Claims
- 1. Process for the production of cyproterone acetate (M), comprising
(a) Converting 6,7α-oxido-4-pregnene-17α-ol-3,20-dione-17-acetate (J2) into chlormadinone acetate (K2) by a single step procedure; (b) Introducing a double bond at position 1 of (K2) to yield delmadinone acetate (L2); and (c) Introducing a methylene group bridging positions 1 and 2 of (L2) to yield cyproterone acetate (M).
- 2. Process according to claim 1, wherein 6,7α-oxido-4-pregnene-17α-ol-3,20-dione-17-acetate (J2) is produced by a process comprising
(d) Introducing a double bond at position 6 of 17α-acetoxyprogesterone (H) to convert it into 4,6-pregnadiene-17α-ol-3,20-dione-17-acetate (12); (e) Converting the double bond at position 6 of (12) into an epoxy function to yield 6,7α-oxido-4-pregnene-17α-ol-3,20-dione-17-acetate (J2).
- 3. Process according to claim 2, wherein step (d) is carried out using chloranil.
- 4. Process according to claim 2, wherein step (e) is carried out using m-perbenzoic acid or monoperoxyphthalic acid.
- 5. Process according to claim 2, wherein 17α-acetoxyprogesterone (H) is produced by a process comprising converting solasodine (A) into 17α-acetoxyprogesterone (H) by means known in the art.
- 6. Process according to claim 2, wherein 16-dehydropregnenolone acetate (B) is converted into 16,17-epoxy-pregnenolone (C) by a single step procedure.
- 7. Process according to claim 6, wherein the conversion of (B) to (C) is achieved using hydrogen peroxide in alkaline solution.
- 8. Process for the production of cyproterone acetate (M), comprising
(f) Introducing two double bonds at positions 1 and 6 of 17α-acetoxyprogesterone (H) to convert it into the 1,4,6-triene compound (I1) by a single step procedure; (g) Introducing methylene group bridging positions 1 and 2 to yield the 1,2α-methylene compound (J1); (h) Introducing an oxido group bridging positions 6 and 7 of (J1) to yield the 6,7α-epoxy compound (K1); (i) Transforming the epoxy group of (K1) to the 6-chloro-7-hydroxy compound (L1); and (j) Converting (L1) to cyproterone acetate (M).
- 9. Process according to claim 8, wherein DDQ is used in step (f).
- 10. Process according to claim 8, wherein TMSI and an alkali hydride are used in step (g).
- 11. Process according to claim 8, wherein trifluoromethyl sulfonyl chloride and lithium chloride are used in step (i).
- 12. Process according to claim 1, wherein step (a) is carried out by passing anhydrous hydrogen chloride gas through a reaction mixture containing 6,7α-oxido-4-pregnene-17α-ol-3,20-dione-17-acetate (J2).
- 13. Process according to claim 1, wherein step (b) is carried out by the use of 2,3-dichloro-5,6-dicyano-benzoquinone (DDQ).
- 14. Process according to claim 1, wherein step (c) is carried out using trimethyl sulfoxonium iodide (TMSI) and an alkali hydride, preferably sodium hydride.
- 15. Process for the production of cyproterone actetate (M), comprising reacting delmadinone acetate (L2) with TMSI and an alkali hydride.
- 16. Process of claim 15, wherein said alkali hydride is sodium hydride.
- 17. Process for the production of cyproterone actetate (M), comprising reacting compound (K1) of formula
- 18. Process for the production of 16-dehydropregnenolone actetate (B), comprising
(k) Acetylating solasodine (A) to give O,N-diacetylsolasodine; (l) Isomerising O,N-diacetylsolasodine to give pseudosolasodine diacetate; (m) Oxidising the resulting pseudosolasodine diacetate in the presence of a phase transfer catalyst.
- 19. The process of claim 18, wherein the phase transfer catalyst is tetrabutylammonium hydrogen sulfate.
- 20. The process of claim 18, wherein the oxidising agent is potassium dichromate, or sodium dichromate.
- 21. Process of production of delmadinone acetate (L2) comprising adding chlormadinone acetate (K2) to a culture of a microorganism capable of converting (K2) into (L2), and isolating the resulting delmadinone actetate from the culture.
- 22. The process of claim 21, wherein the microorganism is Arthrobacter simplex or Bacillus sphaericus.
- 23. The process of claim 21, wherein said Arthrobacter simplex is, ATCC 6946, or Bacillus sphaericus, ATCC 13805.
- 24. The process of claim 21, wherein an electron carrier is added to the culture, preferably menadione (2-methyl-1,4-naphthoquinone).
- 25. The process of claim 24, wherein said electron carrier is 2-methyl-1,4-naphthoquinone.
- 26. The process of claim 21, wherein a steroid is added to the culture.
- 27. The process of claim 26, wherein said steroid is hydrocortisone.
- 28. The process of claim 21, wherein a surfactant is added to the culture.
- 29. The process of claim 21, wherein said surfactant is polyoxyethylenesorbitan monooleate.
Priority Claims (1)
Number |
Date |
Country |
Kind |
02009663 |
Apr 2002 |
EP |
|
RELATED APPLICATIONS
[0001] Benefit of U.S. Provisional Application Serial No. 60/383,305, filed on May 23, 2002 is hereby claimed, and said Application is herein incorporated by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60383305 |
May 2002 |
US |