IE44551B1 - The preparation of corticoids - Google Patents
The preparation of corticoidsInfo
- Publication number
- IE44551B1 IE44551B1 IE2356/78A IE235678A IE44551B1 IE 44551 B1 IE44551 B1 IE 44551B1 IE 2356/78 A IE2356/78 A IE 2356/78A IE 235678 A IE235678 A IE 235678A IE 44551 B1 IE44551 B1 IE 44551B1
- Authority
- IE
- Ireland
- Prior art keywords
- hydrogen
- carbon atoms
- bond
- formula
- single bond
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 150000004965 peroxy acids Chemical class 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 150000003431 steroids Chemical class 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003435 aroyl group Chemical group 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 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
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- -1 phenylacetyl Chemical group 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- RKHQGWMMUURILY-UHRZLXHJSA-N cortivazol Chemical compound C([C@H]1[C@@H]2C[C@H]([C@]([C@@]2(C)C[C@H](O)[C@@H]1[C@@]1(C)C2)(O)C(=O)COC(C)=O)C)=C(C)C1=CC1=C2C=NN1C1=CC=CC=C1 RKHQGWMMUURILY-UHRZLXHJSA-N 0.000 description 1
- LNGNZSMIUVQZOX-UHFFFAOYSA-L disodium;dioxido(sulfanylidene)-$l^{4}-sulfane Chemical compound [Na+].[Na+].[O-]S([O-])=S LNGNZSMIUVQZOX-UHFFFAOYSA-L 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
Landscapes
- Steroid Compounds (AREA)
Description
The present invention relates to a novel process for .preparing corticoids.
According to the invention, a process for the preparation of a steroid of the formula
Ch2-or21
wherein either is an oxygen atom and there are double bonds : between C-3 and R- and between C-4 and C-5 and a single bond between C-5 and C-6, or R^ is a /5 -hydroxylgroup and there is . a single bond between C-3 and R^ and between C-4 and C-5 and a double bond between C-5 and C-6; Rg is hydrogen, fluorine or methyl; Rg is' hydrogen, fluorine, chlorine, bromine or hydroxy: H-f-j is (i) hydrogen, in which case there is a single bond . between C-11 and R^ and a single or double bond between C-9 and C-11, (ii) oL -hydroxy or ί> -hydroxy, in which case there are single bonds between C-11 and R^ and between C-9 and C-11 or (iii) oxygen, in which case there is a double bond between C-11 and.R^ and a single bond between C-9 and C-11;
R^g is hydrogen, tZ-methyl or/-methyl; the 1,2 bond is a single bond or a double bond; and R^ is hydrogen, alkanoyl of 2 to
-244SS1 carbon atoms or aroyl or aralkanoyl of 7 to 12 carbon atoms, which comprises reacting a compound of the formula
II
CH,
• wherein Ry Rg, Rg, R^ , R^g and---are as defined above and Z is -OR2q, -SR^go or -Ii(R120^2 in whicil R20 of one to 5 carbon atoms, phenyl or phenyl substituted by an alkyl radical of one to 4 carbon atoms, or aralkyl of 7 to 12 carbon atoms and R-jgQ is alkyl of one to 5 carbon atoms, with a peracid of the formula R2200H, wherein R22 is the same as R^ as defined above but is not hydrogen, in an organic solvent, and, if desired, hydrolysing the ester which is formed to give the desired'steroid in which R^
- is hydrogen.
The compounds of formula IX are described and claimed in - Patent Specification No. 44549 .. together with a process for their preparation.
For the peracid of formula R2200H, examples of R22 as alkanoyl of 2 to 6 carbon atoms are acetyl, propionyl,.
-3butyryl, valeryl, hexanoyl and isomers thereof; and examples of aroyl and aralkanoyl of 7 to 12 carbon atoms are benzoyl, phenylacetyl, phenylpropionyl, phenylbutyryl, phenylvaleryl, phenylhexanoyl and isomers thereof.
By way of example, if,as is preferred, the peracid is peracetic acid, then.the product is the 21-acetate of the corticoid .product . .. The reaction is carried out in an organic solvent or mixture of solvents such as benzene, ethyl acetate, acetone and/or chloroform·. A base such as sodium .' .acetate is added to the organic solvent so as to neutralise • the sulphuric acid present in the commercially produced peracids which are used in this process. The reaction may.be carried out at a temperature of from -30°C to 25°C., • preferably from 0° to 5°C. It is preferred that the reaction is carried out under an inert dry gas such as nitrogen,
When the reaction is complete as measured by thin layer
--: chromatography, it is quenched with an agent such as sodium .- sulphite or sodium hydrosulphite. The reaction can then be worked up by conventional means.
The following Example illustrates the invention.
NMR (nuclear magnetic resonance) spectra were recorded .
on a Varian A-60 spectrophotometer with tetramethylsilane (TMS) as an internal standard, and the chemical shifts were reported in ppm (δ ) relative to TMS, TMS=0.000 S. Varian is a registered Trade Mark.
Melting points were determined on a Thomas Hoover . Capillary melting point apparatus.
UV (ultraviolet) spectra were determined on a Beckmann
-44 4 8 51
DV Model 2400 Spectrophotometer.
Optical rotations were determined on a Perkin-Elmer
Polarimeter.
Example 17<^,21-Dihydroxypregn-4-ene-3,20-dione 21-acetate (Formula XII: R^ is an oxygen atom, Rg, Rg, R^ and R^g are hydrogen, R21 is acetyl and the 1,2 and 9,11 bonds are single bonds).
A mixture of 17e<-hydroxy-20-methoxypregna-4,20-dien-3-one (3.0 g., Example 1 Of Patent Specification No. 4454'9·' methylene chloride (45 ml.), ethyl acetate (75 ml.) and anhydrous sodium acetate (3.0 g.) is cooled to 0 - 5°C. under nitrogen with stirring. To this mixture is added 2.26 ml. of 40 percent peracetic acid. The slurry is stirred at 0 - 5°C. for 2 hr. The reaction is quenched by the addition of aqueous sodium thiosulphite solution. The layers are separated and the organic layer is washed with a solution of sodium bicarbonate (1.0 g.) in deionised water (30 ml.). The organic layer is then washed with two 30 ml. portions of deionised water and one 30 ml. portion of a saturated aqueous solution of sodium chloride. The organic layer is then dried over anhydrous magnesium sulphate. The dried solution is concentrated to a thick crystalline slurry under reduced pressure. Methanol is added and the resulting slurry is concentrated to a low volume under reduced pressure and filtered. The solids are washed with a little methanol previously cooled to about 0°C. and then dried under vacuum at 65°C. to give 2.309 g. of the title compound, m.p. 229-235.5°; NMR (CDC13) = 0.71, 1.19, 4.98, and 5.73 S and is identical to an authentic sample; UV (methanol) -λ-max. = 242 mji
-54 45 5’(ε = 17,055): [jkJq acetone + 107.8°.
An alternative process for preparing corticoids of formula
XII from compounds of formula IX is described and claimed in Patent Specification No. 43959.
Claims (2)
1. A process for the preparation of a steroid of the formula ch 2 -or 21 wherein either R^ is an oxygen atom and there are double bonds 5 between C-3 and and between C-4 and C-5 and a single bond between C-5 and C-6, or R^ is a /3-hydroxyl group and there is a single bond between C-3 and R^ and between C-4 and C-5 and a double bond between C-5 and C-6; Rg is hydrogen, fluorine or methyl; Rg is hydrogen, fluorine, chlorine, bromine or 1° hydroxy; R^ is (i) hydrogen, in which case there is a single bond between C-11 and R^ and a single or double bond between C-9 and C-11, (ii) -hydroxy or β -hydroxy, in which case there are single bonds between C-11 and R^ and between C-9 and C-11 or (iii) oxygen, in which case there is a double bond 15 between C-11 and R^ and a single bond between C-9 and C-11; R^g is hydrogen, «.-methyl or /^-methyl; the 1,2 bond is a single bond or a double bond; and R 21 is hydrogen, alkanoyl of 2 to 6 carbon atoms or aroyl or aralkanoyl of 7 to 12 carbon -7atoms, which comprises reacting a compound of the formula .Wherein R^, Rg, Rg, R^, R^g and ·— are as defined above and Z is -0R 20 , -SR 12O or ” N ^ R 120^2 in which R ?o ls alk y 1 of one to 5 carbon atoms, phenyl or phenyl substituted by an alkyl radical of one to 4 carbon atoms, or aralkyl of 7 to 12 carbon atoms and R^2q is alR y· 1 · one 5 carbon atoms with a peracid of the formula R2200H, wherein R 22 is the same as R^ as defined above but is not hydrogen, in an organic solvent, and, if desired, hydrolysing the ester which is formed to give the desired steroid in which R^ is hydrogen.
2. A process according to claim 1 substantially as described in. the Example.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/632,671 US4041055A (en) | 1975-11-17 | 1975-11-17 | Process for the preparation of 17α-hydroxyprogesterones and corticoids from androstenes |
| IE2537/76A IE44548B1 (en) | 1975-11-17 | 1976-11-17 | Sulfoxides and their preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE44551L IE44551L (en) | 1977-05-17 |
| IE44551B1 true IE44551B1 (en) | 1982-01-13 |
Family
ID=26319276
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE2356/78A IE44551B1 (en) | 1975-11-17 | 1976-11-17 | The preparation of corticoids |
| IE2355/78A IE44550B1 (en) | 1975-11-17 | 1976-11-17 | The preparation of 21-halosteroids |
| IE2354/78A IE44549B1 (en) | 1975-11-17 | 1976-11-17 | 17 -hydroxy-20-substituted- 20-steroids |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE2355/78A IE44550B1 (en) | 1975-11-17 | 1976-11-17 | The preparation of 21-halosteroids |
| IE2354/78A IE44549B1 (en) | 1975-11-17 | 1976-11-17 | 17 -hydroxy-20-substituted- 20-steroids |
Country Status (1)
| Country | Link |
|---|---|
| IE (3) | IE44551B1 (en) |
-
1976
- 1976-11-17 IE IE2356/78A patent/IE44551B1/en unknown
- 1976-11-17 IE IE2355/78A patent/IE44550B1/en unknown
- 1976-11-17 IE IE2354/78A patent/IE44549B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IE44551L (en) | 1977-05-17 |
| IE44550L (en) | 1977-05-17 |
| IE44550B1 (en) | 1981-12-30 |
| IE44549B1 (en) | 1981-12-30 |
| IE44549L (en) | 1977-05-17 |
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