Synthesis of oligo/poly(catechins) and methods of use

1. A polymer comprising at least two repeat units independently selected from the group consisting of:

or a pharmaceutically acceptable salt thereof;

wherein:

each repeat unit is independently optionally substituted with one or more substituents;

between one and four —H atoms in each repeat unit attached to the oxygen or carbon at each * are independently replaced by a polymer link; and

each n is independently an integer from 0 to 170 inclusive, wherein the sum of all ns is an integer from 2 to 170 inclusive, and

wherein the polymer is formed by polymerizing the repeat unit in the presence of an oxido-reductase, hydrogen peroxide, and a polymerization solubilizer that includes ethanol and water.

2. The polymer of claim 1 , wherein the sum of all ns is an integer from 10 to 170 inclusive.

3. The polymer of claim 2 , wherein the polymer is a copolymer.

4. The polymer of claim 3 , wherein the repeat units are:

or a pharmaceutically acceptable salt thereof;

wherein:

each repeat unit is independently optionally substituted with one or more substituents.

5. The polymer of claim 3 , wherein the repeat units are:

or a pharmaceutically acceptable salt thereof;

wherein:

each repeat unit is independently optionally substituted with one or more substituents.

6. The polymer of claim 3 , wherein the repeat units are:

or a pharmaceutically acceptable salt thereof;

wherein:

each repeat unit is independently optionally substituted with one or more substituents.

7. The polymer of claim 3 , wherein the copolymer further comprises the repeat unit:

or a pharmaceutically acceptable salt thereof;

wherein:

each repeat unit is independently optionally substituted with one or more substituents.

8. The polymer of claim 7 , wherein the repeat units are:

or a pharmaceutically acceptable salt thereof;

wherein:

each repeat unit is independently optionally substituted with one or more substituents.

9. The polymer of claim 7 , wherein the repeat units are:

or a pharmaceutically acceptable salt thereof;

wherein:

each repeat unit is independently optionally substituted with one or more substituents.

10. The polymer of claim 2 , wherein each repeat unit is represented by the following structural formula:

or a pharmaceutically acceptable salt thereof, wherein each repeat unit is independently optionally substituted with one or more substituents.

11. The polymer of claim 10 , wherein each repeat unit is independently selected from the group consisting of:

or a pharmaceutically acceptable salt thereof, wherein each repeat unit is independently optionally substituted with one or more substituents.

12. The polymer of claim 2 , having a UV-visible spectrum including a peak between 350 and 450 nm.

13. The polymer of claim 2 , wherein the polymer has a solubility in 1 mL of water of between 0.5 and 5 mg at room temperature.

14. The polymer of claim 13 , wherein the polymer has a solubility in 1 mL of water of between 1 and 3 mg at room temperature.

15. The polymer of claim 2 , wherein the polymer has an average molecular weight of between 3,000 and 50,000 Daltons.

16. The polymer of claim 15 , wherein the polymer has an average molecular weight of between 10,000 and 50,000 Daltons.

17. The polymer of claim 2 , wherein a majority of the repeat units are the same enantiomer, whereby the polymer is chiral.

18. The polymer of claim 17 , wherein substantially all the repeat units of the polymer are the same enantiomer, whereby the oligo/polyflavanoid is chiral.

19. The polymer of claim 18 , wherein all the repeat units of the polymer are the same enantiomer, whereby the oligo/polyflavanoid is chiral.

20. The polymer of claim 2 , wherein one or more repeat units are substituted with one or more substituents independently selected from —F, —Cl, —Br, —I, —CN, —NO 2 , —OR a , —C(O)R a , —OC(O)R a , —C(O)OR a , —SR a , —C(S)R a , —OC(S)R a , —C(S)OR a , —C(O)SR a , —C(S)SR a , —S(O)R a , —SO 2 R a , —SO 3 R a , —PO 2 R a R b , —PO 3 R a R b , —N(R a R b ), —C(O)N(R a R b ), —C(O)NR a NR b SO 2 R c , —C(O)NR a SO 2 R c , —C(O)NR a CN, —SO 2 N(R a R b ), —SO 2 N(R a R b ), —NR c C(O)R a , —NR c C(O)OR a , —NR c C(O)N(R a R b ), —C(NR c )—N(R a R b ), —NR d —C(NR c )—N(R a R b ), —NR a N(R a R b ), —CR c ═CR a R b , —C≡CR a , ═O, ═S, ═CR a R b , ═NR a , ═NOR a , ═NNR a , optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aliphatic, optionally substituted cycloaliphatic, optionally substituted heterocyclic, optionally substituted benzyl, optionally substituted aryl, and optionally substituted heteroaryl; wherein R a -R d are each independently —H or an optionally substituted aliphatic, optionally substituted cycloaliphatic, optionally substituted heterocyclic, optionally substituted benzyl, optionally substituted aryl, or optionally substituted heteroaryl, or, —N(R a R b ), taken together, is an optionally substituted heterocyclic group.

21. The polymer of claim 2 , wherein one or more repeat units are unsubstituted.

22. The polymer of claim 21 , wherein all repeat units are unsubstituted.

23. A biocompatible composition comprising a biocompatible solvent and an oligo/polyflavanoid or a pharmaceutically acceptable salt, solvate, or complex thereof wherein the oligo/polyflavanoid is formed by polymerizing a repeat unit in the presence of an oxido-reductase, hydrogen peroxide, and a polymerization solubilizer that includes ethanol and water.

24. The biocompatible composition of claim 23 , wherein the oligo/polyflavanoid comprises repeat units selected from the group consisting of optionally substituted catechin, quercitin, flavonone, isoflavone, chalcone, anthocyanidin, chrysin, primuletin, fisetin, naringin, hesperidin, prunin, daidzein, genistein, pelargonidin, cyanidin and delphinidin.

25. The biocompatible composition of claim 24 , wherein the oligo/polyflavanoid is selected from oligo/poly(−)-catechin, oligo/poly(−)-epicatechin, oligo/poly(−)-gallocatechin, oligo/poly(−)-catechin gallate, oligo/poly(−)-epigallocatechin, oligo/poly(−)-gallocatechin gallate, oligo/poly(−)-epicatechin gallate, oligo/poly(−)-epigallocatechin gallate, oligo/poly(+)-catechin, oligo/poly(+)-epicatechin, oligo/poly(+)-gallocatechin, oligo/poly(+)-catechin gallate, oligo/poly(+)-epigallocatechin, oligo/poly(+)-gallocatechin gallate, oligo/poly(+)-epicatechin gallate, and oligo/poly(+)-epigallocatechin gallate.

26. The biocompatible composition of claim 25 , wherein the oligo/polyflavanoid is oligo/poly(−)-catechin or oligo/poly(+)-catechin.

27. The biocompatible composition of claim 25 , wherein the oligo/polyflavanoid is oligo/poly(−)-epicatechin or oligo/poly(+)-epicatechin.

28. The biocompatible composition of claim 25 , wherein the oligo/polyflavanoid is oligo/poly(−)-epicatechin.

29. The biocompatible composition of claim 25 , wherein the oligo/polyflavanoid is complexed with an amphiphile.

30. The biocompatible composition of claim 29 , wherein the amphiphile is selected from the group consisting of polyethylene oxide, sulfonated polystyrene, poly (vinyl phosphonic acid) sodium dodecyl benzenesulfonate, polyoxyethylene(10), isooctylphenyl ether (Triton X-100), p-toluenesulphonic acid monohydrate, deoxyribonucleic acid, ribonucleic acid, 1-palmitoly-2-oleoyl-sn-glycerol-3-phosphate, sodium octylsulfonate, 1-palmitoly-2-oleoyl-sn-glycero-3-phosphocholine, and benzoyl-L-tyrosine-p-nitroanilde.

31. The biocompatible composition of claim 29 , wherein the amphiphile is biocompatible.

32. The biocompatible composition of claim 31 , wherein the amphiphile is selected from the group consisting of polyethylene oxide, sulfonated polystyrene, poly (vinyl phosphonic acid), polyoxyethylene(10), deoxyribonucleic acid and ribonucleic acid.

33. The biocompatible composition of claim 32 , wherein the amphiphile is polyethylene oxide.

34. A method of synthesizing a polymer comprising at least two repeat units independently selected from the group consisting of:

or a pharmaceutically acceptable salt thereof;

wherein:

each repeat unit is independently optionally substituted with one or more substituents;

between one and four —H atoms in each repeat unit attached to the oxygen or carbon at each * are independently replaced by a polymer link; and

each n is independently an integer from 0 to 170 inclusive, wherein the sum of all ns is an integer from 2 to 170 inclusive;

comprising polymerizing the repeat unit in the presence of an oxido-reductase, hydrogen peroxide, and a polymerization solubilizer that includes ethanol and water.

35. A method of treating breast cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a polymer of claim 1 .

36. A method of or treating colon cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a polymer of claim 1 .