Claims
- 1. A compound of the structural formula
- 2. A compound of the structural formula
- 3. A method of making palmarumycin CP,, said method comprising:
adding pyridinium p-toluenesulfonate to a solution of 5-hydroxy-8-methoxy- I - tetralone and ethylene glycol in benzene and heating at reflux for 30 hours in a flask equipped with a Dean-Stark apparatus to produce 5-hydroxy-g-methoxy-1 ,2,3 ,4-tetrahydronaphthalene-l1-spiro-2 ′- dioxolane; adding K2C03 and CU20 to a solution of 5-hydroxy-8-methoxy-1,2,3,4- tetrahydronaphthalene-l1-spiro-2′-dioxolane and 8-iodo-l1-methoxynaphthalene, adding additional Cu20, treating with TsOH in a mixture of acetone/water to produce 8-methoxy-5-(8′- methoxynaphthalene-1 ′-yloxy)-3 ,4-dihydro-2H-naphthalen- 1 -one; adding BBr3 in dichoromethane to 8-methoxy-5-(8′-methoxynaphthalene-1′- yloxy)-3,4-dihydro-2H-naphthalen-l-one to yield 8-hydroxy-5-(8′-hydroxynaphthalen-1′-yloxy)- 3,4-dihydro-2H-naphthalen-1 -one; reducing 8-hydroxy-5 -(8′-hydroxynaphthalen- 1 ′-yloxy)-3,4-dihydro-2H- naphthalen-l -one with lithium aluminum hydride adding trifluoroethanol and Phl(OAc)2 to produce (-8-hydroxy-1 -oxo-1 ,4,5,6,7,8-hexahydronaphthalene-4-spiro-2′-naphtho[l “,8”-de] [1′,3′]dioxin; and adding Dess-Martin periodinane to ()-8-hydroxy-1-oxo-1,4,5,6,7,8- hexahydronaphthalene-4-spiro-2′-naphtho[l “,8”-de][1′,3′]dioxin in dichloromethane and treating with MnO2 in dichloromethane to produce palmarumycin CP,.
- 4. A method of making deoxypreussomerin A, said method comprising:
adding pyridinium p-toluenesulfonate to a solution of 5-hydroxy-8-methoxy-I - tetralone and ethylene glycol in benzene and heating at reflux for 30 hours in a flask equipped with a Dean-Stark apparatus to produce 5-hydroxy-8-methoxy- 1,2,3,4-tetrahydronaphthalene-1 -spiro-2′- dioxolane; adding K2CO3 and Cu20 to a solution of 5-hydroxy-8-methoxy-1,2,3,4- tetrahydronaphthalene-l -spiro-2′-dioxolane and 8-iodo-1 -methoxynaphthalene, adding additional Cu20, treating with TsOH in a mixture of acetone/water to produce 8-methoxy-5-(8′- methoxynaphthalene-l ′-yloxy)-3,4-dihydro-2H-naphthalen-l-one; adding BBr3 in dichoromethane to 8-methoxy-5-(8′-methoxynaphthalene-l′- yloxy)-3,4-dihydro-2H-naphthalen-l-one to yield 8-hydroxy-5-(8′-hydroxynaphthalen-1′-yloxy)- 3,4-dihydro-2H-naphthalen-l -one; reducing 8-hydroxy-5-(8′-hydroxynaphthalen-1′-yloxy)-3,4-dihydro-2H- naphthalen-l-one with lithium aluminum hydride adding trifluoroethanol and Phl(OAc)2 to produce (i)-8-hydroxy-1 -oxo-1 ,4,5,6,7,8-hexahydronaphthalene-4-spiro-2′-naphtho[l “,8 ”-de] [1′,3 ]dioxin; adding cumene hydroperoxide and NaH to (I)-8-hydroxy-1 -oxo-1,4,5,6,7,8- hexahydronaphthalene-4-spiro-2′-naphtho[1“,8”-de][1′,3′]dioxin in TUF to produce an epoxide; and adding Dess-Martin periodinane to said epoxide in dichloromethane, treating with MnO2 in dry dichloromethane to yield deoxypreussomerin A.
- 5. A method of making a palmarumycin CPI analog comprising;
reacting palmarymycin CP, with an alcohol of the formula R-CH20H in the presence of diethyl azodicarboxylate and dichloromethane, wherein R is a member selected from the group consisting of (E)-HC=CHPh, (E)-HC=CHMe, n-C5H,I, (E)-CH2HC=CHEt, (m)-MeOPh, benzonitrile, 2-furyl, (E,E)-HC=C(Me)CH2CH2CH=CMe2, 3 -firyl, 2-pyridyl, 3 -pyridyl, 4-pyridyl, and HC=CH2.
- 6. A method of making a palmarumycin CPI analog comprising;
reacting palmarymycin CPI with an alcohol of the formula R-CH20H in the presence of diethyl azodicarboxylate and dichloromethane, wherein R is a member selected from the group consisting of (p)-MeOPh, C(Me)=CH2, C=ICH, p)-BrPh, (p)-CIPh, 2-furyl(5-(p)-BrPh), 2- furyl(5-(o)-ClPh), 2-furyl(5-(m)-ClPh), 2-furyl(5-(o)-CF3Ph), 2-faryl(5-(m)-CF3Ph), HC=CMe2, (E)-C(Me)=CHMe, and (Z)C(Me)=CHMe.
- 7. A method of inhibiting mitosis comprising exposing cells to a compound of the structural formula
- 8. The method of claim 7, wherein said cells comprise human cancer cells.
- 9. The method of claim 8, wherein said human cancer cells comprise breast cancer cells.
- 10. The method of claim 9, wherein said breast cancer cells comprise MCF-7 cells,
- 11. The method of claim 9, wherein said breast cancer cells comprise MDA-MB-23 1 cells.
- 12. The method of claim 8, wherein said human cancer cells comprise ovarian cancer cells.
- 13. The method of claim 12, wherein said ovarian cancer cells are a member selected from the group consisting of lA9, lA9/PTXIO and IA9/PTX22 cells.
- 14. A method of inhibiting mitosis comprising exposing cells to a compound of the structural formula
- 15. The method of claim 14, wherein said cells comprise human cancer cells.
- 16. The method of claim 15, wherein said human cancer cells comprise breast cancer cells.
- 17. The method of claim 16, wherein said breast cancer cells comprise MCF-7 cells.
- 18. The method of claim 16, wherein said breast cancer cells comprise MDA-MB-23 1 cells.
- 19. The method of claim 15, wherein said human cancer cells comprise ovarian cancer cells.
- 20. The method of claim 19, wherein said ovarian cancer cells are a member selected from the group consisting of IA9, lA9/PTXlO and 1A9/PTX22 cells.
- 21. A method of inhibiting proliferation of cells comprising exposing said cells to a compound of the structural formula
- 22. The method of claim 21, wherein said cells comprise human cancer cells.
- 23. The method of claim 22, wherein said human cancer cells comprise breast cancer cells.
- 24. The method of claim 23, wherein said breast cancer cells comprise MCF-7 cells.
- 25. The method of claim 23, wherein said breast cancer cells comprise MDA-MB-231 cells.
- 26. The method of claim 22, wherein said human cancer cells comprise ovarian cancer cells.
- 27. The method of claim 26, wherein said ovarian cancer cells are a member selected from the group consisting of 1 A9, I A9/PTX 10 and I A9/PTX22 cells.
- 28. A method of inhibiting proliferation of cells comprising exposing said cells to a compound of the structural formula
- 29. The method of claim 28, wherein said cells comprise human cancer cells.
- 30. The method of claim 29, wherein said human cancer cells comprise breast cancer cells.
- 31. The method of claim 30, wherein said breast cancer cells comprise MCF-7 cells.
- 32. The method of claim 30, wherein said breast cancer cells comprise MDA-MB-231 cells.
- 33. The method of claim 29, wherein said human cancer cells comprise ovarian cancer cells.
- 34. The method of claim 33, wherein said ovarian cancer cells are a member selected from the group consisting of IA9, IA9/PTXIO and 1A9/PTX22 cells.
- 35. A method of inhibiting a cell′s thioredoxin -thioredoxin reductase system comprising exposing cells to a compound of the structural formula
- 36. A method of inhibiting a cell's thioredoxin -thioredoxin reductase system comprising exposing said cells to a compound of the structural formula
- 37. A method of inhibiting a cell's thioredoxin - thioredoxin reductase system comprising exposing said cells to a compound of the structural formula
SYNTHESES AND METHODS OF USE OF NEW ANTIMITOTIC AGENTS
[0001] This application claims the benefit of U.S. Provisional Application No. 60/219,282 filed Jul. 19, 2000.
[0002] Statement Re2arding Federally-Sponsored Research This invention was supported by the United States Government under Grant No. CA-78039 awarded by the National Institutes of Health. The Government may have certain rights in the invention.
Provisional Applications (1)
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Number |
Date |
Country |
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60219282 |
Jul 2000 |
US |