Methods for the preparation, isolation and purification of epothilone B, and X-ray crystal structures of epothilone B
View Patent ↗The present invention relates to improved methods for the production, isolation and purification of epothilone B. These methods include, for example, a fermentation process for the production of epothilone B, isolation via adsorption onto a resin, and subsequent purification.
1. A crystalline solvate comprising: a toluene-containing epothilone B clathrate.
2. The crystalline solvate according to claim 1 characterized by unit cell parameters approximately equal to the following:
Cell dimensions:
a = 11.853(1) Å
b = 10.613(2) Å
c = 14.328(2) Å
Volume = 1659(1) Å 3
Space group
P2 1
Molecules/unit cell
4
Density (calculated) (g/cm 3 )
1.201
wherein the crystalline solvate is at a temperature of about −33° C.
3. The crystalline solvate according to claim 1 wherein said crystalline solvate is characterized by peaks in a powder x-diffraction pattern at a value of two theta (CuKα λ=1.5418 Å) of about 13.4, 20.2, 22.0, and 24.9, at a temperature of 23° C.
4. The crystalline solvate according to claim 3 wherein said crystalline solvate is further characterized by peaks in a powder x-ray diffraction pattern at a value of two theta (CuKα λ=1.5418 Å)of about 6.7, 8.2, 11.7, 12.7, 15.0, 15.8, 16.7, 18.5, 20.9, 21.5, 24.3, 26.3, 28.5, and 30.1, at a temperature of 23° C.
5. The crystalline solvate according to claim 1 , which comprises about one molecule of toluene per one molecule of the epothilone B.
6. The crystalline solvate according to claim 5 characterized by unit cell parameters approximately equal to the following:
Cell dimensions:
a = 11.853(1) Å
b = 10.613(2) Å
c = 14.328(2) Å
Volume = 1659(1) Å 3
Space group
P2 1
Molecules/unit cell
4
Density (calculated) (g/cm 3 )
1.201
wherein the crystalline solvate is at a temperature of about −33° C.
7. The crystalline solvate according to claim 5 wherein said crystalline solvate is characterized by peaks in a powder x-diffraction pattern at a value of two theta (CuKα λ=1.5418 Å) of about 13.4, 20.2, 22.0, and 24.9, at a temperature of 23° C.
8. The crystalline solvate according to claim 7 wherein said crystalline solvate is further characterized by peaks in a powder x-ray diffraction pattern at a value of two theta (CuKα λ=1.5418 Å) of about 6.7, 8.2, 11.7, 12.7,15.0, 15.8, 16.7, 18.5, 20.9, 21.5, 24.3, 26.3, 28.5, and 30.1, at a temperature of 23° C.
9. The crystalline solvate according to claim 1 characterized by: fractional atomic coordinates substantially as listed in Table 5.