Acid and base stable diphenylmethanol derivatives and methods of use

1. A compound of the formula:

wherein

each of R 1 , R 2 , R 3 , and R 4 is independently hydrogen, lower alkyl, or halide, provided at least one of R 1 , R 2 , R 3 , and R 4 is halide;

R 5 is hydrogen;

each of X 1 and X 2 is independently —OR 6 , —NR 7 R 8 , or —SR 9 ;

each R 6 is independently hydrogen, alkyl, carbonyl, or a hydroxy protecting group;

each R 7 is independently hydrogen or alkyl;

each R 8 is independently hydrogen, alkyl, or a nitrogen protecting group; and

each R 9 is independently hydrogen, alkyl, or a thiol protecting group.

2. The compound according to claim 1 , wherein at least two of R 1 , R 2 , R 3 , and R 4 are halides.

3. The compound according to claim 1 , wherein at least three of R 1 , R 2 , R 3 , and R 4 are halides.

4. The compound according to claim 1 , wherein R 1 , R 2 , R 3 , and R 4 are halides.

5. The compound according to claim 1 , wherein each halide is independently selected from the group consisting of Cl, Br, and I.

6. The compound according to claim 1 , wherein halide is Cl.

7. The compound according to claim 1 , wherein X 1 is —OR 6 , and R 6 is as defined in claim 1 .

8. The compound according to claim 7 , wherein R 6 is hydrogen or carbonyl.

9. The compound according to claim 1 , wherein X 2 is —OR 6 , and R 6 is as defined in claim 1 .

10. The compound according to claim 9 , wherein R 6 is alkyl.

11. A solid-substrate of the formula:

wherein

n is an integer from 1 to about 20;

each of R 1 , R 2 , R 3 , and R 4 is independently hydrogen, lower alkyl, or halide, provided at least one of R 1 , R 2 , R 3 , and R 4 is halide;

R 5 is hydrogen or alkyl;

X 1 is —OR 6 , —NR 7 R 8 , or —SR 9 ;

each of X 2 and Y 2 is independently —O—, —NR 8 —, or —S—;

R 6 is hydrogen, alkyl, carbonyl, or a hydroxy protecting group;

R 7 is hydrogen or alkyl;

each R 8 is independently hydrogen, alkyl, or a nitrogen protecting group;

R 9 is hydrogen, alkyl, or a thiol protecting group;

Y 1 is O, NR 10 , or S;

R 10 is hydrogen, alkyl, —OR 11 , or —NR 12 ;

R 11 and R 12 are hydrogen or alkyl; and

Z is a solid substrate.

12. The solid-substrate according to claim 11 , wherein R 1 , R 2 , R 3 , and R 4 are halides.

13. The solid-substrate according to claim 12 , wherein each halide is independently selected from the group consisting of Cl, Br, and I.

14. The solid-substrate according to claim 12 , wherein halide is Cl.

15. The solid-substrate according to claim 11 , wherein R 5 is hydrogen.

16. The solid-substrate according to claim 11 , wherein X 1 is —OR 6 , and R 6 is that defined in claim 11 .

17. The solid-substrate according to claim 16 , wherein R 6 is hydrogen or carbonyl.

18. The solid-substrate according to claim 11 , wherein X 2 is —O—.

19. The solid-substrate according to claim 11 , wherein Y 1 is O.

20. The solid-substrate according to claim 11 , wherein Y 2 is —NR 8 —, and R 8 is as defined in claim 11 .

21. A method of performing solid-phase synthesis comprising

(a) contacting a solid-substrate of the formula:

with a first reactive reagent comprising a first corresponding functional group chemically reactive with X 1 of the solid-substrate under conditions sufficient to react the corresponding functional group with X 1 , thus providing a solid-substrate bound product;

(b) optionally reacting the solid-substrate bound product and another reactive reagent comprising another corresponding functional group under conditions sufficient to produce a growing polymeric chain; and

(c) repeating said step (b) until a desired product is obtained,

wherein

n is an integer from 1 to about 20;

each of R 1 , R 2 , R 3 , and R 4 is independently hydrogen, lower alkyl, or halide, provided at least one of R 1 , R 2 , R 3 , and R 4 is halide;

R 5 is hydrogen or alkyl;

X 1 is —OH, —NHR 8 , or —SH;

each of X 2 and Y 2 is independently —O—, —NR 8 —, or —S—;

each R 8 is independently hydrogen, alkyl, or a nitrogen protecting group;

Y 1 is O, NR 10 , or S;

R 10 is hydrogen, alkyl, —OR 11 , or —NR 12 ;

R 11 and R 12 are hydrogen or alkyl; and

Z is a solid substrate.

22. The method of claim 21 , wherein the reactive reagent is selected from the group consisting of a nucleotide, saccharide, amino acid, and a derivative thereof.

23. The method of claim 21 , wherein Z is a bead, wafer, film, disc or plate.

24. The method of claim 23 , wherein Z comprises a material selected from organosilane-treated glass, organosilane-treated silicon, polypropylene, polyethylene, and polystyrene.

25. A method for producing a compound of the formula:

said method comprising:

contacting an acyl halide compound of the formula:

with an aromatic compound of the formula:

in the presence of a coupling catalyst under conditions sufficient to produce the compound of Formula IA,

wherein

each of R 1 , R 2 , R 3 , and R 4 is independently hydrogen, lower alkyl, or halide, provided at least one of R 1 , R 2 , R 3 , and R 4 is halide;

X is a CI

Y is O;

each of X 1 and X 2 is independently —OR 6 , —NR 7 R 8 , or —SR 9 ;

each R 6 is independently hydrogen, alkyl, carbonyl, or a hydroxy protecting group;

each R 7 is independently hydrogen or alkyl;

each R 8 is independently hydrogen, alkyl, or a nitrogen protecting group; and

each R 9 is independently hydrogen, alkyl, or a thiol protecting group.