Claims
- 1. A process for the production of a polyphenol oligomer, wherein said oligomer is comprised of monomeric units, each unit being comprised of a coupled polyphenol monomer, said process comprising the steps of:
(a) protecting each phenolic hydroxyl group of a first and a second polyphenol monomer with a protecting group to produce a first and second protected polyphenol monomer independently selected from monomers represented by the formula: 44c is an integer from 1 to 3; d is an integer from 1 to 4; e is an integer from 0 to 2; f is an integer from 0 to 2; R1 is H, OH or OR3; R and R3 are independently protecting groups; and R2 is halo; (b) functionalizing the 4-position of the first protected polyphenol monomer to produce a functionalized protected polyphenol monomer having the formula: 45 wherein
c is an integer from 1 to 3; d is an integer from 1 to 4; e is an integer from 0 to 2; f is an integer from 0 to 2; y is an integer from 2 to 6; R1 is H, OH or OR3; R4 is H or R5; R, R3 and R5 are independently protecting groups; and R2 is halo; (c) coupling the second protected polyphenol monomer with the functionalized protected polyphenol monomer to produce a protected polyphenol dimer as the polyphenol oligomer; and (d) optionally repeating the functionalization and coupling steps to form the polyphenol oligomer having n monomeric units, wherein n is an integer from 3 to 18.
- 2. The process according to claim 1, wherein at least one R2 is halo in at least one of the protected polyphenol monomers.
- 3. The process according to claim 1, wherein at least one R2 is halo for said second protected polyphenol monomer.
- 4. The process according to claim 1, wherein R1 is OR3 or R4 is R5 in the functionalized protected polyphenol monomer.
- 5. The process according to claim 4, wherein R3 is an alkyl silyl protecting group.
- 6. The process according to claim 2, wherein halo is bromo.
- 7. The process according to claim 6, wherein said protected polyphenol monomer is a brominated protected epicatechin or brominated protected catechin.
- 8. The process according to claim 7, wherein said epicatechin is an 8-bromoepicatechin or an 8-bromocatechin.
- 9. The process according to claim 7, wherein said epicatechin is a 6,8,6′-tribromo-epicatechin or a 6,8,6′-tribromo-catechin.
- 10. The process according to claim 2, wherein at least one R2 is halo for said functionalized protected polyphenol monomer.
- 11. The process according to claim 10, wherein said functionalizing and coupling steps are repeated to form a halogenated polyphenol oligomer having 3 to 18 monomeric units.
- 12. The process according to claim 10, wherein halo is bromo.
- 13. The process according to claim 12, wherein said brominated functionalized polyphenol monomer is a brominated functionalized epicatechin or a brominated functionalized catechin.
- 14. The process according to claim 13, wherein said epicatechin is an 8-bromoepicatechin or an 8-bromocatechin.
- 15. The process according to claim 13, wherein said epicatechin is a 6,8,6′-tribromo-epicatechin or a 6,8,6′-tribromo-catechin.
- 16. The process according to claim 1, wherein n is an integer from 5 to 12.
- 17. The process according to claim 1, further comprising halogenating the polyphenol oligomer.
- 18. The process according to claim 1, wherein the step of functionalizing the 4-position of the protected polyphenol monomer comprises oxidatively -functionalizing the 4-position of the protected polyphenol monomer using a quinone oxidizing agent in the presence of a diol.
- 19. The process according to claim 18, wherein the diol is ethylene glycol and y is 2.
- 20. The process according to claim 1, wherein R is independently C1-C4 alkyl, benzyl, substituted benzyl, a silyl moiety containing C1-C6 alkyl or aryl substituents, and, when c or d is 2 and are adjacent, methylene, diphenylmethylene or substituted diphenylmethylene, wherein said substituted benzyl or each substituted phenyl may contain substituents selected from the group consisting of halo, nitro, cyano, aryl, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy C1-C6 haloalkoxy, C3-C8 cycloalkyl, C3-C8 cycloalkoxy.
- 21. The process according to claim 1, further comprising removing the protecting group from the phenolic hydroxyl groups of the polyphenol oligomer to produce an unprotected polyphenol oligomer.
- 22. The process according to claim 1, wherein the R is benzyl.
- 23. The process according to any of claims 1 and 21, further comprising the step of forming a derivative of the polyphenol oligomer by esterifying the polyphenol oligomer at the 3-position of at least one monomeric unit, to produce an esterified polyphenol oligomer.
- 24. The process according to any of claims 1 and 21, further comprising the step of forming a derivative of the polyphenol oligomer by glycosylating the polyphenol oligomer at the 3-position of at least one monomeric unit, to produce a glycosylated polyphenol oligomer.
- 25. The process according to claim 23, wherein the 3-position of at least one monomeric unit is converted to a derivative group selected from the group consisting of —OC(O)aryl, —OC(O)-substituted aryl, —OC(O)-styryl, and —OC(O)-substituted styryl; wherein said substituted aryl or substituted styryl contains at least one substituent selected from the group consisting of halo, hydroxyl, nitro, cyano, amino, thiol, methylenedioxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C3-C8 cycloalkyl, and C3-C8 cycloalkoxy.
- 26. The process according to claim 23, wherein the 3-position of at least one monomeric unit is converted to a derivative group derived from an acid selected from the group consisting of caffeic, cinnamic, coumaric, ferulic, gallic, hydroxybenzoic and sinapic acids.
- 27. The process according to claim 24, wherein the 3-position of at least one monomeric unit is converted to a derivative group selected from the group consisting of —O-glycoside or an —O-substituted glycoside, wherein the substituted glycoside is substituted by —C(O)aryl, —C(O)-substituted aryl, —C(O)-styryl, or —C(O)-substituted styryl; wherein said substituted aryl or substituted styryl may contain the substituents selected from the group consisting of halo, hydroxyl, nitro, cyano, amino, thiol, methylenedioxy, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C3-C8 cycloalkyl, and C3-C8 cycloalkoxy.
- 28. The process according to claim 27, wherein the glycoside is selected from the group consisting of glucose, galactose, xylose, rhamnose and arabinose.
- 29. The process according to any of claims 1 and 21, providing the polyphenol oligomer having the formula:
- 30. A compound of the formula:
- 31. A compound of the formula:
- 32. A process for the production of a polymeric compound of the formula A, wherein A is a monomer of the formula:
- 33. The process according to claim 32, wherein n is 5.
- 34. The process according to claim 32, wherein the sugar is selected from the group consisting of glucose, galactose, xylose, rhamnose and arabinose.
- 35. The process according to claim 32, wherein the phenolic moiety is selected from the group consisting of caffeic, cinnamic, coumaric, ferulic, gallic, hydroxybenzoic and sinapic acids.
- 36. A pharmaceutical composition comprising a compound of the formula:
- 37. A method for treating a subject in need of treatment with an anticancer agent comprising administering an effective amount to the subject a composition as claimed in claim 36.
- 38. The method of claim 37, wherein said cancer is breast cancer.
- 39. A pharmaceutical composition comprising a compound of the formula:
- 40. A method for treating a subject in need of treatment with an anticancer agent comprising administering an effective amount to the subject a composition as claimed in claim 39.
- 41. The method of claim 40, wherein said cancer is breast cancer.
BACKGROUND OF THE INVENTION
[0001] This application is a continuation-in part of U.S. patent application Ser. No. 08/948,226, filed Oct. 9, 1997.
Continuations (1)
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Number |
Date |
Country |
Parent |
09169554 |
Oct 1998 |
US |
Child |
10017812 |
Dec 2001 |
US |
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
08948226 |
Oct 1997 |
US |
Child |
09169554 |
Oct 1998 |
US |