IL27182A - Method for the preparation of 22-hydroxy-6-ketosteroids from 20-formyl-6-ketosteroids - Google Patents
Method for the preparation of 22-hydroxy-6-ketosteroids from 20-formyl-6-ketosteroidsInfo
- Publication number
- IL27182A IL27182A IL2718266A IL2718266A IL27182A IL 27182 A IL27182 A IL 27182A IL 2718266 A IL2718266 A IL 2718266A IL 2718266 A IL2718266 A IL 2718266A IL 27182 A IL27182 A IL 27182A
- Authority
- IL
- Israel
- Prior art keywords
- group
- reaction
- hydrogen
- carried out
- denotes
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Description
for the Preparation of from The invention relates to a method for the tion of compounds of generalformula in a preferably low or acyl hydrogen or a Z hydrogen or Y a linear or or alkinyl group containing at least 3 carbon atoms which may ally be by free or functionally modified or an ethinyl C a 8 saturated or unsaturated and A the in the and which may contain additional subs uents in the molecule whic are inert towards the reagents used according to the and in which the hydrogen atom the the methyl group the and the in the may have or by subjecting a corresponding pound to a selective Grignard reaction in the by means of in which Y denotes the group described above and denotes bromine and sequently optionally selectively any saturated bond present in ally esterifying or etherifying other hydroxyl groups than the group which may be saponifying acyloxy groups which are present eliminating ether also do not occur If Grignard reagent is allowed to act on the starting steroid over a longer about According to the sible preferred Grignard reagents of the given above those in which Y represents and other similar alk 1 or alkinyl Those in which the or alkinyl group is branched are particularly If the group Y additionally contains a hydroxy1 as in then this grou is advisably as the After the reaction has taken place this protective group can optionally again be If the group Y introduced by means of the Grignard reaction is then the optional subsequent selective of the unsaturated group Y carried out the presence of metal like the Invention contain additional acyloxy in particular a then these are converted in o free groups in the course of the hydrogenation if alysts ar used in the presence of alcohols as It should furthermore he noted in the hydrogenation reaction tha primary products in which denotes a hydroxyl group are less suitable for the selective genation of the invention beeause the a least partial elimination of the group in the course of the hydrogenation can barely be If therefore the ultimately desired products of the method are hydroxylaied compounds having at the same time a then it is advisable either only to duce the hydroxyl group after the unsaturated Y group has been or to the ultimately desired saturated group directly into starting The which may take place ly is carried out by methods of steroid chemistry which are in themselves purely chemical it ifl particular takes place by reaction with Using biochemical the in particular takes place by the action of organisms of the enzymes by which are known to be preferential 1 like enzymes of the type ably Curvularia or of the ably Absidia or especially of the preferably Heliocostylum pi or of the The esterifieation or of hydroxyl groups which are presen or the of groups or elimination of ether groups also of other protective which may optionally be carried out in the course of the method of the invention place by methods which are in themselves The appropriate reaction conditions this are determined by the nature of the substituent similarly to the ease of the selective If group then reaction conditions under whic it is known that tertiary hydroxyl groups easily eliminated elimina of water should be The optional subsequent esterifieatio of othe hydroxyl groups than OH group then take place by of for acid anhydrides or acid halides in the presence of As already explained the selective of the reaction of the invention was not to be pected on the basis of working methods known to the This process stage is thus new and of inventive and for this reason specific protection for it the framework of the present method of the The method which may be produced accordin to the method of the invention in part themselves possess valuable pharmacological or serve as mediates for preparation of active substances of the most diverse hormone The products of the method are particularly suitable as intermediate for the preparation of insect metamorphosis A preferred starting product of the method of the vention is the 20 3 diacetate which has hitherto been The for which no protection is claimed the framework of the present takes in the followin 275 ic acid are added with cooling to a solution of 331 g of 3 acid methyl o 54 4679 in 3300 ml of methylene after addition of 80 g of potassium acetate g of sodium The reaction mixture is stirred for 2 hours at treated water and diluted with lene The separated methylene chloride phase is washed with sodium carbonate solution and dried over sodium and evaporated in The epoxide so is dissolved in 250C ml of treated with 690 ml of 3 perchloric and heated under reflux for 5 solution is stirred into 1 of ice and the precipitated dione is filtered washed and The 5 acid methyl ester is recr stallised from ethyl acetate and melts at A solution of 33 ml of bromine and g of sium acetate in 50 ml of glacial acetic acid is added dropwise to g of ic acid methyl ester in 800 ml of with ice The reaction solution poured into ice water containing sodium and the precipitated 2 acid methyl ester acid methyl ester in 240 ml of are reduced at by means of a solution of g of lithium in 160 ml of The mixture is stirred into ice water containing sulphuric and the precipitate is filtered off and recrystallised from ethyl The acid methyl ester melts at 4 g of acid methyl ester 80 ml of pyridine are allowed to stand with 40 ml of acetic anhydride for 20 hours at room and are then stirred The precipitate formed is off and crystallised from The nan aeid methyl so obtained melts at g of carboxylic acid methyl in 800 ml of glacial acetic acid and ml of water are heated with 50 g of silver acetate for 20 hours under The precipitate is filtered off and the filtrate is stirred ice The precipitated reaction product is filtered washed until neutral and After recrystalllsation from g of carboxylic acid methyl ester are obtained as the 5 isomer g of the above isomer mixture are dissolved in 500 ml of glacial acetic treated with g of bromine in 50 ml of acetic acid and stirred for filtered washed until neutral and After recrystallisation from g of 7 yl acid methyl ester in 380 ml of are heated with g of carbonate and g of lithium bromide for hours under nitrogen to The undissolved lithium salts are filtered off and the filtrate is stirred ice ated reaction product if filtered off dried and subjected to chromatography on silica gel recrystallisation from ethe methylene chloride of acid methyl ester are obtained Melting point 10 g of carboxylie acid methyl ester In 100 ml of are heated under reflux for 2 hours with 12 g of anhydrous lithium The mixture precipitated water ø acidified hydrochloric and saturated with sodium chloride The precipitated reaction product is filtered dissolved in methylene chloride and twice subjected carboxylie acid n 3 m of abso u e tetrahydrofurane are heated for 20 minutes under reflux with 10 g of acidified with hydrochloric acid saturated with sodium precipitated is filtered off and Yield 2 g of the imidasolide so obtained 40 ml of are stirred with 2 g of lithium minium for 1 hour at room S e mixture is stirred into ice fied with hydrochloric and extracted with after buffering wit sodium After methanol was heated at boiling 30 The resulting reaction after was poured into wate the organic phase was dried and The crude on in admixtur with 200 milliliters of pyridine and g of sulfonyl was held at room temperature for After dilution of the mixture with the precipitate which had formed was separated off and dissolved in methylene The was dried and concentrated to yield A 7 22 3 after crystallization from diisopropyl melted at A of g in 10 ml of dlmethylaniline was heated at for 20 After the reaction solution was poured into dilute sulfuric and the precipitate which formed was filtered off by suction and taken up i The organic solution was washed until and concentrated to yield After dissolvin e crude product 130 ml of acetic acid at there was successively added ml g of silver acetate and g of finely powdered The resulting mixture was heated with vigorous stirring at 50 addition of an excess of common the reaction ture was stirred for an additional 5 filtered and the filtrate concentrated dryness residue was purified by preparative thin layer and after recr s allisation from diisopropyl A solution of g of 7 92 in 80 each of absolute pyridine acetic anhydride was to stand at A solution of 4 g 2 in 750 ml of chloride and 500 of methanol was treated at over a 7 10 of ozone which was supplied in an gen After the addition of 15 of the mixture stirred for 30 decomposed with water and extracted ing of the ether extracts afforded a crude product which evaporated off in and the residue recrystallised to an bromide solution 244 mg of and ml of ethyl bromide in 15 ml heated with 100 mg of selenium diox de for 1 hour to The 14 separated from the selenium by preparative thin film without and recrystallised from 232 to of hitherto not been is prepared as 467 g is converted into melting at by epoxydatlon and subsequent with perchloric The dione is converted into melting at by reduction and After reaction with silver acetate and subsequent melting at is obtained and is converted in the melting at after elimination of hydrogen To a solution of ethyl magnesium bromide from 2 g of magnesium ml of ethyl bromide in of there was added dropwise a solution of 16 ml o in 100 ml of The reaction solution was stirred for 30 minutes at room temperature and then added dropwise is 200 of at The temperature of the action mixture was allowed to rise to whereupon the mixture was decomposed the addition of ammonium chloride Extraction with afforded a crude product which was chrematographed on 200 g fractions by elution with 2 liters of were The product was with chloroform containing 10 per cent of methanol and again chromatographed on 140 g of removal of undesired benzene and benzene containing 1 per cent Melting point isopropyl le 7 in 50 ml of methanol was hydrogenated in the presence of 200 of platinum until the uptake of 75 of After there was obtained insufficientOCRQuality
Claims (1)
1. particularly described ascertained the nature of our said inventio and in what manner the same is to be performed we declare that what we claim Method for th preparation of compounds of general formula in which eno es y rogen o a preferably low or hydroge or a ydroxyl group Z hydrogen or Y a linear branched alkinyl group containing at least 3 carbon atoms which ma optionally also be substituted by free or ally modified hydroxyl or an ethinyl a saturated or unsaturated and A the in the steroid and which may contain additional substituents in the molecule which are inert towards the reagents used according to the and in which the hydrogen atom in the the methyl group in the the in the may have the ised by subjecting a corresponding pound to a selective Grignard reaction the by means of in which Y denotes the group described above and denotes bromine and and subse uently optionally selectively any unsaturated bond present in optionally esterifying or etherifying other hydroxyl groups than 14 group which may be ifying groups which are present ting ether groups where denotes ally introducing a group in the by methods which are in themselves either by purely chemical routes or by biological routes using Method according to Claim 1 characterised by using as starting Method according to Claim 1 characterised by using as the starting Method according to Claims 1 to 3 characterised by the reaction being carried out with the hydropyranyl ether of magnesium Method according to Claims 1 to 4 characterised by the rignard reaction being carried out at about preferably at about 0 to Method according to Claims 1 to 3 characterised by the selective hydrogenation being carried out with Method according to Claims 1 to 3 and terised by the selective hydrogenation being carried out in a low preferably Method according to Claims 1 to 3 characterised by the subsequent introduction of a 1 group being carried by a chemical with the aid of Compounds formula low or hydrogen or a 2 hydrogen or linear o branched or group containing at least 3 atom which may optionall also be substituted by or functionally modified or an ethinyl a saturated unsaturated and the in the steroi and which may contain additional in cule which inert towards th reagents used to the and in whic the hydrogen atom in the methyl group in the insufficientOCRQuality
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DESC038399 | 1966-01-29 |
Publications (1)
Publication Number | Publication Date |
---|---|
IL27182A true IL27182A (en) | 1971-01-28 |
Family
ID=7434686
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL2718266A IL27182A (en) | 1966-01-29 | 1966-12-29 | Method for the preparation of 22-hydroxy-6-ketosteroids from 20-formyl-6-ketosteroids |
Country Status (12)
Country | Link |
---|---|
AT (1) | AT280491B (en) |
BE (1) | BE693275A (en) |
CH (1) | CH497404A (en) |
DE (1) | DE1593492A1 (en) |
DK (1) | DK114133B (en) |
ES (1) | ES336023A1 (en) |
FI (1) | FI43075B (en) |
FR (1) | FR1509563A (en) |
GB (1) | GB1172273A (en) |
IL (1) | IL27182A (en) |
NL (1) | NL6701321A (en) |
SE (1) | SE330883B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2275683A1 (en) | 1996-12-20 | 1998-07-02 | Frederik Christian Gronvald | Meiosis regulating compounds |
-
1966
- 1966-01-29 DE DE19661593492 patent/DE1593492A1/en active Pending
- 1966-12-29 IL IL2718266A patent/IL27182A/en unknown
-
1967
- 1967-01-05 DK DK7167A patent/DK114133B/en unknown
- 1967-01-16 GB GB213667A patent/GB1172273A/en not_active Expired
- 1967-01-16 CH CH57267A patent/CH497404A/en not_active IP Right Cessation
- 1967-01-24 ES ES336023A patent/ES336023A1/en not_active Expired
- 1967-01-27 BE BE693275D patent/BE693275A/xx unknown
- 1967-01-27 FI FI24867A patent/FI43075B/fi active
- 1967-01-27 FR FR92777A patent/FR1509563A/en not_active Expired
- 1967-01-27 AT AT81067A patent/AT280491B/en not_active IP Right Cessation
- 1967-01-27 NL NL6701321A patent/NL6701321A/xx unknown
- 1967-01-27 SE SE124667A patent/SE330883B/xx unknown
Also Published As
Publication number | Publication date |
---|---|
BE693275A (en) | 1967-07-27 |
NL6701321A (en) | 1967-07-31 |
FI43075B (en) | 1970-10-01 |
CH497404A (en) | 1970-10-15 |
ES336023A1 (en) | 1968-02-16 |
DE1593492A1 (en) | 1970-07-16 |
FR1509563A (en) | 1968-01-12 |
AT280491B (en) | 1970-04-10 |
GB1172273A (en) | 1969-11-26 |
SE330883B (en) | 1970-12-07 |
DK114133B (en) | 1969-06-02 |
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