JPH0361679B2 - - Google Patents

Info

Publication number: JPH0361679B2
Authority: JP; Japan
Prior art keywords: group; compound; yield; dihydroxy; general formula
Prior art date: 1983-08-26
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

JP15492683A

Other languages

English (en)

Japanese (ja)

Other versions

JPS6048998A (ja

Inventor

Saburo Sugai

Tokuji Okazaki

Mitsuya Akaboshi

Shiro Ikegami

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

OTA PHARMA

Original Assignee

OTA PHARMA

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1983-08-26

Filing date

1983-08-26

Publication date

1991-09-20

1983-08-26 Application filed by OTA PHARMA filed Critical OTA PHARMA

1983-08-26 Priority to JP15492683A priority Critical patent/JPS6048998A/ja

1985-03-16 Publication of JPS6048998A publication Critical patent/JPS6048998A/ja

1991-09-20 Publication of JPH0361679B2 publication Critical patent/JPH0361679B2/ja

Status Granted legal-status Critical Current

Links

VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 30
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 9
239000011973 solid acid Substances 0.000 claims description 8
150000003431 steroids Chemical class 0.000 claims description 8
125000000217 alkyl group Chemical group 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
239000000377 silicon dioxide Substances 0.000 claims description 6
125000004423 acyloxy group Chemical group 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000003710 aryl alkyl group Chemical group 0.000 claims description 2
125000003118 aryl group Chemical group 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
125000004043 oxo group Chemical group O=* 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
150000001875 compounds Chemical class 0.000 description 34
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
238000000034 method Methods 0.000 description 25
239000000706 filtrate Substances 0.000 description 20
239000007795 chemical reaction product Substances 0.000 description 19
239000012043 crude product Substances 0.000 description 19
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
238000004519 manufacturing process Methods 0.000 description 18
-1 20-oxopregnan steroid Chemical class 0.000 description 16
VHRSUDSXCMQTMA-PJHHCJLFSA-N 6alpha-methylprednisolone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)CO)CC[C@H]21 VHRSUDSXCMQTMA-PJHHCJLFSA-N 0.000 description 15
238000003756 stirring Methods 0.000 description 15
238000012746 preparative thin layer chromatography Methods 0.000 description 14
239000000741 silica gel Substances 0.000 description 13
229910002027 silica gel Inorganic materials 0.000 description 13
239000002253 acid Substances 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 11
239000002585 base Substances 0.000 description 10
YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 9
239000004927 clay Substances 0.000 description 8
239000000203 mixture Substances 0.000 description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 6
238000007796 conventional method Methods 0.000 description 5
230000000704 physical effect Effects 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
238000004809 thin layer chromatography Methods 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
238000000921 elemental analysis Methods 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
229960000890 hydrocortisone Drugs 0.000 description 3
239000000047 product Substances 0.000 description 3
239000007858 starting material Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
GUHFLRTWNHWJBS-VLTGGNAYSA-N (8r,9s,10s,13s)-17-acetyl-10,13-dimethyl-1,2,4,5,6,7,8,9,11,12-decahydrocyclopenta[a]phenanthren-3-one Chemical compound C1CC2CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1C1=CC=C(C(=O)C)[C@@]1(C)CC2 GUHFLRTWNHWJBS-VLTGGNAYSA-N 0.000 description 2
XUXVVQKJULMMKX-UHFFFAOYSA-N 1,1,1-trimethoxypentane Chemical compound CCCCC(OC)(OC)OC XUXVVQKJULMMKX-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
239000005995 Aluminium silicate Substances 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
239000005909 Kieselgur Substances 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
239000003377 acid catalyst Substances 0.000 description 2
239000003470 adrenal cortex hormone Substances 0.000 description 2
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
229910052782 aluminium Inorganic materials 0.000 description 2
235000012211 aluminium silicate Nutrition 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
239000000440 bentonite Substances 0.000 description 2
229910000278 bentonite Inorganic materials 0.000 description 2
SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
229960002537 betamethasone Drugs 0.000 description 2
UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
239000013078 crystal Substances 0.000 description 2
238000000354 decomposition reaction Methods 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000010451 perlite Substances 0.000 description 2
235000019362 perlite Nutrition 0.000 description 2
229960005205 prednisolone Drugs 0.000 description 2
OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
238000003385 ring cleavage reaction Methods 0.000 description 2
235000012239 silicon dioxide Nutrition 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
ABUISBDTYAZRHY-RBKZJGKHSA-N (6s,8s,9r,10s,11s,13s,14s,17r)-6,9-difluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3C[C@H](F)C2=C1 ABUISBDTYAZRHY-RBKZJGKHSA-N 0.000 description 1
YZZVVLUNOZJXCM-DADBAOPHSA-N (8s,9s,10r,13s,14s,17s)-17-acetyl-10,13-dimethyl-7,8,9,12,14,15,16,17-octahydro-6h-cyclopenta[a]phenanthrene-3,11-dione Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2=O YZZVVLUNOZJXCM-DADBAOPHSA-N 0.000 description 1
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
OCFYTOIAJLLHDS-UHFFFAOYSA-N 1-ethoxybutane-1,1-diol Chemical compound CCCC(O)(O)OCC OCFYTOIAJLLHDS-UHFFFAOYSA-N 0.000 description 1
JXCCXEDUYUNYNB-UHFFFAOYSA-N 1-methoxy-2-methylpropane-1,1-diol Chemical compound COC(O)(O)C(C)C JXCCXEDUYUNYNB-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
RBXTZMSXJRIXSV-ZEQQQVMLSA-N CCC(=S)OCC([C@H]1CC[C@H]2[C@@H]3CCC4=CC(C=C[C@]4(C)[C@H]3CC[C@]12C)=O)=O Chemical compound CCC(=S)OCC([C@H]1CC[C@H]2[C@@H]3CCC4=CC(C=C[C@]4(C)[C@H]3CC[C@]12C)=O)=O RBXTZMSXJRIXSV-ZEQQQVMLSA-N 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
OGFRCKORMIKXHH-MWGRHRFLSA-N [(8R,9S,10R,13S,14S,17R)-10,13-dimethyl-3-oxo-17-propanoyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-yl] propanoate Chemical compound CCC([C@]1(CC[C@H]2[C@@H]3CCC4=CC(C=C[C@]4(C)[C@H]3CC[C@]12C)=O)OC(CC)=O)=O OGFRCKORMIKXHH-MWGRHRFLSA-N 0.000 description 1
SIKHQNIGPLUJDX-ZEQQQVMLSA-N [2-[(8s,9s,10r,13s,14s,17s)-10,13-dimethyl-3-oxo-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl] propanoate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)COC(=O)CC)[C@@]1(C)CC2 SIKHQNIGPLUJDX-ZEQQQVMLSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000003513 alkali Substances 0.000 description 1
230000009285 allergic inflammation Effects 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
229940092705 beclomethasone Drugs 0.000 description 1
235000012216 bentonite Nutrition 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
SHFGJEQAOUMGJM-UHFFFAOYSA-N dialuminum dipotassium disodium dioxosilane iron(3+) oxocalcium oxomagnesium oxygen(2-) Chemical compound [O--].[O--].[O--].[O--].[O--].[O--].[O--].[O--].[Na+].[Na+].[Al+3].[Al+3].[K+].[K+].[Fe+3].[Fe+3].O=[Mg].O=[Ca].O=[Si]=O SHFGJEQAOUMGJM-UHFFFAOYSA-N 0.000 description 1
HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical class O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000003814 drug Substances 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
238000001914 filtration Methods 0.000 description 1
KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
229960004584 methylprednisolone Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000005445 natural material Substances 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
229960004618 prednisone Drugs 0.000 description 1
XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
238000000039 preparative column chromatography Methods 0.000 description 1
239000002994 raw material Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
206010039073 rheumatoid arthritis Diseases 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
125000005624 silicic acid group Chemical class 0.000 description 1
208000017520 skin disease Diseases 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000002904 solvent Substances 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
229920002994 synthetic fiber Polymers 0.000 description 1
238000005406 washing Methods 0.000 description 1

Landscapes

Steroid Compounds (AREA)

JP15492683A 1983-08-26 1983-08-26 プレグナン系ステロイド１７α−エステル化合物の製造法 Granted JPS6048998A (ja)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
JP15492683A JPS6048998A (ja)	1983-08-26	1983-08-26	プレグナン系ステロイド１７α−エステル化合物の製造法

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
JP15492683A JPS6048998A (ja)	1983-08-26	1983-08-26	プレグナン系ステロイド１７α−エステル化合物の製造法

Publications (2)

Publication Number	Publication Date
JPS6048998A JPS6048998A (ja)	1985-03-16
JPH0361679B2 true JPH0361679B2 (de)	1991-09-20

Family

ID=15594964

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP15492683A Granted JPS6048998A (ja)	1983-08-26	1983-08-26	プレグナン系ステロイド１７α−エステル化合物の製造法

Country Status (1)

Country	Link
JP (1)	JPS6048998A (de)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH06296381A (ja) *	1994-03-23	1994-10-21	Ricoh Co Ltd	駆動制御装置

1983
- 1983-08-26 JP JP15492683A patent/JPS6048998A/ja active Granted

Also Published As

Publication number	Publication date
JPS6048998A (ja)	1985-03-16

Publication	Publication Date	Title
JPS6228158B2 (de)	1987-06-18
JPH0665286A (ja)	1994-03-08	１１−ケトステロイド誘導体の新製造法
EP0532562B1 (de)	1994-11-23	VERFAHREN ZUR HERSTELLUNG VON 10$g(b)-H-STEROIDEN
EP0201452B1 (de)	1989-08-09	Verfahren zur Herstellung von 17alpha-Ethinyl-17beta-hydroxy-18-methyl-4,15-estradien-3-on und die neuen Ausgangsverbindungen für dieses Verfahren
JPH0361679B2 (de)	1991-09-20
JPS62142197A (ja)	1987-06-25	ステロイド類
JPH0276896A (ja)	1990-03-16	ステロイド化合物およびその製造方法
EP0187847A1 (de)	1986-07-23	VERFAHREN ZUR HERSTELLUNG VON 6$g(A)-METHYLSTEROIDEN
US4368160A (en)	1983-01-11	Process for preparing 17α-hydroxy-pregn-4-en-3,20-dione derivatives
HU187843B (en)	1986-02-28	Process for producing 17-alpha-hydroxy-17-beta-bracket-hydroxy-acetyl-bracket closed-steroides
JPH0122280B2 (de)	1989-04-25
US3167544A (en)	1965-01-26	Process for the preparation of nicotinic acid esters of steroid compounds
US4482494A (en)	1984-11-13	Process for preparing 17α-hydroxy-pregn-4-en-3,20-dione
AU636433B2 (en)	1993-04-29	Process for dehydrating corticosteroid intermediates
JPH0123476B2 (de)	1989-05-02
JPH0565294A (ja)	1993-03-19	２０−イソシアノ−２０−スルホニル−デルタ１６−ステロイド及びその製造方法
JPS61112095A (ja)	1986-05-30	新規ステロイドおよびその調整方法
KR20240048007A (ko)	2024-04-12	Δ9,11 스테로이드 합성
JP2714392B2 (ja)	1998-02-16	ステロイド誘導体の製造法
JPS6118559B2 (de)	1986-05-13
JPS6352633B2 (de)	1988-10-19
JPS6353995B2 (de)	1988-10-26
DE2749104A1 (de)	1979-05-03	Delta hoch 15 -steroide
JPS6353998B2 (de)	1988-10-26
IL38143A (en)	1977-08-31	Process for the preparation of 11,12-enolates of 9alpha-halo-11-keto steroids and of 9alpha,12-dihalo or 9alpha,12,12,12-trihalo 11-keto(or11-hydroxy)steroids