DE1618918A1 - Epoxy steroids - Google Patents

Description

Sh ion ogi & Co., Ltd. Osaka, Japan

Ep oxys t er oi d e summary

Strongly antiestrogenic and myotropic 2 <x _t «K-Epoxy-S ^ -androstan-17-on- and 2 χ, 3 'X-Ep-oxy-5 v.-androstan-i7 / ^ - ol derivatives with 2 / - -r-alkyl groups in connection with or without * 17O <L-hydrocarbon groups, process for the production of these compounds and pharißsseutiscfa © means for ais HuBiaa = miä Tetsrinärraedisin "oil® such fsirbiseUmg & a as an active ingredient.,

Bio Eriiaäuag concerns © in © η @ ΐϊ @ class

Vsrf & brsn su ϋΐΣ? ®? Hsr-Sb © llimg land 'pha, ra & s © utisobe means for you- Hy.Diaa «and yot @? Iiäsr-iri @ iisia _r . c! is selelx® Yarfeiaämagsm as

concerns öis B ^ finching 2ot _P

9ν

BATH ORIGINAL

iw ι ν »

with 2 ··> -alkyl groups in combination with or without -17-X-hydrocarbon groups the general formula

R ^ Ο-Γ, Γ

ί Ί

_ J

(D

where R is an alkyl group with up to 3 carbon atoms and X is an oxygen atom or the group:

OR "

means in which R ¹ a hydrogen atom or a hydrocarbon group with up to 3 carbon atoms and R "a hydrogen atom» a hydrocarbon carboxyacyl group with up to 11 carbon atoms or the group

ORIGINAL

As examples of the alkyl group with up to 3 carbon atoms, which is defined by E, any straight-chain or branched saturated hydrocarbon groups may be mentioned, for example methyl, ethyl, propyl and isopropyl. Examples of the alkyl groups with up to 5 carbon atoms according to the definition of Y are any straight-chain or branched saturated hydrocarbon groups, e.g. butyl, isobutyl, tert-butyl, 1-methylpropyl, pentyl, isopentyl, 1-methylbutyl, 1-ethylpropyl, 2 , 2-dimethylpropyl and 2-methylbutyl in addition to the above-mentioned examples for the alkyl groups with up to 3 carbon atoms; Examples of the ^{hydrocarbon group defined by R 1} with up to 3 carbon atoms are any straight-chain or branched unsaturated hydrocarbon groups, for example vinyl, ethynyl, propenyl, isopropenyl and propynyl, in addition to those mentioned above. Examples of the alkyl groups with up to 3 carbon atoms. Examples of the cycloalkyl groups defined by η include cyclopentyl, cyclohexyl and cycloheptyl. Examples of the hydrocarbon carboxyacyl group with up to 11 carbon atoms, which is defined by R ″, are any straight-chain or branched, saturated or unsaturated aliphatic, cycloaliphatic or aromatic hydrocarbon carboxyacyl groups, for example Poriayl, acetyl, propionyl, butyryl, isobutyryl, valeryl, 2 -Methylbutyryl, trimethylacetyl, caproyl, oenanthoyl, caprinoyl, pelargonyl, capryl, undecanoyl, undecenoyl, cyclopentanopropionyl, cyclohexanecarbonyl, benzoyl and 3-phenylpropionyl.

The following is an example, but by no means exhaustive List of compounds according to the invention given: ■ ;.

109814/2173 ORIGINAL BATHROOM

2 or, 3 ·> -Epoxy-2 ^ -methyl-5 ·> -androstan-17-οη ·, 2 -λ, 3 ^r A-epoxy-2 j -methyl-5 ^ -androstan-1 lfi -ol, 2 <x, 3 <* - Epoxy-2 '? , 17 - ^ - dimethyl-5 cc-andros tan-17/3 -ol, 2 -χ, 3 oc-epoxy-2 ₄ 1 -methyl-17ix-ethyl-5 ^ -androstane-1 lf $ -ol,

2 -y, 3 '^ -Epoxy-2 ₍ ? -Methy 1-17' * - -vinyl-5 oc-androetan-17 / ^ -ol, 2 .x, 3-Χ -Epoxy-2.? -Methy 1-17 ^f ^ -äthinyl-5 ^ -androstan-17A -ol, 2 N., 3 ^ -Epoxy-2 _/ * -methyl-17 "* - -propyl-5 ^ -androstan-17 / i -ol, 2, -χ, 3 ** ■ -Epoxy-2 _: >'-methyl-17 · "> - -allyl-5" --androstane-17 / ^ - 01, 2 vx, 3 ^ "- epoxy-2 ^ i -methyl-17 ^'1 ^ -propynyl-5 oc-androstan-17 / ol, 2'X, 3?'"^ - Spoxy-2 ϊ -fnethyl-17 '^ -isopropyl-5-androstan-1 ^ iß -ol, 2 oc, 3'X-Epoxy-2 _/ -> -äthyl-Sol-androstan - ^ - on, · 2 -χ, 3 x-Epoxy-2 ^ j -äthyl-5 ^ -andro3tan-17Z ³ -ol, 2: x, 3 x-epoxy-2 i -ethyl-17 ¹ ^ -methyl-5 <x -androstane-1 7/3 -ol, 2 χ, 3> ^ - epoxy-2 '.? -17 ¹ ^ - -diathyl-5 ot -androetan-17 / * -ol, 2 oc, 3ά-epoxy-2, -3 -ethyl-Ho ^ -vinyl-5 <x-androstan-1 lß ~ ol _t

2 -JL, 3 ^ -epoxy-2 ^? -äthyl-17 ^<ot --äthinyl-5 oL-androatan-H / ^ - ol, 2 x, 3oc-Epoxy-2/2 -äthyl-17 ^ -propyl-5 <% - androstan-17 /? - ol , 2 - *, 3 oc-Epoxy-2/3 -propyl-5 o <-androatan-17-one, 2 ex, 3 o * .- Epoxy-2/3 -propyl-5 ' ^% -androstan-1 3 -ol, 2 Tc, 3> x-Epoxy-2 ß -propyl-17 et -methyl-5 oC-androstane-1 iß -ol, 2 cc, 3 ^ x -Ep oxy-2 ^ '-propyl-17 ot- -äthyl-5 ol -andros tan-1 7ft - ol, 2 -> c, 3 -x-epoxy-2/ ⁵ -propyl-T7c> - -äthinyl-5x-androa tan-1 iß -ol, 2'X, 3 3 - Epoxy-2/3 _t nx-dipropyl-S ^ -androatan-H / ^ - ol, 2 <x, 3 α -Epoxy-2 ^ -propyl-17 ^ - is opropyl- 5 o «.- andros tan-1 7 $ -ol,

2 «X _f 3 ^r x.-Epoxy-2 _/ / 3 -isopropyl-5ov-Endrostan-i7.^ -ol, 2 ol, 3" * - Epoxy-2/3 -iaopropyl-H ^ -methyl-S oc-androstan-17/ ³ ^ oI, 2 OC ₁ 3 ok-Epoxy-2./3 -isopropyl-17 ^ -äthinyl-5 c ^ -androstan-1 Iß -ol,

and their 1-alkoxycycloalkyl ethers, e.g. 1-methoxycyclopentyl ether, 1-ethoxycyclopentyl ether, 1-propoxycyolopentyl ether, 1-13opropoxycyclopentyl ether, 1-butoxycyclopentyl ether, 1-pentyloxycyclopentyl ether, 1-methoxycyclohexyl ether, 1-xthoxy-

1 ·

109814/2173

BATH ORIGINAL

cyclohexyl ether, I-isopropoxycyclohexyl ether, 1-tert-butoxycyclohexyl ether, 1- (1-methylpropoxy) cyclohexyl ether, 1- (1-methylbutoxy) cyclohexyl ether, 1-methoxycycloheptyl ether, I-ethoxycycloheptyl ether, 1-propoxycycloheptyl ether, 1-isobutoxycycloheptyl ether, I-isopentyloxycycloheptyl ether and 1- (2,2-Dimethylpropoxy) cycloheptyl ethers or their hydrocarbons carboxyacylate, e.g. formates, acetates, propionates, butyrates, isobutyrate, valerate, is ovalerate, 2-methylbutyrate, Trimethylaeetate, Caproate, Oenanthate, Caprylate, Pelargonate, Caprate, T-indecanoate, undecenoate, cyclopentane propionate, Cyclohexane carbonates, benzoates and 3-phenylpropionates ..

As far as it has been established so far, the compounds according to the invention have strong antiestrogenic activity, uierotropic activity and implantation delaying effect. They also show a strong myotropic effect, which is accompanied by a relatively weak androgenic effect, 2 ^ c , 5> x-epoxy-5ocandrostan-17 / ^ - ol has a low myotropic effect. The introduction of a methyl group in the 2-position leads to an increase in the effect of 15 times compared to the parent compound. It should be pointed out that the introduction of a methyl group in the 3-position of the same parent compound leads to a significant reduction in the same effect. The compounds according to the invention can therefore be used with advantage as myotropic or anabolic agents for the treatment of malnutrition, for promoting granulation formation or for the treatment of mastopathy and breast cancer and the like.

The compounds of the formula I given above can be obtained from the corresponding 5ac-androst-2 »enes of the formula

109814/2173

BATH ORIGINAL

_ 5 -

(ID

where R and X are as defined above. Examples of this are in the following, by no means exhaustive List given:

2-methyl-5 ^{: x} --andro3t-2-en-17-one _t 2-methyl-5 - · * ■ -androe t-2-en-T7./S -öl, 2.17 «> - Dimethyl-Sot-androst - ^ - en - ^ / S-oil, 2-methyl-17 ^ -äthyl-5 "- androst-2-en-17/5-oil,

2-methyl-17 ¹ ^ - vinyl-5 οί — androst-2-en-17 / S-ol,

2-Me thy 1-17 oc -äthinyl-5 o ^ androat-2-en-1 l _f ß -öl,

2-Me thy 1-17 *. ~ propyl-5 '> - androat-2-en-17 / ^ - ol ,.

2-methyl-17 ". -propinyl-5 ^ -androst-2-en-1 Ί & oil, 2-methyl-17-X.-i3opropyl-5CC-andro3t-2-en-17/3-ol 2-ethyl-5 ⁰ ^ -androst -2-en-17-one, 2-ethyl-5 · * -andro "8t-2-en-1 1 ^ -öl _f

2.17 ry. -Diäthyl-5 -x -androate-2-en-17, ^ -öl, 2-ethyl-17 ^ -vinyl-5 '^ - androate-2-en- 1Iß -öl , 2-Äthy 1-17> x-äthinyl-5oc-anaroet-2-en-i 7Z ⁹ -öl, 2-Xthy 1 ^ -17 c ^ -propyl-5oc-androet-2 ~ en-17/3-ol, 2-propyl-5 it --androst-2-en-17-on »

T098U / 2173

BATH ORIGINAL

2-? Ropyl-5 & ~ -androst-2-en-i I ^ -ol,
2-propyl-17 ^t * - methyl-5'S - androst-en-2-17/3-ol, 2-propyl-17 ^'x --äthyl-5 ^ androst-2-e9-17 ^/? -ol, 2 _T propyl-17- ^J -äthinyl-5 ^ -androst ~ 2 ^ n-17 /? -ol, 2.17 -χ. -Dipropyl-5X-androst-2-en-17 /> - ol, '2 ~ Propyl-17 ^ ^v -isopropyl-5 "^ -androst ^ -en - ^ /? -Ol, 2-isopropyl-5 ^i3C -androst-2-en-17/3-ol, 2-isopropyl-17 <x -raethyl-5OL

2-isopropyl-17 ^c * - ethinyl-5 ⁱ '> - androst-2-en-17 _/ / 3 -ol

and their corresponding 1-Alkoxycycloalkyläthe.r or hydrocarbon carboxyacylate as mentioned above.

According to the process of the invention for "preparing the compounds I becomes one of the starting compounds II with an organic peracid, e.g. performic acid, peracetic acid, Perpionic acid, perbutyric acid, trifluoroperacetic acid, monosuccinic acid, Percamphoric acid, perbenzoic acid, monoperphthalic acid, Diperterephthalic acid, p-nitroperbenzoic acid or m-chloroperbenzoic acid, in an inert organic solvent, e.g. Benzene, Kethylene Chloride, Chloroform, JLther, Dioxane, Acetone, acetic acid or acetonitrile treated. The reaction can be carried out at temperatures in the range of about -15 bia 100 ° C carried out for a period of 30 minutes to 100 hours will. The reaction products can be isolated and purified in the usual way outside the reaction. If if desired, the products in the context of general formula I can be converted into one another.

If the product consists of a 2β- substituted 2θς, 3τ \ - Bpoxy-5 ^ - androstan-17-one, it can lead to the corresponding 2β -substituted 2. ^, 3 ,, vEpoxy-Soc-androstan-17 / 5-ol

109814/2173

BATH ORIGINAL

by treatment with a metal-containing reducing agent, e.g. lithium tri- (tert-butoxy) aluminum hydride, in a suitable organic solvent reduced in the usual way or into the corresponding 1? X-hydrocarbon-substituted Derivative by treatment with a hydrocarbon magnesium bromide or a hydrocarbon lithium compound or an alkyne which, according to the definition of R · up to Have 3 carbon atoms, in the usual way, the general referred to as the Grignard reaction. If the product is a 2/3 substituted 2 oc, 3 cv-epoxy-5 "/ - androstane-17i-oil with or without a 17'X hydrocarbon substituent is, it can be converted into the corresponding hydrocarbon carboxyacylate, as mentioned above the usual acylation procedure using conventional acylating agents, e.g., acid anhydrides or acid halides in the presence of a base, e.g. fyridine, or converted to the corresponding 17 /> -O-Alkoxycycloalkylether) Action of the corresponding alkylenol or dialkyl ketal of cycloalkanones

YO

YO C ^ (-CH ₂ L ₁ or

wherein Y and η are as defined above, in the presence of one Acid catalyst can be etherified as usual. If the product is gin 2 / ^ - substituted 2 X, 3 c * .- epoxy-5o ^ -androstane-17 /? oil is without a 173c substituent, it can be converted into the corresponding 17-one by using the usual oxidation process converted by chromium trioxide in a basic medium such as pyridine will. If the product is a 17-acyl derivative of '

1098U / 2173

BATH ORIGINAL

- Q -

2 / -substituted 2 -χ-, 3 ·> -Epoxy-5 .X-androstane-17> -öl rait or without a 17 x substituent, it can be converted into the corresponding free 17:, 7-ol compounds by common alkaline Hydrolysis, e.g. converted by the action of potassium carbonate or potassium hydroxide in a suitable solvent will. If the product is in position 17 ^ - by an unsaturated Hydrocarbon substituted derivative of 2 j -substituted 2λ, 3 ■> -Epoxy-5 - ^ - androstane-i7 / 2 -oil, it can lead to the corresponding dihydro or tetrahydro derivative, e.g. to a 17-y-alkenyl or -alkyl compound the usual catalytic ^ reduction process are hydrogenated.

The compounds according to the invention are used in human or veterinary medicine alone or in combination or as a preparation in conjunction with a solid or liquid pharmaceutical diluent. The preparations are produced by known methods, for example using pharmaceutical organic or inorganic diluents that are suitable for enteral or parenteral administration.Suitable diluents are substances that do not react with products according to the invention, e.g. water, vegetable oils, benzyl alcohol, polyethylene glycols, gelatin , Lactose, starches, magnesium stearate, talc, white petrolatum, isopropyl myristate, or other known pharmaceutical diluents or carriers. Preparations for parenteral administration, preferably as solutions, for example oily or aqueous solutions, suspensions, emulsions, granules, tablets or implants, are produced therefrom. Similar preparation forms are used purely enterally, which can also contain other therapeutically active substances. The content of the active compounds in these preparations, e.g. in an ampoule, is

109814/2173

BATH ORIGINAL

- ίο -

preferably carries 100% to 500 mg or 1 part per million to 50 % or, in the case of tablets, preferably 1 mg to 250 mg.

The invention is further illustrated by the following examples.

example 1

A solution of 1.935 g of 2-methyl-5 ^ f-androst-2-en-17 ^ -01-acetate (£ .J. Ringold et al .; J. Am. Chem. Soc., 81_, 427 (1959 ) in a mixture of 20 ml of methylene chloride and 20 ml of ether is mixed with 15 ml of monoperphthalic acid in ether (109 mg "/ ml) and left to stand overnight at 0 ° C. The reaction mixture is washed with aqueous sodium carbonate solution, dried over anhydrous sodium sulfate and removed from the The residue is recrystallized from acetone, whereby 1.601 g of 2 ·> -, 3 ^ -epoxy-2 /? -Methyl-5-oc-androstane-17 /? - ol acetate, P. 208-210 ° C obtained. [* J24 _{m + 10f} gO ( _c ■, _{1> O73 in} chloroform).

Example 2

804 mg 2 ** -, 3 ° ^ -Epoxy-2 /? Methyl 5 x androstane-1 3 -ol acetate, which was prepared according to the method described in Example 1, is dissolved in 50 ml of methanol, and 800 mg of potassium carbonate in 6 ml of water are added. The resulting mixture is refluxed for 4 hours, diluted with water and extracted with methylene chloride. The extract solution is washed with water, dried and evaporated. By recrystallizing the residue from a mixture of acetone and hexane, 626 mg of 2, · .χ, 3ίΧ-epoxy-2 / i-raethyl-5o <- androstane-17/3 -öl, mp 184-185 ° Q are obtained ,

⁴ "'+ 21, O ⁰ (c >> 1.013 in chlorine form).

109814/2173

BATH ORIGINAL

Example 5

A solution of 432 mg of 2 -v., 3 -X-epoxy-2 i-methyl-5-androstane-17 'VoI in 2 ml of pyridine is mixed with 0.5 ml of propionic anhydride and the resulting mixture is at Left to stand at room temperature. The reaction mixture is diluted with ice-cold water and the crystals formed are filtered off. Recrystallization from methanol gives 498 mg of 2 -x, 3ct-Epo? Y-2 '--methyl-5 - ^ - androstane-17 / ^<:? - Obtain ol propionate. IS: ^!? ^ ⁰¹ 1734, 1239 cm "" ¹ .

In the same way, 2- * L, 3> - epoxy-2 / ^ -methyl-5o <-androstan-

17 / 3-01 into the corresponding acylates, valerate, isovalerate, Enanthate and caprylate by reaction with more than equimolar amounts of valeric anhydride, isovaleric anhydride, Gnanthic anhydride or caprylic anhydride converted in the presence of pyridine.

"Example 4 ■

A solution prepared by mixing 1 g of chromium trioxide and 25 ml of pyridine with external cooling with ice is treated at the same temperature with 1 g of 2 ri, 3 o.-epoxy-2 / ^I-methyl-5> -xandrostan-17 5 ~ ol in 20 ml of pyridine are added, the mixture obtained is stirred for 1 hour and left to stand overnight at room temperature. The reaction mixture is diluted with ice water and extracted with chloroform. The extract solution is washed with water, dilute hydrochloric acid, dilute sodium carbonate solution and water in this order and then evaporated. The residue is chrcTnatographiert on neutral aluminum oxide and eluted with petroleum ether / benzene ^ - _t .Fraktion from methanol 'u 2'>. _t 3.> .- Epoxy-2 _/ / 3-methyl-5c <- * androstan-17-one recrystallized. F = 173-177 ° C.

1G98U / 2173

BATH ORIGINAL

B e i s ρ i - β 1 5

A solution of 1.502 g of 2 »methyl-5oL-androst-2-en-17/3-oil in a mixture of 20 ml of methylene chloride and 20 ml of ether is mixed with 15 ml of monoperphthalic acid in ether (109 mg / mg) and overnight left to stand at 0 ° C. By working up the reaction mixture as in Example 1, 1.231 mg of 2x., 3 '* - epoxy-2 / ^? -methyl-5 x-androstan-17 / s-ol vom P. = 184-186 ° C (from a mixture of acetone and hexane).

At 3 ρ 4 e 1 6

A suspension of 560 mg 2 -: x, 3o ^ -Epoxy ~ 2? -methyl-5 -χ- ~ ol i © 5 ml of tert-butanol is mixed with 1 ml of cyclopenta

nonenolmethylättier and 10 mg of p-toluenesulfonic acid pyridißealz added. The mixture obtained is stirred for 4 hours at room temperature and poured into a dilute aqueous sodium carbonate solution. The mixture is extracted with methylene chloride and the extract obtained is worked up as usual to give 6-6 mg of crude product, which is 543 mg * Λίβ - when chromatographed on aluminum oxide. (1-methoxy-1-cyclopentyloxy) «2 <x, 3tt, - /

epoxy-2/3 -aethyl-5ά-andfostan supplies, P. * 123-125 ° C.

Amf @ loading the procedure described above on Oyclohexanonenolmethyläther one obtains 17 / ^ - (1-Methoxycyclohexyloxy) -2 ^r JC, 3-X-epoxy-2 _/ / ü ^> -methyl-5 <x -androstane, which at °

153 * 155 ° C melts.

B e i 8 ρ i β 1 7

A solution of 2.010 g of 2,17oC-dimethyl-5:> - androst-2-en-17 ·. ^ * ol in a mixture of 20 ml dichloromethane and 20 ml ether is mixed with 16 ral monoperphthalic acid in ether (109 mg / ml)

U / 2173

BATH

sets and left to stand overnight at 0 ° C. The reaction mixture is washed with aqueous sodium carbonate, over; Dried sodium sulfate and freed from solvent. Recrystallization of the residue from acetone gives 1.557 g of 2 'v, 3' ^ - epoxy-2. ", 17 x.-dimethyl-5.χ.-androstane-1.7A oil. ^: . ■■ -,

Example 8 . - -.

Sine solution of 1.00 g of a-Hethyl-i ^^ - äthinyl-Soc-androst-a-en-17 "oil in a mixture of 8 ml dichloromethane and 8 ml Ether becomes with 8 ml monoperphthalic acid in ether. (1Ό9 mg / mg) added and left to stand overnight at 0 ° C. * The reaction mixture is washed with aqueous sodium carbonate solution, dried over anhydrous sodium sulfate and freed from solvent. The residue is recrystallized from acetone and returns 0 * 965 g 2

i7 - ^ - ethinyl-5 ^ -androstane-17 " ^J '~ ol ₀ P, = 175-177 °

example

In 30 ml of a mixture of tetrahydrofuran and ether (2: 1) dry acetylene gas is introduced for 1 hour. The solution is anhydrous with a solution of 1.5 g of potassium metal in 10 ml Amyl alcohol is added., While stirring, 1.350 g, 2 ·> -, 3 · ^ -Epoxy-2 / '? - methyl-5'X-andres tan-17-one in 20 ml of a Mixture of tetrahydrofuran and ether (1i1) dropwise added to the above mixture within 30 minutes, while acetylene gas is being introduced. After 3 hours Aqueous ammonium chloride solution is added to the passage and introduction of acetylene gas. The mixture obtained is extracted with ether and washes the extract with water "aqueous sodium" carbonate solution and water in that order, dries over

109814/2173

BATH ORIGINAL

anhydrous sodium sulfate and evaporated. The residue is "uaikristaliisiert" from a mixture of methylene chloride and methanol and gives 1.280 g 2 ^ _? 3 ⁱ * - lpoxy-2 /? - methyl-T7 /> ⁵ -> äthinyl-5 '* - androstane-17.- J ~ ol. F. = 175-177 ° C. ",

Ex iel 10

A suspension of 400 mg Lindler catalyst in 10 ml ethyl acetate is mixed with a solution of 409 mg 2 ^, 3 *> - / 2 methyl-17 '' ⁵ ^ -ethihyl-5 ^ -androstan-17 /> - ol in a mixture of 5 ml of ether and 10 ml of ethyl acetate. The hybrid obtained is hydrogenated. After 15 minutes, the reaction mixture is filtered to remove the catalyst and the filtrate is evaporated. Recrystallization of the residue from a mixture of methylene chloride and methanol gives 356 mg of 2 '.x., 3' * .- E'poxy-2 "/ '- mettayl-17 x-vinyl-S ^ -androstan-17 / 5-01. P. = -82-88 ° C. ·

Be is ρ ie _n l _ii -11

300 mg of 10 io palladium-calcium carbonate catalyst are hydrogenated in 10 ml of ethyl acetate. This mixture is .with a suspension of 136 mg 2 o <-, 3 ⁱ x ~ epoxy- »2: ^/? -isethyl-17ot - «> äthinyl-5 ^ ..- anärostan-17 / -> - oil in 25 ml Äthylace'tat and the resulting mixture is hydrogenated at room temperature for 15 minutes. By working up the reaction mixture as in Example 10, 98 mg ^ - ^, Joc-Epoxy ^ / ^ are obtained
androstan-17 - ^ - ol, P. - 129-131 ° C.

109814/2173

BAD ORfGINAL

Claims (13)

a -ta η ta η s ν r Ü e ^: he t, - A compound'dei * formula where R is an alkyl group with up to "3 Uolilenst off atoms and % an oxygen atom or the like?" means «in the 1 * © in.
Hydrogen group with up to 3 carbon atoms. "-" ntf R "a hydrogen atom, 'a hydrocarbon carboxyacyl group with up to 11 carbon atoms or the same group where Y is an alkyl group with> is at 5 carbon- imä η an integer of . $ to '6 means. Unierlöden TOSS U / $ 217 BAD ORiQIWAL 2. 2 oc, j <x-Spoxy-2 /? -methyl-5 * -androstan-J7-one. 3. 2 ^ x-, 3o <- epoxy-2/3-methyl ^^ - androstan-t? / * - ol, 4 x 2 ^, 3 ^ -epoxy-2 / "? -Methy 1-5 ** -androstane-1 Ip -ol-lower alkanoate. 5. 2 ^ -, 3 oL-epoxy-2 / »-methyl-5 ^ - -androstane-17/3 -ol-acetate. 6. 2-χ., 3 oc-epoxy-2 ^ -methyl-5O ^ -andrestan-1 7-'3 -ol-propionate. 7. 2-v, 3.x.-epoxy-2 / '3 -methyl-5 ° "- androstane-1? /' ⁵ -ol-valerate. 8. 2-y- , 3 ^ -epoxy-2. · ^ -Methyl-5 ^ - -androstane-17/3 · -ol-isovalerate. / i 9.2 m, 3 ^ -epoxy-2 / ^ -methyl-5 ^ -androstane-17/ ¹ ^ -öl-oenänthat. 10. 2 -ν., 3 ^: > -Epoxy-2/3 -methyl-5 cx-androstane-i 7/3 -ol-caprylate. 11. 17y ³ - (I-Mettioxy-1 -cyclopentyloxy) -2 O ^, 3 oc-epoxy-2 /? -methyl-5 <"x - andr os t an. 12. 2 <~ * _f 3 ^t > - epoxy-2 / ^? -17o ^ -dimethyl-5ot ⁵ -androstane-17/ ⁵ -oil. 13- 2 Oc, ^{3-.x-epoxy-2/3-methyl-17oc-ethynyl-5-androstan-17} ex / ^s' fish oil, 14 "'2 nt, 3' ^ - epoxy-2 / ^ -methyl-17o ^ -viny 1-5 ^ -androstane-1 TV ^ -öl '. 15. 2 -y, .3c: x - epoxy-2/3-methy 1-17 "- -ethyl-sol-androstane-177 ^s -ol. 109.8U / 2173 BAP ORIGINAL ", 16. Process for the preparation of compounds of the "formula ■ ■ "- ■ - '. Χ wherein R is an alkyl group with "up to 3 carbon atoms and X is an oxygen atom or the group means in which R ^{r is} a hydrogen atom or a hydrocarbon group with up to 3 carbon atoms and R "is a hydrogen atom, a hydrocarbon carboxyacyl group with up to 1t carbon atoms or the group is, v / obei Y is an alkyl group with up to 5 carbon atoms and η means a whole number from 4 to 6, thereby characterized in that there is a * compound of the formula 109814/2173 BATHROOM OFÜ0IP4AL - 13 - wherein R ⁴¹ UnCi X are as defined above, treated with an organic peracid in an inert organic solvent and, if appropriate, then one or more of the following measures known per se applies: Treatment with a metal-containing reducing agent in an organic solvent, Treatment with a hydrocarbon magnesium bromide or a hydrocarbon lithium compound or an alkyne, which have up to 3 carbon atoms, Treatment with a conventional acylating agent in the presence a base, Treatment with the corresponding Alkyle'nol or Dialkylketal of the cycloalkanone in the presence of an 'acid catalyst, Use of a common oxidation process, Use of the usual alkaline hydrolysis and use of a catalytic reduction process. 109814/2173 BATH ORIGINAL Ib ftf3J8 17. The method according to claim 16 .. characterized in that the reaction is carried out at temperatures in the range of about -15 to 3 10 ° C for a period of 30 minutes 100 hours. 13. Means for human or veterinary medicine, marked by one or more of the compounds according to claim. 109814/2173 BAD ORIgINAt