Claims
- 1. A 5.beta.-.DELTA..sup.9(11) -steroid of the formula:
- where
- R.sub.6 is hydrogen, fluorine or chlorine atom or methyl group;
- R.sub.16.alpha. is a hydrogen, fluorine or chlorine atom or methyl group;
- R.sub.16.beta. is a hydrogen atom or methyl group with the proviso that one of R.sub.16.alpha. or R.sub.16.beta. is a hydrogen atom;
- R.sub.17 is alkyl of 1 through 6 carbon atoms, phenyl, p-methylphenyl, p-carboxyphenyl or p-carboalkoxyphenyl;
- R.sub.21 is a hydrogen, fluorine, chlorine or bromine atom or a --OR.sub.21a or --OSO.sub.2 CH.sub.3 group;
- R.sub.21a is a hydrogen atom, --COR.sub.21b or --PO(OH).sub.2 and pharmaceutically acceptable salts thereof;
- R.sub.21b is alkyl of 1 thru 6 carbon atoms, phenyl, p-methylphenyl, or p-carboxyphenyl, p-carboalkoxyphenyl, --CH.sub.2 CH.sub.2 COOH and pharmaceutically acceptable salts thereof; and
- .about. indicates the attached group can be in either the .alpha. or .beta. configuration.
- 2. A 5.alpha.-.DELTA..sup.9(11) -21-hydroxy-steroid of the formula ##STR2## where R.sub.6, R.sub.16.alpha., R.sub.16.beta., R.sub.17 and .about. are defined in claim 1.
- 3. A compound according to claim 2 where R.sub.2 and R.sub.7 are hydrogen atoms and R.sub.16.beta. is methyl.
- 4. A compound according to claim 2 where R.sub.2 and R.sub.7 are a hydrogen atom and R.sub.16.alpha. is methyl.
- 5. A compound according to claim 2 where R.sub.2, R.sub.7, R.sub.16.alpha. and R.sub.16.beta. are hydrogen atoms.
- 6. 17.alpha.,21-Dihydroxy-16.beta.-methyl-5.alpha.-pregn-9(11)-ene-3,20-dione 17-propionate 21-mesylate.
- 7. A process for preparing a 5.beta.-.DELTA..sup.9(11) -steroid of the formula: ##STR3## which comprises (1) hydrogenating a compound of the formula: ##STR4## in the presence of a hydrogenating catalyst selected from the group consisting of palladium on carbon, platinum on carbon, platinum dioxide, pallodium on barium carbonate, polladium on calcium carbonate, rhodium on alumina, rhodium on carbon, polladium on barium sulfate, polladium on zinc oxide, tris(triphenylphosphine)rhodium (I) chloride,
- (2) separating the 5.beta.-isomer from the 5.alpha.-isomer where R.sub.6, R.sub.16.alpha., R.sub.16.beta., R.sub.17, R.sub.21, and .about., are defined in claim 1 and where . . . is a single or double bond.
- 8. A process according to claim 7 where R.sub.6 is a hydrogen or fluorine atom or methyl group.
- 9. A process according to claim 8 where R.sub.6 is a hydrogen atom.
- 10. A process according to claim 7 where R.sub.16.alpha. is a hydrogen atom or methyl group.
- 11. A process according to claim 7 where R.sub.16.beta. is a hydrogen atom or methyl group.
- 12. A process according to claim 7 where R.sub.17 is alkyl of 1 thru 5 carbon atoms, phenyl, or paramethylphenyl.
- 13. A process according to claim 12 where R.sub.17 is alkyl of 1 thru 4 carbon atoms or phenyl.
- 14. A process according to claim 7 where R.sub.21 is a hydrogen, fluorine, or chlorine atom or a --OR.sub.21a group where R.sub.21a is defined in claim 1.
- 15. A process according to claim 14 where R.sub.21 is a hydrogen or chlorine atom or --OR.sub.21a group where R.sub.21a is --COR.sub.21b where R.sub.21b is defined in claim 1.
- 16. A process for preparing a 5.alpha.-17.alpha.,21-dihydroxy steroid of the formula ##STR5## which comprises: (1) blocking the side chain of a .DELTA..sup.4 -17.alpha.,21-dihydroxy-20-keto steroid of the formula ##STR6## by reaction with an aldehyde of the formula R--CHO to give a .DELTA..sup.4 -17,21-blocked steroid of the formula ##STR7## (2) reducing the .DELTA..sup.4 -double bond by reaction with a metal-amine to give the 5.alpha.-17.alpha.,21-blocked steroid of the formula ##STR8## and (3) removing the 17,21-blocking group where R.sub.6, R.sub.11, R.sub.16.alpha. and R.sub.16.beta. are defined in claim 1 and where R is a hydrogen atom or alkyl group of 1 through 4 carbon atoms.
- 17. A process according to claim 16 wherein R.sub.16.alpha. is a methyl group.
- 18. A process according to claim 16 where R.sub.16.beta. is a methyl group.
- 19. A process according to claim 16 where R.sub.16.alpha. and R.sub.16.beta. are both hydrogen atoms.
- 20. A process according to claim 16 where the 17,21-blocking group is removed with dilute acid.
- 21. A process according to claim 16 where the lithium-ammonia reduction is performed at less than -35.degree..
- 22. A process according to claim 16 where the metal of the metal-amine is lithium or sodium.
- 23. A process according to claim 22 where the metal is lithium.
- 24. A process according to claim 16 where the amine of the metal-amine is selected from the group consisting of ammonia, methylamine, ethylamine or ethylenediamine.
- 25. A process according to claim 24 where the amine is ammonia.
- 26. A process according to claim 25 where the metal-amine is selected from the group consisting of lithium-ammonia or sodium-ammonia.
- 27. A process according to claim 16 where R is a hydrogen atom.
- 28. A compound according to claim 1 which is 17.alpha.,21-dihydroxy-16.beta.-methyl-5.beta.-pregn-9(11)-ene-3,20-dione 17,21-dipropionate.
- 29. A compound according to claim 1 which is 17.alpha.,21-dihydroxy-16.alpha.-methyl-5.beta.-pregn-9(11)-ene-3,20-dione 17,21-dipropionate.
- 30. A compound according to claim 1 which is 17.alpha.,21-dihydroxy-5.beta.-pregn-9(11)-ene-3,20-dione 17,21-dipropionate.
- 31. A compound according to claim 1 which is 17.alpha.,21-dihydroxy-16.beta.-methyl-5.beta.-pregn-9(11)-ene-3,20-dione 17-propionate 21-mesylate.
- 32. A compound according to claim 1 which is 17.alpha.,21-dihydroxy-16.alpha.-methyl-5.beta.-pregna-9(11)-ene-3,20-dione 17-propionate 21-mesylate.
- 33. A compound according to claim 1 which is 17.alpha.,21-dihydroxy-5.beta.-pregna-9(11)-ene-3,20-dione 17-propionate 21-mesylate.
- 34. A compound according to claim 1 which is 21-chloro-17.alpha.-hydroxy-16.beta.-methyl-5.beta.-pregn-9(11)-ene-3,20-dione 17-propionate.
- 35. A compound according to claim 1 which is 21-chloro-17.alpha.-hydroxy-16.alpha.-methyl-5.beta.-pregn-9(11)-ene-3,20-dione 17-propionate.
- 36. A compound according to claim 1 which is 21-chloro-17.alpha.-hydroxy-5.beta.-pregn-9(11)-ene-3,20-dione 17-propionate.
- 37. A compound according to claim 3 which is 17.alpha.,21-dihydroxy-16.beta.-methyl-5.alpha.-pregn-9(11)-ene-3,20-dione 17-propionate.
- 38. A compound according to claim 3 which is 17.alpha.,21-dihydroxy-16.beta.-methyl-5.alpha.-pregn-9(11)-ene-3,20-dione 17-acetate.
- 39. A compound according to claim 3 which is 17.alpha.,21-dihydroxy-16.beta.-methyl-5.alpha.-pregn-9(11)-ene-3,20-dione 17-butyrate.
- 40. A compound according to claim 3 which is 17.alpha.,21-dihydroxy-16.beta.-methyl-5.alpha.-pregn-9(11)-ene-3,20-dione 17-valerate.
- 41. A compound according to claim 3 which is 17.alpha.,21-dihydroxy-16.beta.-methyl-5.alpha.-pregn-9(11)-ene-3,20-dione 17-benzoate.
- 42. A compound according to claim 4 which is 17.alpha.,21-dihydroxy-16.alpha.-methyl-5.alpha.-pregn-9(11)-ene-3,20-dione 17-acetate.
- 43. A compound according to claim 4 which is 17.alpha.,21-dihydroxy-16.alpha.-methyl-5.alpha.-pregn-9(11)-ene-3,20-dione 17-propionate.
- 44. A compound according to claim 4 which is 17.alpha.,21-dihydroxy-16.alpha.-methyl-5.alpha.-pregn-9(11)-ene-3,20-dione 17-butyrate.
- 45. A compound according to claim 4 which is 17.alpha.,21-dihydroxy-16.alpha.-methyl-5.alpha.-pregn-9(11)-ene-3,20-dione 17-valerate.
- 46. A compound according to claim 4 which is 17.alpha.,21-dihydroxy-16.alpha.-methyl-5.alpha.-pregn-9(11)-ene-3,20-dione 17-benzoate.
- 47. A compound according to claim 5 which is 17.alpha.,21-dihydroxy-5.alpha.-pregn-9(11)-ene-3,20-dione 17-acetate.
- 48. A compound according to claim 5 which is 17.alpha.,21-dihydroxy-5.alpha.-pregn-9(11)-ene-3,20-dione 17-propionate.
- 49. A compound according to claim 5 which is 17.alpha.,21-dihydroxy-5.alpha.-pregn-9(11)-ene-3,20-dione 17-butyrate.
- 50. A compound according to claim 5 which is 17.alpha.,21-dihydroxy-5.alpha.-pregn-9(11)-ene-3,20-dione 17-valerate.
- 51. A compound according to claim 5 which is 17.alpha.,21-dihydroxy-5.alpha.-pregn-9(11)-ene-3,20-dione 17-benzoate.
- 52. A process according to claim 7 where the 5.beta.-.DELTA..sup.9(11) -steroid (III) is 17.alpha.,21-dihydroxy-16.beta.-methyl-5.beta.-pregn-9(11)-ene-3,20-dione 17,21-dipropionate.
- 53. A process according to claim 7 where the 5.beta.-.DELTA..sup.9(11) -steroid (III) is 17.alpha.,21-dihydroxy-16.alpha.-methyl-5.beta.-pregn-9(11)-ene-3,20-dione 17,21-dipropionate.
- 54. A process according to claim 7 where the 5.beta.-.DELTA..sup.9(11) -steroid (III) is 17.alpha.,21-dihydroxy-5.beta.-pregn-9(11)-ene-3,20-dione 17,21-dipropionate.
- 55. A process according to claim 7 where the 5.beta.-.DELTA..sup.9(11) -steroid (III) is 17.alpha.,21-dihydroxy-16.beta.-methyl-5.beta.-pregn-9(11)-ene-3,20-dione 17-propionate 21-mesylate.
- 56. A process according to claim 7 where the 5.beta.-.DELTA..sup.9(11) -steroid (III) is 17.alpha.,21-dihydroxy-16.alpha.-methyl-5.beta.-pregna-9(11)-ene-3,20-dione 17-propionate 21-mesylate.
- 57. A process according to claim 7 where the 5.beta.-.DELTA..sup.9(11) -steroid (III) is 17.alpha.,21-dihydroxy-5.beta.-pregna-9(11)-ene-3,20-dione 17-propionate 21-mesylate.
- 58. A process according to claim 7 where the 5.beta.-.DELTA..sup.9(11) -steroid (III) is 21-chloro-17.alpha.-hydroxy-16.beta.-methyl-5.beta.-pregn-9(11)-ene-3,20-dione 17-propionate.
- 59. A process according to claim 7 where the 5.beta.-.DELTA.9(11)-steroid (III) is 21-chloro-17.alpha.-hydroxy-16.alpha.-methyl-5.beta.-pregn-9-(11)-ene-3,20-dione 17-propionate.
- 60. A process according to claim 7 where the 5.beta.-.DELTA.9(11)-steroid (III) is 21-chloro-17.alpha.-hydroxy-5.beta.-pregn-9(11)-ene-3,20-dione 17-propionate.
Parent Case Info
This is a division of application Ser. No. 117,401, filed Jan. 31, 1980 now U.S. Pat. No. 4,318,853.
US Referenced Citations (3)
Number |
Name |
Date |
Kind |
3055922 |
Krakower et al. |
Mar 1970 |
|
3992422 |
Green et al. |
Nov 1976 |
|
4336200 |
Ayer et al. |
Jun 1982 |
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Divisions (1)
|
Number |
Date |
Country |
Parent |
117401 |
Mar 1980 |
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