CH507902A - N-Subst 9-aminoalkyl-9,10-dihydro-9,10-ethano-anthracene derivs - Google Patents

Abstract

(A) N-substd. 9-(aminoalkyl) 9,10-dihydro 9,10-ethano-anthracenes with the nucleus of formula (I) contng. a free- or acylated hydroxyl- or oxo group at pos. 12. The alkylene residue of the N-substd. aminoalkyl at pos. 9 is pref. a linear- or branched alkylene (C1-4). The amino group may be sec. or tert. and is pref. aliphatic such as an aliphatic hydrocarbon (max C8) opt. contng. hetero-atoms in the chain. They may be further substd. at pos. 1-8 with alkyl (max C6), alkoxy (max C8), halogen, trifluoromethyl and/or nitro; pref. not more than 2 substituents each at pos. 1-4 and 5-8. Pos. 11 or 12 may be substd. with alkyl, pref. methyl. Preferred cpds. (I) have general formulae: R = H or alkanoyl Alk = alkylene (C1-3), pref. (CH2)n; n = 1, 2 or 3 Ro = mono- or dialkylamino, benzylamino, an opt. beta-monounsatd.- and/or C-alkylated morpholino, thiomorpholino-, piperazino-, N'-alkylpiperazino- or N'-(hydroxyalkyl)-piperazino group. R1 and R2 may be same or different alkyl, alkoxy, halogen, nitro or pref. H. (B) Acid addition salts of (I) with organic- and inorganic acids.

Description

  

  
 



   Process for the preparation of N-substituted 9- (aminoalkyl) -9,10-dihydro-9910-ethano-anthraceles
The invention relates to a process for the preparation of N-substituted 9- (aminoalkyl) -9,10 dihydro-9, 10-ethano-anthracenes having the core of the formula
EMI1.1
 which have a hydroxyl group or an oxo group in the 12-position, and their salts.



   The N-substituted aminoalkyl radical in the 9-position is preferably an N-substituted amino lower alkyl radical, in which the alkylene radical connecting the substituted amino group to the anthracene nucleus is above all a lower straight or branched alkylene radical having preferably 1 to 4 carbon atoms, such as. B. the methylene, ithylen- (1,2) -, ethylidene, propylene (1,2) -, propylene (1,3) -, propylidene, butylidene, butylene (1,2) - , Butylene (1,3), butylene (2,3) or butylene (1,4) radical.



   The amino group of the N-substituted aminoalkyl radical can be secondary or tertiary, preferably it is an aliphatic amino group, i. H. an amino group mono- or disubstituted by residues of aliphatic character. The term radicals of aliphatic character refers to those radicals whose first carbon atom, which is connected to the nitrogen atom, is not a member of an aromatic system.

  As substituents of a secondary or terbiary amino group, for example, are therefore to be mentioned: lower hydrocarbon radicals of aliphatic character, which are also interrupted by heteroatoms, such as oxygen, sulfur or nitrogen atoms, in the carbon chain and / or, e.g. B. can be substituted by hydroxyl groups. Lower hydrocarbon radicals of aliphatic character as substituents of the amino groups are above all alkyl, alkenyl, alkylene, A + alkynyl, cycloalkyl, cycloalkenyl, cycloalkyl-alkyl or -alkenyl radicals or cycloalkenyl-alkyl or -alkenyl radicals with a maximum of 8 carbon atoms or aralkyl or aralkenyl radicals, such as e.g. B.

  Phenyl lower alkyl or alkenyl radicals, e.g. B. a benzyl, phenylethyl or cinnamyl radical, which also, for. B. by lower alkyl radicals, lower alkoxy groups, halogen atoms, Triflluorome- thylgiuppen and / or nitro groups, can be substituted. Residues of this type interrupted by heteroatoms are primarily oxaalkyl, oxaalkylene, azaalkylene or thiaalkylene radicals.

  Mention may be made as substituents of the amino group in particular methyl, ethyl, allyl, propyl, isopropyl, methallyl, propargyl, straight or branched butyl, pentyl, hexyl or heptyl radicals connected at any point, 3 -Oxabutyl-, 3-oxapentyl-, 3-oxaheptyl-, 2-hydroxyethyl-, 3-hydroxypropyl-, butylene- (1,4) -, pentylene- (1,5) -, hexylene- (1,5) - , Hexylene (1.6), hexylene (2.5), heptylene (1.7), heptylene (2.7), heptylene (2.6), 3-oxapentylene (1,5) -, 3-thiapentylene- (1,5) -, 2,4-dimethyl-3-thiapentylene- (1,5) -, 3-aza-pentylene- (1,5) -, 3-lower alkyl -3-aza-pentylene (1,5) -, such as 3-methyl-3-aza-pentylene- (1,5) -, 3- (hydroxy-lower alkyl) -3-azapentylene- (1,5) -, such as 3 - (ss-Hydroxyethyl) -3-aza-pentylene- (1,5) -, 3-oxahexylene- (1,6) - or 3-azahexylene- (1,6) radicals, optionally lower alkylated,

   such as methylated, cyclopropyl, cyclopentyl or cyclohexyl radicals or cyelopropyl, cyclopentyl or cyclohexylmethyl or ethyl radicals.



   The substituted amino group is above all a mono- or di-lower alkylamino group, such as methyl, ithyl, propyl, butyl, isopropyl, sec-butyl, dimethyl, diethyl, N-methyl-N-ethyl, Dipropyl, diisopropyl, dibutyl, di-sec-butyl or di-amylamino group or an optionally C-lower alkylated and / or in the ring ss-monounsaturated pyrrololidino or piperidino group or an optionally C-lower alkylated piperazino, N'-lower alkyl or N '- (hydroxy-lower alkyl) -piperazino, thiomorpholino or morpholino group.



   The new compounds can contain further substituents.



   For example, they can contain lower alkyl radicals, lower alkoxy groups, halogen atoms, trifluoromethyl groups and X or nitro groups on the aromatic rings (positions 1-8). Each of the two cores (positions 1 to 4 and 5 to 8) advantageously has no more than two, preferably at most one, of the named substitutes.



   Furthermore, the new compounds can be substituted in one of the 11 or 12 positions. Lower alkyl radicals, in particular methyl radicals, are particularly suitable as sulpho substituents.



   A lower alkyl radical on one carbon atom is in particular an alkyl radical having at most 6 carbon atoms, such as. B. a methyl, ethyl, propyl or isopropyl radical or a straight or branched butyl, pentyl or hexyl radical connected in any position.



   Lower alkoxy groups are especially those with a maximum of 6 carbon atoms, such as. B. methoxy, ethoxy, propoxy, isopropoxy or butoxy groups and the halogen atoms are especially fluorine, chlorine or bromine atoms.



   The new compounds have valuable pharmacological properties, in particular a psychotropic effect. Thus, as shown in animal experiments, e.g. in mice given orally at doses of 30 to 100 mg / kg shows an inhibition of the mescaline-generated psycbomotor excitation. The new compounds can therefore be used as psychotropic drugs. However, the new compounds are also valuable intermediates for the production of other useful substances, in particular pharmacologically active compounds.



   Particularly noteworthy are the compounds of the formula
EMI2.1
 as well as the compounds of the formula
EMI2.2
 wherein aik is a lower alkylene radical having 1 to 3 carbon atoms, especially the radical of the formula - (CH2) n-, wherein n is 1, 2 or 3, R "is a mono- or di-lower alkylene group, especially a mono - Or dimethylamino group, a benzylamino group, a piperidino or pyrrolidino group which is optionally unsaturated and / or C-lower alkylated in the ring, or an optionally C lower alkylated morpholino, thiomorpholino, piperazino, N 'lower alkylpiperazino or N'- (Hydroxy-lower alkyl) piperazino group,

   such as N'-methyl or N '- (ss-hydroxy-ethyl) -piperazino group, and R1 and R2, which can be the same or different, lower alkyl groups, lower alkoxy groups, especially methoxy, halogen atoms, especially chlorine, nitro groups or are preferably hydrogen atoms, and in particular the 9 - (γ-dimethylaminopropyl) -1 2-oxo-9, 1 O-dihydro-9,10-ethanoanthracene, the 9 - (γ-methylaminopropyl) -
12-oxo-9,10-dihydro-9,10-ethanoanthracene.



   The process according to the invention for the preparation of the new compounds is characterized in that in a 9,10-dihydro-9,10-ethano-anthracene that has an acyloxy group in the 12-position and an N-substituted amino alkyl radical in the 9-position, or in a salt thereof, the acyloxy group is reduced to the hydroxyl group.



   An acyloxy group is primarily one formed by carboxylic acid residues, e.g. aliphatic or aromatic carboxylic acid residues, substituted hydroxyl groups, e.g. a hydroxyl group esterified by benzoic acids, such as the benzoyloxy group, or in particular a lower alkanoyloxy group, especially one with at most 6 carbon atoms, such as a propionyloxy, butyryloxy, caproyloxy or especially an acetoxy group.



   The reduction to the free hydroxyl group can be carried out in a conventional manner, e.g. B. with an ester reducing agent such as sodium in a lower alkanol, a Dileichtmetallhydrid such as lithin maluminou m- hydride, or catalytically in the presence of a suitable catalyst such as a copper chromite catalyst.



   In the compounds obtained, the hydroxyl groups in the 12-position to the oxo group can be oxidized.



   The oxidation can be carried out in the usual way, for example by treatment with oxidizing agents, e.g. B. chromium (VI) compounds such as chromic acid or chromium trioxide / pyridine, hypohalites such as tert-butyl hypochlorite, copper (II) salts, e.g. B.

  Copper sulfate, bismuth oxide, or, for example, according to the Oppenauer method, e.g. by treating with ketones such as lower alkanones, e.g. Acetone, cycloa canons such as cyclohexanone, or quinones in the presence of suitable catalysts such as metal salts. in particular aluminum salts, of branched lower alkanols such as aluminum tert-butylate or aluminum isopropylate, or aluminum phenolates.

 

   In the compounds obtained, substituents can be introduced, modified or split off within the scope of the end products.



   Thus, for example, in compounds in which the amino group of the aminoalkyl group is a secondary amino group or an N′-unsubstituted piperazino group, these radicals of aliphatic character can be introduced. This is done by reacting with a reactive ester of a corresponding alcohol or an epoxy.



     Reactive esters are primarily esters with strong inorganic or organic acids, preferably with hydrohalic acids such as chloric, bromic or hydroiodic acid, with sulfuric acid, or with arylsulfonic acids such as benzene, p-bromobenzene or p-toluenesulfonic acid.



   These subsequent conversions can be carried out individually or in combination and in any order.



   Depending on the process conditions and starting materials, the end products are obtained in free form or in the form of their salts, which is also included in the invention. The salts of the end products can be used in a manner known per se, e.g. be converted into the free bases with alkalis or ion exchangers.

  Of the latter, salts can be obtained by reaction with organic or inorganic acids, in particular those which are suitable for the formation of therapeutically useful salts. Examples of such acids are:

  Hydrogen halides, sulfuric acids, phosphoric acids, nitric acid, aliphatic, alicyclic, aromatic or heterocyclic carbonic or sulfonic acids, such as formic, acetic, propionic, succinic, glycolic, lactic, apple, tartaric, lemon, ascorbic acids , Maleic, hydroxyrnalein or pyruvic acid; Phenyl acetic, benzoic, p-amilnobenzoe, antbranil, p-hydroxy-benzoic, salicylic or p-aminosalicylic acid, emboxylic acid, methanesulphonic, ethanesulphonic, hydroxyethanesulphonic, ethylene sulphonic acid;

  Halobenzenesulfonic, toluenesulfonic, naphthalenesulfonic acid or sulfanilic acid; Methionine, tryptophan, lysine or arginine.



   These or other salts of the new compounds, such as. B. the picrates or perchlorates, can also be used to purify the free bases obtained by converting the free bases into salts, separating them and in turn frees the bases from the salts. As a result of the close relationships between the compounds in free form and in the form of their salts, in the preceding and in the following the free bases are to be understood appropriately and appropriately, if appropriate also the corresponding salts.



   The invention also relates to those embodiments of the process according to which one starts from a compound obtainable as an intermediate product at any stage of the process and carries out the missing process steps, or in which a starting material is formed under the reaction conditions, or in which a reaction component is given. if present in the form of their salts.



   The new compounds, provided they have asymmetric carbon atoms, e.g. B. in the aminoalkyl radical or at another location, and depending on the choice of starting materials and working methods, as optical antipodes or racemates or, provided they contain at least 2 asymmetric carbon atoms, as isomer mixtures (racemic mixtures).



   Mixtures of isomers (mixtures of racemates) obtained can be separated into the stereoisomeric (diastereomeric) pure racemates in a known manner on the basis of the physico-chemical differences between the constituents, for example by chromatography and / or fractional crystallization.



   Racemates obtained can be obtained by known methods, for example by recrystallization from an optically active solvent, with the aid of microorganisms, or by reaction with an optically active acid which forms salts with the racemic compound and separation of the salts obtained in this way, e.g. B. due to their different solubilities, decompose into the diastereomers, from which the antipodes can be released by the action of suitable agents. Optically active acids commonly used are e.g. B. the D- and L-forms of tartaric acid, di-o-toluyltartaric acid, malic acid, mandelic acid, camphorsulfonic acid or quinic acid. It is advantageous to isolate the more effective of the two antipodes.



   For carrying out the reactions according to the invention, it is expedient to use those starting materials which lead to the groups of end materials particularly mentioned at the beginning and especially to the end materials specifically described or emphasized.



   The starting materials are known or, if they are new, can also be obtained by methods known per se, e.g. B. as described in the examples.



   The new compounds can e.g. in the form of pharmaceutical preparations which can be used in free form or optionally in the form of their salts, especially the therapeutically usable acid addition salts, mixed with a z. B. for enteral, e.g. B. oral or parenteral administration suitable pharmaceutical organic or inorganic, solid or liquid carrier material.



   The new compounds can also be used in veterinary medicine, e.g. B. in one of the forms mentioned above or in the form of feed or additives for animal feed.



   In the following examples the temperatures are given in degrees Celsius.



   example 1
A solution of 12 g of 9- (dimethylaminoinethyl) -12-acetoxy-9,10-dihydro-9,10-ethano-anthracene in 100 ml of absolute tetrahydrofuran is added dropwise with stirring to 5 g of lithium aluminum hydride in 75 ml of tetrahydrofuran. The reaction mixture is stirred for one hour at 50 and then decomposed at 10 by adding 5 ml of water, 5 ml of 15% sodium hydroxide solution and another 15 ml of water. The precipitate which has fallen out is filtered off, and the filtrate is evaporated in vacuo.

  The residue is crystallized from ethanol, and 9- (dimethylaminomethyl) -12-hydroxy-9,10-dihydro-9,10-ethano-anthracene of the formula is obtained
EMI3.1
 in crystals from F. 150-154. The methanesulfonate melts at 213-214.



   The following compounds can be prepared in an analogous manner: a) 9- (ethylaminomethyl) -12-hydroxy-9,10-dihydro
9,10-ethano-anthracene, F. 142, F. des Hydrochlorids 246, b) 9- (diethylaminomethyl) -12-hydroxy-9,10-dihydro-9,10-ethano-anthracene, F. 114-116,
F. des hydrochloride 239-240 ^, c) 9- (benzylaminomethyl) -12-hydroxy-9,10 dihydro-9,10-ethano-anthracene, F. 120-121,
F. des hydrochloride 278-279, d) 9 - (γ-methylaminopropyl) -12-hydroxy-9,10-dihydro-9,10-ethano-anthracene, F. 132-135,
F. des methanesulfonate 168-170, e) 9 - (γ-dimethylaminopropyl) -12-hydroxy-9,10-dihydro-9,10-ethano-anthracene hydrochloride, f) 9 - [γ;

  ;-( N '- [ss-hydroxyethyl] piperazino) - propyl] - 2-hydroxy-9, 1 0-dihydro-
9,10-ethano-anthracene dihydrochloride, g) 9- (γ-morpholinopropyl) -12-hydroxy-9,10-dihydro-9,10-ethano-anthracene-methanesulfonate, h) 9- (γ-pyrrolidinopropyl ) - 1 2-hydroxy-9, 10-dihydro-9, 10-ethano-anthracene, i) 9 - (γ-piperidinopropyl) -12-hydroxy-9,10-dihydro-9,10-ethano-anthracene methanesulfonate, k) 9- (cyclopropylaminomethyl) -12-hydroxy
9,10-dihydro-9,10-ethano-anthracene, l) 9-dimethylaminomethyl) -12-methyl-12-hydroxy
9,10-dihydro-9,10-ethano-anthracene and m) 2,6-dichloro-9- (dimethylaminomethyl) -12 hydroxy-9,10-dihydro-9,10-ethano-anthracene.



   Example 2
The following compounds can be obtained by oxidation of the corresponding 12-hydroxyl compounds: a) 9 - (γ-methylaminopropyl) -12-oxo-9,10-dihydro-
9,10-ethano-anthracene-methanesulphonate, b) 9- (ethylaminomethyl) -12-oxo-9,10-dihydro 91 0-ethano-anthracene, viscous oil, c) 9- (benzylaminomethyl) -12-oxo-9 , 10-dihydro
9,10-ethano-anthracene hydrochloride, d) 9 - (?

  ; -Dimethylaminopropyl) -12-oxo-9,10- dihydro-9,10-ethano-anthracene hydrochloride, e) 2,6-dichlol 9- (dimethyiaminomethyl) -1 2-oxo-
9,10-dihydro-9,10-ethano-anthracene methanesulfonate, f) 9- (diethylaminomethyl) -12-oxo-9,10-dihydro
9,10-ethano-anthracene and g) 9- (dimethylaminomethyl) -12-oxo-9,10-dihydro
9,10-ethano-anthracene, F. 149-153, F. des
Hydrochloride 149-1539.



   PATENT CLAIM 1
Process for the preparation of N-substituted
9- (Aminoalkyl) -9,10-dihydro-9,10-ethano anthracenes which have a hydroxyl group in the 12-position, and their salts. characterized in that in a 9,10-dihydro-9,10-ethano-anthracene which has an acyloxy group in 12-Steiiung and an N-substituted Aiminoalkylrest in 9-position, or in a salt thereof, the acyloxy group for Hydroxyl group reduced.



   SUBCLAIMS
1. The method according to claim I, characterized in that one starts from compounds in which the 12-acyloxy group is a lower alkanoyloxy group.



   2. The method according to claim I, characterized in that one reduces with lithium aluminum hydride.



   3. The method according to claim I, characterized in that in compounds obtained in which the amino group of the aminoalkyl group is a secondary amino group or an N'-unsubstituted piperazino group, aliphatic radicals are formed in these by reaction with a reactive ester of a corresponding alcohol or an epoxide Introduces character.



   4. The method according to claim I or one of the dependent claims 1 to 3, characterized in that compounds of the formula
EMI4.1
 wherein alk denotes a lower alkylene radical with 1 to 3 carbon atoms, R "denotes a mono- or di-lower alkylamino group, a benzylamino group,

   an optionally in the ring / S-monounsaturated and / or C-lower alkylated piperidino or pyrrolidino group or an optionally C-lower alkylated morpholino, thiomorphol, amino, piperazino, N'-lower alkyl, piperazino or N '- (hydroxy lower alkyl) - piperazino group and R1 and R2 are lower alkyl groups, lower alkoxy groups, halogen atoms, nitro groups or hydrogen atoms, or they are salts.



   5. The method according to dependent claim 4, characterized in that compounds of the formula shown in dependent claim 4 are prepared in which R @ is a mono- or dimethylamino group and R1 and R. are hydrogen.

 

   6. The method according to claim I or one of the dependent claims 1 to 3, characterized in that any isomer mixtures obtained are separated into the isomers.



   7. The method according to claim I or one of the dependent claims 1 to 3, characterized in that any racemates obtained are cleaved into the optical antipodes.



   8. The method according to claim I or one of the dependent claims 1 to 3, characterized in that the salts obtained are converted into the free bases.

** WARNING ** End of DESC field could overlap beginning of CLMS **.



   

 

Claims (1)

** WARNING ** Beginning of CLMS field could overlap end of DESC **. a) 9- (ethylaminomethyl) -12-hydroxy-9,10-dihydro 9,10-ethano-anthracene, F. 142, F. des Hydrochlorids 246, b) 9- (diethylaminomethyl) -12-hydroxy-9,10-dihydro-9,10-ethano-anthracene, F. 114-116, F. des hydrochloride 239-240 ^, c) 9- (benzylaminomethyl) -12-hydroxy-9,10 dihydro-9,10-ethano-anthracene, F. 120-121, F. des hydrochloride 278-279, d) 9 - (γ-methylaminopropyl) -12-hydroxy-9,10-dihydro-9,10-ethano-anthracene, F. 132-135, F. des methanesulfonate 168-170, e) 9 - (γ-dimethylaminopropyl) -12-hydroxy-9,10-dihydro-9,10-ethano-anthracene hydrochloride, f) 9 - [γ; ;-( N '- [ss-hydroxyethyl] piperazino) - propyl] - 2-hydroxy-9, 1 0-dihydro- 9,10-ethano-anthracene dihydrochloride, g) 9- (γ-morpholinopropyl) -12-hydroxy-9,10-dihydro-9,10-ethano-anthracene-methanesulfonate, h) 9- (γ-pyrrolidinopropyl ) - 1 2-hydroxy-9, 10-dihydro-9, 10-ethano-anthracene, i) 9 - (γ-piperidinopropyl) -12-hydroxy-9,10-dihydro-9,10-ethano-anthracene methanesulfonate, k) 9- (cyclopropylaminomethyl) -12-hydroxy 9,10-dihydro-9,10-ethano-anthracene, l) 9-dimethylaminomethyl) -12-methyl-12-hydroxy 9,10-dihydro-9,10-ethano-anthracene and m) 2,6-dichloro-9- (dimethylaminomethyl) -12 hydroxy-9,10-dihydro-9,10-ethano-anthracene. Example 2 The following compounds can be obtained by oxidation of the corresponding 12-hydroxyl compounds: a) 9 - (γ-methylaminopropyl) -12-oxo-9,10-dihydro- 9,10-ethano-anthracene-methanesulphonate, b) 9- (ethylaminomethyl) -12-oxo-9,10-dihydro 91 0-ethano-anthracene, viscous oil, c) 9- (benzylaminomethyl) -12-oxo-9 , 10-dihydro 9,10-ethano-anthracene hydrochloride, d) 9 - (? ; -Dimethylaminopropyl) -12-oxo-9,10- dihydro-9,10-ethano-anthracene hydrochloride, e) 2,6-dichlol 9- (dimethyiaminomethyl) -1 2-oxo- 9,10-dihydro-9,10-ethano-anthracene methanesulfonate, f) 9- (diethylaminomethyl) -12-oxo-9,10-dihydro 9,10-ethano-anthracene and g) 9- (dimethylaminomethyl) -12-oxo-9,10-dihydro 9,10-ethano-anthracene, F. 149-153, F. des Hydrochloride 149-1539. PATENT CLAIM 1 Process for the preparation of N-substituted 9- (Aminoalkyl) -9,10-dihydro-9,10-ethano anthracenes which have a hydroxyl group in the 12-position, and their salts. characterized in that in a 9,10-dihydro-9,10-ethano-anthracene which has an acyloxy group in 12-Steiiung and an N-substituted Aiminoalkylrest in 9-position, or in a salt thereof, the acyloxy group for Hydroxyl group reduced. SUBCLAIMS 1. The method according to claim I, characterized in that one starts from compounds in which the 12-acyloxy group is a lower alkanoyloxy group. 2. The method according to claim I, characterized in that one reduces with lithium aluminum hydride. 3. The method according to claim I, characterized in that in compounds obtained in which the amino group of the aminoalkyl group is a secondary amino group or an N'-unsubstituted piperazino group, aliphatic radicals are formed in these by reaction with a reactive ester of a corresponding alcohol or an epoxide Introduces character. 4. The method according to claim I or one of the dependent claims 1 to 3, characterized in that compounds of the formula EMI4.1 wherein alk denotes a lower alkylene radical with 1 to 3 carbon atoms, R "denotes a mono- or di-lower alkylamino group, a benzylamino group, an optionally in the ring / S-monounsaturated and / or C-lower alkylated piperidino or pyrrolidino group or an optionally C-lower alkylated morpho lino, thiomorphol-amino, piperazino, N'-lower alkyl, piperazino or N '- (hydroxy lower alkyl) - piperazino group and R1 and R2 are lower alkyl groups, lower alkoxy groups, halogen atoms, nitro groups or hydrogen atoms, or they are salts. 5. The method according to dependent claim 4, characterized in that compounds of the formula shown in dependent claim 4 are prepared in which R @ is a mono- or dimethylamino group and R1 and R. are hydrogen. 6. The method according to claim I or one of the dependent claims 1 to 3, characterized in that any isomer mixtures obtained are separated into the isomers. 7. The method according to claim I or one of the dependent claims 1 to 3, characterized in that any racemates obtained are cleaved into the optical antipodes. 8. The method according to claim I or one of the dependent claims 1 to 3, characterized in that the salts obtained are converted into the free bases. 9. The method according to claim I or one of the Subclaims 1 to 3, characterized in that the free bases obtained are converted into the salts. PATENT CLAIM II Use of the 12-hydroxy compounds obtained according to patent claim I for the preparation of the corresponding 12-oxo compound, characterized in that the hydroxy group in the 12-hydroxy compounds obtained is oxidized to the oxo group.