moiety;

each of Y 1 and Y 2 is independently selected from O, S, NR 3 , or CR 1 R 2 ; and

h is 1, 2, or 3

wherein at least one of A, Q, and W is SM or L-SM.

2. A compound of claim 1 , wherein for formula (II) when one of A, Q, or W is SM or L-SM, the other two of A, Q or W are not SM or L-SM.

3. A compound of claim 1 , wherein Q and W are each hydrogen and G 1 is O.

4. A compound of claim 1 , wherein one of Q and W is hydrogen and the other is hydrogen or a blocking group, and G 1 , Y 1 and Y 2 are each O.

5. A compound of claim 4 , wherein the blocking group is selected from 4,4′-dimethoxytrityl, monomethoxytrityl, 9-phenylxanthen-9-yl, 9-(p-methoxyphenyl)xanthen-9-yl, t-butyl, t-butoxymethyl, methoxymethyl, tetrahydropyranyl, 1-ethoxyethyl, 1-(2-chloroethoxy)ethyl, 2-trimethylsilylethyl, p-chlorophenyl, 2,4-dinitrophenyl, benzyl, 2,6-dichlorobenzyl, diphenylmethyl, p,p-dinitrobenzhydryl, p-nitrobenzyl, triphenylmethyl, trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, triphenylsilyl, benzoylformate, mesyl, tosyl, 4,4′,4″-tris-(benzyloxy)trityl 4,4′,4″-tris-(4,5-dichlorophthalimido)trityl, 4,4′,4′-tris(levulinyloxy)trityl, 3(imidazolylmethyl)-4,4′-dimethoxytrityl, 4-decyloxytrityl, 4-hexadecyloxytrityl, 9-(4-octadecyloxyphenyl)xanthene-9-yl, 1,1-bis-(4-methoxyphenyl)-1-pyrenylmethyl, p-phenylazophenyloxycarbonyl, 9-fluorenylmethoxycarbonyl, 2,4-dinitrophenylethoxycarbonyl, 4-(methylthiomethoxy)butyryl, 2-(methylthiomethoxymethyl)-benzoyl, 2-isopropylthiomethoxymethyl)benzoyl, 2-(2,4-dinitrobenzenesulphenyloxymethyl)benzoyl, levulinyl, trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, triphenylsilyl, benzoylformyl, acetyl, chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl, pivaloyl, benzoyl, p-phenylbenzoyl, or acetoacetyl.

6. A compound of claim 1 , wherein one of Q and W is (C═O)—(CH 2 ) n —(C═O)O − , wherein n is an integer from 1–20, and the other is a blocking group.

7. A compound of claim 6 , wherein n is 2.

8. A compound of claim 1 , wherein one of Q and W is hydrogen, blocking group, a protected or unprotected nucleosidyl moiety or a protected or unprotected oligonucleotide moiety and the other is selected from L, SM or L-SM.

9. A compound of claim 8 , wherein the blocking group is selected from 4,4′-dimethoxytrityl, monomethoxytrityl, 9-phenylxanthen-9-yl, 9 methoxyphenyl)xanthen-9-yl, t-butyl, t-butoxymethyl, methoxymethyl, tetrahydropyranyl, 1-ethoxyethyl, 1-(2-chloroethoxy)ethyl, 2-trimethylsilylethyl, p-chlorophenyl, 2,4-dinitrophenyl, benzyl, 2,6-dichlorotrityl, diphenylmethyl, p,p-dinitrobenzhydryl, p-nitrobenzyl, triphenylmethyl, trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, triphenylsilyl, benzoylformate, mesyl, tosyl, 4,4′,4″-tris-(benzyloxy)trityl, 4,4′,4″-tris(4,5-dichlorophthalimido)trityl, 4,4′,4″-tris(levulinyloxy)trityl, 3-(imidazolylmethyl)-4,4′-dimethoxytrityl, 4-decyloxytrityl, 4-hexadecyloxytrityl 9-(4-octadecyloxyphenyl)xanthene-9-yl, 1,1-bis-(4-methoxyphenyl)-1′-pyrenylmethyl, p-phenylazophenyloxycarbonyl, 9-fluorenylmethoxycarbonyl, 2,4-dinitrophenylethoxycarbonyl, 4-(methylthiomethoxy)butyryl, 2-(methylthiomethoxymethyl)benzoyl, 2-(isopropylthiomethoxymethyl)benzoyl, 2-(2,4-dinitrobenzenesulphenyloxymethyl)benzoyl, levulinyl, trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, triphenylsilyl, benzoylformyl, acetyl, chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl, pivaloyl, benzoyl, p-phenylbenzoyl, or acetoacetyl.

10. A compound of claim 8 , wherein n is 2.

11. A compound of claim 8 , wherein said support medium is selected from a controlled pore glass, oxalyl-controlled pore glass, silica-containing particles, polymers of polystyrene, copolymers of polystyrene, and divinylbenzene, copolymers of dimethylacrylamide and N,N-bisacryloylethylenediamine, a soluble support medium, or PEPS.

12. A compound of claim 8 , wherein Q is hydrogen, a blocking group, a protected or unprotected nucleosidyl moiety, or a protected or unprotected oligonucleotidyl moiety.

13. A compound of claim 1 , wherein A is selected from a substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, or a substituted or unsubstituted heterocyclic.

14. A compound of claim 13 , wherein A is substituted or unsubstituted aromatic.

15. A compound of claim 14 , wherein A is substituted or unsubstituted phenyl.

16. A compound of claim 1 , wherein one of Q and W is hydrogen, blocking group, a protected or unprotected nucleosidyl moiety or a protected or unprotected oligonucleotidyl moiety and the other is selected from L, SM or L-SM.

17. A compound of claim 16 , wherein the blocking group is selected from 4,4′-dimethoxytrityl, monomethoxytrityl, 9-phenylxanthen-9-yl, 9-(p-methoxyphenyl)xanthen-9-yl, t-butyl, t-butoxymethyl, methoxymethyl, tetrahydropyranyl, 1-ethoxyethyl, 1-(2-chloroethoxy)ethyl, 2-trimethylsilylethyl, p-chlorophenyl, 2,4-dinitrophenyl, benzyl, 2,6-dichlorobenzyl, diphenylmethyl, p,p-dinitrobenzhydryl, p-nitrobenzyl, triphenylmethyl, trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, triphenylsilyl, benzoylformate, mesyl, tosyl, 4,4′,4″-tis (benzyloxy)trityl, 4,4′,4″-tris-(4,5-dichlorophthalimido)trityl, 4,4′,4″-tris(levulinyloxy)trityl, 3-(imidazolylmethyl)-4,4′-dimethoxytrityl, 4-decyloxytrityl, 4-hexadecyloxytrityl, 9-(4-octadecyloxyphenyl)xanthene-9-yl, 1,1-bis-(4methoxyphenyl)-1′-pyrenylmethyl, p-phenylazophenyloxycarbonyl, 9-fluorenylmethoxycarbonyl, 2,4-dinitrophenylethoxycarbonyl, 4-(methylthiomethoxy)butyryl, 2-(methylthiomethoxymethyl)-benzoyl, 2-(isopropylthiomethoxymethyl)benzoyl, 2-(2,4-dinitrobenzenesulphenyloxymethyl)benzoyl, levulinyl, triethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, triphenylsilyl, benzoylformyl, acetyl, chloroacetyl, dichloroacetyl, trichloroacetyl, trifluoroacetyl, pivaloyl, benzoyl, p-phenylbenzoyl, or acetoacetyl.

18. A compound of claim 16 , wherein n is 2.

19. A compound of claim 16 , wherein SM is selected from a controlled pore glass, oxalyl-controlled pore glass, silica-containing particles, polymers of polystene, copolymers of polystyrene, and divinylbenzene, copolymers of dimethylacrylamide and N,N-bisacryloylethylenediamine, a soluble support medium, or PEPS.

20. A compound of claim 1 having the formula:

21. A compound of claim 20 wherein:

W is SM or L-SM;

Q is hydrogen, a blocking group, a protected or unprotected nucleosidyl moiety, a protected or unprotected nucleosidyl moiety attached through a phospholinker, or a protected or unprotected oligonucleotidyl moiety; and

A is a substituted or unsubstituted aromatic group.

22. A compound of claim 21 wherein Q is hydrogen.

23. A compound of claim 21 wherein A is phenyl.

24. A compound of claim 21 wherein Q is hydrogen, a protected or unprotected nucleosidyl moiety, a protected or unprotected nucleosidyl moiety attached through a phospholinker, or a protected or unprotected oligonucleotidyl moiety, and A is phenyl.

25. A process of making a compound of formula (II):

wherein:

A is independently selected from hydrogen, a blocking group, SM, L-SM, a substituted or unsubstituted, saturated, partially saturated or unsaturated aliphatic group, a substituted or substituted, saturated, partially saturated or unsaturated aliphatic ether, a substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, or a substituted or unsubstituted heterocyclic;

G 1 is independently selected in O, S, CR 1 R 2 , or NR 3 ;

each of R 1 and R 2 is independently selected from hydrogen, a substituted or unsubstituted, saturated, partially saturated or unsaturated aliphatic group, substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, or substituted or unsubstituted heterocyclic;

R 3 is independently selected from hydrogen, a blocking group, a saturated, partially saturated or unsaturated aliphatic group, substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, or substituted or unsubstituted heterocyclic;

each of R U , R V , R W , R X , R Y , and R Z is independently selected from hydrogen, substituted or unsubstituted allyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

each of Q and W is independently selected from hydrogen, a blocking group, SM, L-SM, a substituted or unsubstituted, a saturated, or partially saturated aliphatic group, a substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, a substituted or unsubstituted heterocyclic, a protected or unprotected nucleosidyl moiety, a protected or unprotected nucleosidyl moiety attached through a phospholinker, or a protected or unprotected oligonucleotidyl moiety;

SM is a support medium;

L is a bifunctional linking moiety; and

each of Y 1 and Y 2 is independently selected from O, S, NR 3 , or CR 1 R 2 ;

wherein at least one of A, Q, and W is SM or L-SM;

the process comprising,

providing a compound of formula (V):

and

reacting said compound of formula (VII) with a primary amine of formula (VIII): NH 2 -A, wherein A is as defined above.

26. A process for functionalizing a support medium with a first monomeric subunit, the process comprising:

providing a support-bound compound of formula (II):

wherein:

A is independently selected from hydrogen; a blocking group; SM; L-SM; a substituted or unsubstituted aliphatic group; a substituted or unsubstituted aliphatic ether; unsaturated a substituted or unsubstituted aromatic; substituted or unsubstituted heteroaromatic; or a substituted or unsubstituted heterocyclic;

SM is a support medium;

L is (C═O)—(CH 2 ) n —(C═O)O—, where n is an integer from 1 to 20;

G 1 is independently selected from O, S, CR 1 R 2 , or NR 3 ;

each of R 1 and R 2 is independently selected from hydrogen, a substituted or unsubstituted, saturated, partially saturated or unsaturated aliphatic group, substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, or substituted or unsubstituted heterocyclic;

R 3 is independently selected from hydrogen, a blocking group, substituted or unsubstituted aliphatic group, substituted or unsubstituted aromatic, substituted or unsubstituted heteroaromatic, or substituted or unsubstituted heterocyclic;

each of R U , R V , R W , R X , R Y , and R Z is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl;

one of Q or W is SM or L-SM, and the other of Q or W is a blocking group;

and

each of Y 1 and Y 2 is independently selected from O, S, NR 3 , or CR 1 R 2 ;

deblocking one of Q or W to give a reactive hydroxyl; and

treating said reactive hydroxyl with a first monomeric subunit having a further protected hydroxyl group to form a monomer-functionalized support medium.

27. The process of claim 26 , wherein the first monomeric subunit is an activated phosphoramidite nucleoside.

28. The process of claim 26 , further comprising reacting said monomer-functionalized support medium with a capping agent; and optionally treating said monomer-functionalized support medium with an oxidizing agent.

29. The process of claim 28 , further comprising:

(a) deblocking said further protected hydroxyl group to give a reactive hydroxyl;

(b) treating said reactive hydroxyl with an additional monomeric subunit bearing a further protected hydroxyl to produce an extended compound;

(c) reacting the extended compound with a capping reagent;

(d) optionally contacting the product of step (b) with an oxidizing or sulfurizing agent;

optionally repeating steps (a)–(d) one or more times to form an oligomeric compound.

30. The process of claim 29 , wherein said treating of said reactive hydroxyl group with a further monomeric subunit is performed in the presence of an activating agent.

31. The process of claim 26 , wherein said support medium is controlled pore glass, oxalyl-controlled pore glass, silica-containing particles, polymers of polystyrene, copolymers of polystyrene, copolymers of styrene and divinylbenzene, copolymers of dimethylacrylamide and N,N′-bisacryloylethylenediamine, soluble support medium or PEPS.

32. The process of claim 26 , wherein said support medium is controlled pore glass, polymers of polystyrene or copolymers of polystyrene.

33. The process of claim 26 , wherein said blocking group is 4,4′-dimethoxytrityl, monomethoxytrityl, 9-phenylxanthen-9-yl, 9-(p-methoxyphenyl) xanthen-9-yl, t-butyl, t-butoxymethyl, methoxymethyl, tetrahydropyranyl, 1-ethoxyethyl, 1-(2-chloroethoxy)ethyl, 2-trimethylsilylethyl, p-chlorophenyl, 2,4-chlorophenyl, benzyl, 2,6-dichlorobenzyl, diphenylmethyl, p,p-dinitrobenzhydryl, p-nitrobenzyl, triphenylmethyl, trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, triphenylsilyl, benzoylformate, acetyl, chloroacetyl, trichloroacetyl, trifluoroacetyl, pivaloyl, benzoyl, p-phenylbenzoyl, mesyl, tosyl, 4,4′,4″-tris-(benzyloxy)trityl, 4,4′,4″-tris-(4,5-dichlorophthalimido)trityl 4,4′,4″-tris(levulinyloxy)tityl, 3-(imidazolylmethyl)-4,4′-dimethoxytrityl, 4-decyloxytrityl, 4-hexadecyloxytrityl, 9-(4-octadecyloxyphenyl)xanthene-9-yl, 1,1-bis-(4-methoxyphenyl)-1-pyrenyl methyl, p-phenylazophenyloxycarbonyl, 9-fluorenylmethoxycarbonyl, 2,4-dinitrophenylethoxy carbonyl, 4-(methylthiomethoxy)butyryl, 2-(methylthiomethoxymethyl)-benzoyl, 2-(isopropylthiomethoxymethyl)benzoyl, 2-(2,4dinitrobenzenesulphenyloxymethyl)benzoyl, or levulinyl groups.

34. The process of claim 29 , wherein said oligomeric compound is an oligonucleotide, modified oligonucleotide, oligonucleotide analog, oligonucleotide, oligonucleotide mimetic, hemimer, gapmer or chimera.