PRODUCTION OF GLYCOSIDES, ESPECIALLY OF STEROIDAL GLYCOSIDES

Abstract: For a production of glycosides, especially of steroidal glycosides, molecular iodine is used as a reaction catalyst, wherein an alcohol and/or phenol, especially a hydroxy-steroid, is glycosylated, such that the glycosylation is performed in one single step and without extensive laboratory measures, such as nitrogen gassing and/or extremely high temperatures, and the avoidance of halogenated glycosides and toxic reaction catalysts, such as for example Ag2O, Ag2CO3, PbCO3, Hg(CN)2, etc. and the avoidance of the formation of ortho esters. The steroidal glycoside obtained in this way possesses valuable pharmacological properties, in particular it exhibits a cell-destruction activity free of side effects on malignant cells and a drive-enhancing activity as well.

Description: Production of glycosides, especially of steroidal glycosides Field of the invention This invention relates to at method for the production of a glycoside by glycosylation of an alcohol and/or a phenol, preferably a hydroxy-steroid, as well as a steroidal glycoside and a medicament containing;, the same. An object of the invention is a method for the production of a glycoside and the steroidal glycoside according to the invention as well as the provision thereof as a therapeutically-active substance, medicaments based on this steroidal glycoside for control dδ: prevention of diseases, especially for treatment of cancer-diseases, geriatric diseases, states of hyperactivity and/or states of diminished activity, or for the manufacture of a medicament for the treatment of cancer disease's, geriatric diseases, states of hyperactivity and/or states of diminished activity. Background of the invention The glycosylation of alcohols and/or phenols and particularly that of hydroxy-εteroids is known per se; however, often there arise undesired oistho esters as e.g. described in Chemical Abstracts, Vol. 105, 1986, 172882s. A method which allows the content of this undesired ortho ster to be decreased is disclosed in Chemical Abstracts, Vol. 104, 1986, 22511g (Liebigs Ann. Chem. 1986, 717-7300 / however, this method does not allow the complete avoidance of the formation of ortho esters, and, further, a plvalOylglucopyranosylbromide must be used, wherein the pivaloyl proups function as protecting groups to suppress the form tion <3£ ortho esters. The reaction of the glycoside with the steroid proceeds by means of silver oxide or silver carbonate catalysts. The use of α.-haiogen-tetraaceti'lglucose which is commonly used for the glycosylation of steroids, especially that of cholesterol, necessitates the use of expensive and/or toxic reaction catalysts, such as Ag 2 0, Ag 2 C0 3 , PbC0 3 , Hg(CN) 2 etc., which frequently prohibits its technical application on a larger scale. Furthermore, these glycosylation procedures generally constitute multistage processes which also lead to the production of - as well a.i to β-glycosylation. This invention solves the problem of providing a novel glycoside, especially a steroidal glycoside, for pharmacological application. The glycosylation for the production thereof proceeds in one step and without extensive laboratory measures, such as nitrogen gassing and/or low temperatures, and avoids halogenated glycosides and the utilization of toxic reaction catalysts, such as for example Ag 2 0, Ag 2 C0 3 , PbC0 3 , Hg(CN) 2 etc. and avoids the formation of ortho esters. Summary of the invention It has been surprisingly found that members selected from the group consisting of alcohols and phenols and preferably hydroxy-steroids, wherein hydroxy-steroids are to be understood as members selected from the group consisting of steroidal alcohols and steroidal phenols, can be reacted with a glycosidic vinyl ether in the presence of molecular iodine as a catalyst in one step to yield a glycoside in high yield. Thus there is no need for expensive and toxic reagents in this reaction step. Furthermore, a steroidal glycoside has been found which is obtainable by this method and which can be employed as a highly efficient medicament, especially as an anti-cancer agent, in geriatric: medicine, as a sedative and/or activity-enhancing agent. Method of treating symptoms of at least one member selected from the group consisting of cancer disease- geriatric disease, states of restlessness and states of weakness, comprising administering to a patient suffering from cancer disease, geriatric disease, states of restlessness as states of weakness a pharmaceutical effective amount of a compound of the formula: In the accompanying drawings with reference to preferred examples of the invention: Diagram 1 is an infrared spectrum of the glucal used in the reaction of Example 1; Diagram 2 is an infrared spectrum of the glycosylation product of Example 1; Diagram 3 is an NMR-sectrum of the same glycosylation product of example 1; Diagram 4 and 5 are the IR-spectrum and the NMR-spectrum, respectively of the ketone product of example 2; X Diagrams 6 and 7 are the IR-speetrum and the NMR-spectrum, respectively, of the 7.3-OH Cholesterol" roduct of example 3; and Diagram 8 is a plot showing the tumor cell groth inhibit; on by selected concentrations of 7J3-OH cholesterol in cell culture field. Detailed description of the invention According to one preferred embodiment of the method of the invention r an oxysteryl compound, preferably a 3β-ol sterol compound, more preferably a k delta 5 -3β-ol steroid compound such as a cholesterol, (e.g., delta 5 -cholesten-3B-ol) is glycosylated by reaction with: 3,4,6-tri-O-acetyl-D-glucal in an inert solvent in the presence' of molecular iodine as a catalyst. The reaction is achieved in one single step and in high yield. Thus a double bond which is strongly hindered by the C 4 , C 6 -acetyl groups and thus being inert, is introduced between C 2 =C 3 of the glycosidic part of the molecule, whereby the delta 5 double bond of the perhydro-cyclopentano- phenanthrene skeleton remains unchanged. Furthermore, the reaction of the unsaturated glycoside which is obtained as an intermediate to functional cholesterol derivatives is performed according to the method of this invention. Functional groups can be introduced into the perhydro-cyclopentano-phenanthrene skeleton of said unsaturated acetoglycoside, wherein the α-bond of the acetoglycoside at the same time functions as a protecting group for the original OH-group at C 3 of the phenanthrene skeleton. In contrast to the analytical procedure for the iodometric assay of vinyl ethers by ionized iodine in alcohol with formation of the corresponding iodoacetals according to S. Siggia and R. L. Edsberg, Ind. Eng. Chem. Anal. .20., 762 (1948), thereby using ionized iodine in the reaction, the method according to this invention makes use of iodine being molecularly dissolved in inert solvents such as for example CH 2 C1 2 dichloromethane, CHC1 3 chloroform, CC1« carbon tetrachloride, C 6 I CH 3 ) 2 xylene, C 6 H 3 (CH 3 ) 3 mesitylene, C 6 H 5 CH(CH 3 ) Z cymene, C 6 H 12 cyclohexane and methyl derivatives thereof, as well as ligroin, petroleum ether and saturated hydrocarbons, such as for example n-pentane or n-heptane, preferably C 6 H 6 benzene or C 6 H S CH 3 toluene. The method according to the invention is applicable to the glycosylation of hydroxy compounds in general and broadly, e.g. all compounds with free alkoholic HO-groups as for example prim., sec, or tert. alcoholic groups, aliphatic, aliphatic- aromatic or aromatic. Preferred hydroxy compounds for glycosylation comprise cholesterols, bile salts, steroid hormones, and vitamin D compounds and precursors as described in Stryer's Biochemistry, 3rd Ed. pp. 559-570, Freeman and Company, New York, 1988, incorporated herewith by reference. Specifically stero-fed se^iyati e such as: Cholic acid and derivatives, 25 ^ hydroχy-choiesterol, 25-hydroxy-calciferol, Pregnenolone, 17α-hydroxy*pregnenόlohe, 17α-hydroxy- progesterone, ll-desoxy-cόrticosteron, 11-desoxy-cortisol, corticosterone, cortisol, cortison , androsterone, testosterone, estrone, 17β-estradiol, estratriol-3, 16α, 17β, 3α, 5β-tetrahydro-corticosterone, -C-Cortisol and allocortolon preferably cyclopentano-perhydrophenanthrene compounds having the delta 5 -3β-OH steryl moity. 1, to the steroidal glycoside according to this invention, to the 3B-0-(4,6-dihydroxy-2,3-dideoxy-D-erythro-α-2-hexyl)- delta 5 -cholesten-7β-ol of formula 530,75* This compound posesses valuable pharmacological properties, in particular it exhibits a cell-destructive activity - free of side effects - on malignant cells and a drive-enhancing activity as well as a tranquilizing activity. The steroidal component, the delta 5 -cholesten-3β,7β-diol, constitutes an own steroid of the thymus gland being a native signal substance of the cellulary immune response which previously has been successfully employed in the treatment (free of side effects) of cancer diseases of all phenotypes. Whereas the delta 5 -cholesten-3β,7α-diol is formed in the liver as the first degradation product of cholesterol and posesses no physiological activity; the delta 3 -cholesten-3β,7β-diol is formed in the thymus gland of all mammals as a universal signal substance of their own immune defence. It owes its activity, which is solely directed to malignant cell surfaces, to the fact that it is bound unspecifically by LDL (low density lipoproteins), which are responsible for the essential transport of cholesterol into the interior of the cell and for the construction of the cell membranes, and that it is transferred by the latter ones, presumably via the NK-cells (natural killer cells) onto the cell membranes of deviated tissue, particularly onto cancerous tissue. As, in contrast to normal soma cells, the receptors of LDL on the surface of cancer cells are degeneratively modified, having undergone a modification of their spatial structure, the 7β-hydroxy- cholesterol effects a blocking of the receptors modified in this way-. This is comparable to the plug of a bottle, wherein the cancer cell is cut off from the supply of the vital cholesterol. Hence it follows that an osmotic excess pressure builds up in the interior of the cancer cell, finally leading to the colloid-osmotic indu'ced rupture of the cancer cell. The cytoplasma of the cancer cej.1 is then forced out. Thus the cancer cell ceases to exist (Diagram 8). This method, lasting only f«or about 8 to 10 minutes, has been investigated microscopically and recorded by Alex Matter (Microcinematographic and electron microscopic analysis of target cell lysis induced by cytotoxic T lymphocytes, Immunology 36, 179 - 190 (1979)). No statement concerning the chemical nature of the body's own active substance is made. 7β-Hydroxy-cholesterol was detected, together with progesterone, lLβ-hydroxy-progesterone, cortexone and 7-keto- cholesterol, in thymus extracts for thre first time in 1976 by Klemke (unpublished resuJ ^ ts , using t|ire antimony trichloride reaction for stenols, Iξ-spectxoscopy and NMR-spectroscopy. Lateron Reisch and El Shakary, Scientia Pharmaceutica 50, 75-78 (1982) confirmed these findings after the group of J. P. Beck in Strasbourg, J. Chem-. Res. (S) 1977, 217 - 219, had previously found that 7β-h iroxy-cholesterol constitutes the antiproliferatory active substance of a very ancient Chinese Further details have been fjablished--in Vol. 32/ TUMOSTERON "Schriftenreihe Krebsgeschehen" of the Verlag fur Medizin, Heidelberg 1986. The delta 5 -*cholesfcem-3β,7β-diol was recognized as a biochemical signal compound of the body's own immune defence system. In contraststo the conventional cytotoxic treatment of cancer diseases this turns out to be completely non-toxic and to be capable^ o eliminating cancer cells of any phenotype and not affecting-healthy cells. - It is true that a glycosylated cholesterol is known from Chemical Abstracts Vol. 97, 1982 6t7~ ' 3'4s, which possibly might constitute a neoplastic inhibitor; " however this molecule has in its glycosidic moiety at -f'S. bulky 2-bhloroethyl-amino- carboxamido group and at C "'djf the cholestero the 7β-hydroxy group is lacking. This latter group, however, is important for the activity of the steroidal glycoside according to the invention, as this steric array is also important for the respective cellular receptor. In the treatment method of the invention the compound according to the invention can be used as a medicament in the form of pharmaceutical preparations comprising this compound in admixture with a pharmaceutically acceptable carrier. One skilled in the art of preparing formulations can readily select the proper form and method of administration depending upon the particular characteristics of the compound selected, the disease state to be treated, the stage of disease, and other relevant circumstances. These preparations can be administrated orally, e.g. in the form of tablets, dragees, gelatin capsules, soft capsules, solutions, emulsions or suspensions or parenterally, e.g. in the form of injectable solutions or topically, e.g. in the form of cream. The compound can be administered alone or in the form of a pharmaceutical composition in combination with pharmaceutically acceptabel carriers, preservatives, solubilizers, stabilizers, humectants, emulsifiers, sweetening agents, dyes, scents, salts to modify the osmotic pressure, buffers, coating agents, antioxidants such as for example tocoquinones (tocopheroles), glutathione, cystein, ascorbic acid sodium salt etc. The carriers mentioned above may constitute pharmaceutically inert anorganic or organic materials. Examples of carriers for tablets, capsules and hard gelatine capsules include lactose, maize-starch or derivatives thereof, talcum, stearic acid or salts thereof. Examples of carriers for soft gelatine capsules are vegetable oils, waxes, fats, semi-solid and liquid polyols. Examples of carriers for the manufacture of solutions or syrups include water, polyols, saccharose, inverted sugar and glucose. Examples of carriers for injectable solutions include water, alcohols, polyols, glycerol and vegetable oils. The pharmaceutical preparations may also comprise conventional pharmaceutical adjuvants such as preservatives, solubilizers. stabilizers, humectants, emulsifiers, sweetening agents, dyes or scents, salts to modify the osmotic pressure, buffers, coating agents or antioxidants. They may also include other therapeutically valuable ingredients. 5 The pharmaceutical preparations may be manufactured by admixing the compound according to this invention, if desired in combination with other therapeutically valuable substances, with an acceptable pharmaceutical carrier and, if desired, with 10 a pharmaceutical adjuvant, and, transforming the admixture into the desired form for administration. Dosages: 15 In the treatment of cancer a dosage of at most 80 mg per day, preferably 10 mg to 30 mg per day, more preferable 10 mg to 20 mg. For the purpose of parenteral therapeutic administration, the 20 compound of the present invention may be incorporated into a solution or suspension. These preparations should contain at least 0.1 % of a compound of the invention, but may varied to be between 0.1 % and about 50 % of the weight thereof. The amount of this inventive compound presents in such compositions 25 is such that suitable dosage will be obtained. Preferred compositions and preparations according to the present invention are prepared so that a parenteral dosage unit contains between 5 mg to 80 mg, more preferred 5 to 40 mg, most preferred 10 to 40 mg. 30 A therapeutically effective dose can be readily determined by the attending diagnosticians, as one skilled in the art, by the use of conventional techniques and by observing results obtained .under analoguous circumstances. In determing the 35. therapeutically effective dose, a number of factors are considered by the attending,diagnostician, including, but not limited to: the species of mammals, the size, age and general response of the individual patient; the particular compound administered; the mode of administration; the biovailability characteristics of the preparation administered; the dose regimen selected; the use of concomitant medication; and other relevant circumstances. A therapeutically effective amount of a compound according to the invention is expected to vary from about 0.07 mg per 1 kg of body weight per day ( g/kg/day) tύ about 1.25 mg/kg/day. Preferred amounts are expected to vary from about 0.15 mg/kg/day to about 0.3 mg/kg/day. The reaction steps described subsequently are disposed as follows: 11 Example 1 Preparation of 3B-0- , 4 , 6-0-acetyl-2 , 3-did&oxV"D-eιrythro-α-hexyl . -delta 5 - cholestene 5.0 g (= 0.02 mole) olecular iodine were dissolved with Stirling in 300 ml benzene in et 2-litre three-necked flask fitted with stirrer, reflux condenser and thermometer. To the wine-red solution thus obtained was added the solution of 27.2 g and 38 « 6 9 (= 0.10 benzene. In the course of 2 hours"-the mixture was heated to 70-75 °C. The reaction was monitored by fR-spec roscOpy; it was terminated only when the peak of the g ucal at 1650 cm "1 (Diagram 1) has disappeared. The red colour of the reaction solution is not significant. After removal of the flask heater the reaction solution is rapidly cooled ish a waters-bath to about 20-30 °C. After transfer into a 2-litre separatory funnel the cooled wine-red reaction solutioϊVVas extracted until complete discoloration with 500 ml + "lO of 0.1 N = 12.5 g + 10 % = 13.8 g aqueous solution of Na 2 SO*, washed twice with water, treated with activated carbon, dried over anhydrous Na 2 S0 4 - and -the solvent is distilled off, finally in vacuo. *^ Crude yield: 58.3 g (= 97. % ^ th.). The raw product is recrysta ized from 2 litres of CH 3 OH. Yield: 56.95 g \ -~ 95 1% th.) 1 Mp: 118-120 °C " IR-spectrum: Diagram 2 NMR-spectrum: Diagram 3 ~ -$ Example 2 Preparation of 3β-0-.4,6-0-ace1.yl-2,3-dideoxy-D-ervthro-α-2- hexyl .-delta 5 -cholesten-7-one In a 250 ml three-necked flask fitted with reflux condensor, dropping funnel, thermometer and magnetic stirrer 6.00 g (= 0.01 mole) of the unsaturated glycoside from Example 1 of mp 118-120 C 'C were dissolved in 45 ml of CC1 A and heated to boiling (80 °C). In the coujrse of 30 minutes the mixture of 10 mi Ac 2 0 (acetic anhydride) and 40 ml t-butyl chromate, prepared according to the Annex, was slowly added dropwise to the boiling solution and stirred for another 10 hours at the boiling point. After cooling, a solution of 6.0 g oxalic acid in 60 ml water was added dropwise in the course of 45 minutes at 5 °C to 10 °C in an ice-bath followed, by 4.2 g solid oxalic acid. Stirring was then continued for another 2 hours. Thereafter separation took place in the separating funnel, the upper dark aqueous phase being extracted twice with CCl ή , the combined CCl_,-solutions extracted with water, saturated solution of NaHC0 3 and then with water again, in this order, and dried over Na 2 SO«. ■Finally the solution was discolored with activated carbon. After concentration in vacuo the straw-yellow residue was dissolved in 25 ml of a mixture consisting of cyclohexane 40 : ethyl acetate 10 : chloroform 1 and chromatographed on a silica gel column (diameter 2.5 cm; height 25 cm), charged with 60 g of silica gel 40 (Merck Article 10180) and the same solvent mixture. " Yield: Fraction 1: 1.8 g (= 30.1 % of theory) unchanged starting material * Fraction 2: 4.2 g (= 68.5% of theory) 7-keto-compound Mp: 113-115 °C IR-spectrum: Diagram 4 NMR-spectrum: Diagram 5 Anne : Preparation of t-butyl chromate In a 500 ml beaker, 187.2 g (= 2.5 mole) t-butanol of mp 24.5 °C were warmed to 28 °C and melted. To this melt, 74 g (= 0.74 mole) of Cr0 3 were added by using a thermometer as-a stirring bar. In order to keep the reaction temperature below 30 °C, occasional cooling with ice-water was necessary. The liquid reaction product was- diluted in a separating funnel with 520 ml of CC1 < and left to stand overnight. This standing is important to allow clarification of the solution. The following morning, the upper dark layer was separated. The clear CCl 4 -solution was dried with 50 g of anhydrous Na 2 S0 4 , filtered and the Na 2 S0 4 washed with 320 ml of CC1 4 . Thereafter, the combined CCl 4 -solutions were concentrated to 400 ml in vacuo in a water-bath at a temperature of 40 °C to 45 °C, wherein excess t-butanol and CC1 4 were both distilled azeotropically. The solution thus obtained may be kept unchanged in the refrigerator at -1 °C for at least one month. Example 3 Preparation of 3β-0- (4,6-Hvdroxy-2,3-dideoxy-D-ervthro-o_-2- hex l .-delta 5 -cholesten-7β-ol 6.13 g (= 0.01 mole) of pure compound from Example 2 with mp 113-115 °C were dissolved by heating in 100 ml peroxide-free ether which has been dried with metallic sodium and cooled to room temperature. A solution of 0.8-1.0 g (= 0.021 mole) LiAlH A in 100 ml absolute ether was added to a 500 ml three-necked flask with magnetic stirrer, reflux condensor and thermometer. The ethereal solution of the unsaturated aceto-7-keto-glucoside was then added dropwise with sufficient stirring such that the reaction temperature did not substantially exceed 20 °C, if possible. After addition had been terminated, which may take up to two hours, stirring was continued for another 2 hours. Afterwards, the reaction mixture was cooled in ice-water and treated drop by drop with H 2 0 until all H 2 (conducted to the outlet of the hood by means of a tube) had evolved. H 2 0-consumption was about 5.0 ml. On a larger scale, the use of CH 3 COOC 2 H 5 is recommended. In order to dissolve the LiA10 2 formed, the solution was stirred with 16 ml of 10% H 2 S0 4 and, after transfer to a 500 ml separating funnel, diluted with 100 ml of ether and shaken thoroughly. Thereby, the reaction product, which has separated as crystals, goes completely into solution. The acidic aqueous solution was extracted once with ether and the combined ethereal solutions washed with 100 ml of a saturated NaCl-solution in two portions of 50 ml each. After drying over anhydrous Na 2 S0«, the filtrate was kept in the refrigerator at -1 °C for 9 hours. The crystals thus obtained are collected by suction over a G4-suction filter and weighed. Crude yield: 5.10 g (= 96.23% of theory) mp: 165 -167 °C This compound was dissolved in-25 ml of dioxane by heating and chromatographed on a column of. silica gel (diameter 5.0 cm; height 70 cm) charged with 300 g of silica gel 40 (Merck Article 10180) using a solvent • mixture consisting of dichloromethane 1 : acetone 1. Yield: Fraction 1: 0.35 g (= 6.8%) 7o_--OH-compound, mp: 161-195 °C. Fraction 2: 4.60 g (= 90.2%) 7β-OH-compound, mp: 181-183 °C. IR-spectrum: Diagram 6 NMR-spectrum: Diagram 7

Claims: Claims 1. Method for the production of a glycoside, comprising glycosylating at least one member selected from the group consisting of an alcohol and a phenol by reaction with a glycosidic vinyl ether in the presence of a catalytic amount of molecular iodine. 2. Method according to Claim 1, wherein said at least one member selected from the group consisting of an alcohol and a phenol is a hydroxy-steroid. 3. Method according to claim 2, wherein the hydroxy-steroid is delta 5 -cholesten-3β-ol and the glycosidic vinyl ether is 3,4,6-tri-O-acetyl-D-glucal. 4. Method according to claim 3, wherein the product formed by the glycosylation is 3β-0-(4,6-0-diacetyl-2,3-dideoxy-D-erythro- -2-hexyl)-delta 5 - cholestene. 5. Method according to claim 4, further comprising oxidizing the 3β-0-(4,6-0-diacetyl-2,3-dideoxy-D-erythro- -2-hexyl)-delta 5 - cholestene with an oxidizing agent to form a first product and then reducing said first product with a metal hydride reducing agent to form a second product. 6. Method according to claim 5, wherein said first product is 3β-0-(4,6-0-diacetyl-2,3-dideoxy-D-erythro-α-2-hexyl)-delta 5 - cholesten-7-one. 7. Method according to claim 5, wherein said second product is 3β-0-(4,6~-dihydroxy-2,3-dideoxy-D-erythro- -2-hexyl)-delta 5 - cholesten-7β-ol in admixture with 3β-0-(4,6-dihydroxy- 2,3-dideoxy-D-erythro-α-2-hexyl)-delta 5 -cholesten-7α-ol. 8. Method according to claim 5, wherein said oxidizing agent is t-butyl-chromate, pyridine-chromium trioxide or pyridine chlorochromate. 9. Method according to claim 5, wherein said reducing agent is LiAlH 4 LiBH A , NaBH 4 or BH 4 . 10. Method according to claim 7, further comprising separating the 3β-0-(4,6-dihydroxy-2,3-dideoxy-D-erythro- -2-hexyl)- delta 5 -cholesten-7β-ol from the 3β-0-(4,6-dihydroxy- 2,3-dideoxy-D-erythro- -2-hexyl)-delta 5 -cholesten-7 -ol. 11. Method according to claim 10, wherein said separated 3β-0-(4,6-dihydroxy-2,3-dideoxy-D-erythro-α-2-hexyl)-delta 5 - cholesten-7β-ol is processed with a pharmaceutically acceptable carrier to form a pharmaceutical composition. 12. Compound..of formula 530, 1SS 13. Medicament which comprises a pharmaceutically effective amount of 3β-0-(4,6-dihydroxy-2,3-dideoxy-D-erythro- α-2-hexyl)-delta 5 -cholesten-7β-ol together with another pharmaceutically acceptable ingredient. 14. Method according to Claim 13, wherein said another ingredient is selected from the group consisting of carriers, " preservatives, solubilizers, stabilizers, humectants, emulsifiers, sweetening agents, dyes, scents, salts to modify the osmotic pressure, buffers, coating agents, antioxidants. 15. Medicament according to claim 13, wherein said amount is effective to treat symptoms of at least one member selected from the group consisting of cancer " disease, geriatric disease, states of restlessness and states of weakness. 16. Method of treating symptoms! of at least " one member selected from the group consisting of cancer disease, geriatric disease, states of restlessness"and states of weakness, comprising administering to a patient suffering from cancer disease, geriatric disease, states of restlessness as states of weakness a pharmaceutically effective amount of a compound of the formula: 17. Method according to claim 16, wherein said compound is administered to said patient in admixture with another pharmaceutically acceptable ingredient. 18. Method according to clfaim 17, wherein said another ingredient is selected froϊή the group "consisting of carriers, preservatives, solubilizers 1 , stabilizers, humectants, emulsifiers, sweetening " agents, dyes, scents, salts to modify the osmotic pressure, buffers, coating agents, antioxidants. 19. Method according to clefim 16, wherein said compound is administered in a form selected from the group consisting of tablets, -dragees, pills, gelatin capsule's, soft capsules, suppositories, solutions, emulsions, suspensions, injectable . solutions, troches, liniments, salves, ointments, creams. 20. A glycoside formed by the process comprising glycosylating delta 5 -cholesten-3β-ol by reaction with 3,4,6-tri-O-acetyl-D- glucal in the presence of a catalytic amount of molecular iodine to form a first product. 21. A glycoside according to claim 20, wherein said process further comprises oxidizing said first product with t-butyl- chromate to form a second product, reducing said second product with LiAlH 4 to form a mixture of glycosides, and isolating from said mixture of glycosides a glycoside which includes a 7β-ol moiety. 22. A glycosidic vinyl ether of an hydroxy compound selected from the group containing cholesterols, bile salts, steroid hormones, and vitamin D compounds. 23. A glycosidic vinyl ether according to claim 22 wherein the hydroxy compound is selected from the group containing cholic acid and derivatives, 25-hydroxy-cholesterol, 25-hydroxy- calciferol, Pregnenolone, 17 -hydroxy-pregnenolone, 17 - hydroxy-progesterone , 11-desoxy-corticosteron, 11-desoxy- cortisol, corticosterone, cortisol, cortisone, androsterone, testosterone, estrone, 17β-estradiol, estratriol-3, 16α, 17β, 3α, 5β-tetrahydro-corticosterone, urocortisol and allocortolone. 24. A method according to claim 1, wherein said member is an hydroxy-steroid and wherein said hydroxy-steroid is selected from the group containing cholic acid and derivatives, 25- hydroxy-cholesterol, 25-hydroxy-calciferol, Pregnenolone, 17o_- hydroxy-pregnenolone, 17 -hydroxy-progesterone, 11-desoxy- corticosteron, 11-desoxy-cortisol, corticosterone, cortisol, cortisone, androsterone, testosterone, estrone, 17β-estradiol, estratriol-3, 16α, 17β, 3α, 5β-tetrahydro-corticosterone, urocortisol and allocortolone.

Inventors: KLEMKE RUDOLF ERICH DIPL CHEM, KLEMKE, RUDOLF, ERICH
Applicants: HARRIER GMBH, "HARRIER" GMBH GESELLSCHAFT FUER DEN VERTRIEB MEDIZ
Application year: 1991
Main classification: A61K31
IPC codes: A61K9, A61K31, A61P25, A61P35, A61P43, C07J17