PL116228B1 - Process for preparing novel derivatives of 4"-desoxyaminoerythromycin a" - Google Patents

Description

The subject of the invention is a method for preparing new derivatives of 4"-deoxy-4-aminoerythromycin A of the general formula 3a, in which Ri and R2 denote a hydrogen atom or an alkanoyl radical with 2-3 carbon atoms, R3 denotes a hydrogen atom, or R2 and R3 together denote the group -C(O)- when R' is an OH group, R is a bond to the carbon atom to which R' is attached or when R' is =0, R is hydrogen, provided that when R2 is hydrogen , R also represents hydrogen and pharmaceutically acceptable acid addition salts thereof. Erythromycin is an antibiotic produced by culturing a strain of Streptomyces erythreus in a suitable environment, as described in US Pat. No. 2,653,899. Erythromycin is produced in 2 forms A and B with the general formula 5, where the compound of formula 5, in which R is a hydroxyl group, is erythromycin A, and the compound of formula 5, in which R is hydrogen, is erythromycin B. As can be seen of formula 5, this antibiotic consists of three main parts, namely a sugar fragment called cladinose, a second sugar fragment containing a basic amine substituent, called desosamine, and a 14-membered lactan ring called erythronolyte A or B or also macrolide ring. In formula 5, the macrolide ring has positions marked 1-13, desosamine has positions marked 1'-6', and the positions in cladinose are marked 1"-6". In order to obtain erythromycins with different biological and pharmacodynamic properties, a number of erythromycin derivatives have already been produced. From the patent description of St. Zj. Am. No. 3,417,077, the reaction product of erythromycin with ethylene carbonate is known, which is a compound with very high antibacterial activity, and in the St. patent description Zj. Am. No. 3,884,903 discusses the 4"-deoxy-4"-ketoerythromycin A and B derivatives as useful antibiotics. Erythromycylamine, i.e. the 9-amino derivative of erythromycin A, has been the subject of numerous studies [British Patent No. 1,100,504, Tetrahedron Letters , 1645/ /1967 and Croatica Chemica Acta, 39, 273 (1967)], and there is some divergence of views on the structure of this compound [Tetrahedron Letters, 157 (1970) and British patent no. 1,341,022J. According to the patent description St. Zj. Am. No. 3,983,103, sulfonamide derivatives of erythromycylamine are useful as antibacterial agents, and other derivatives are also reported to have antibacterial activity in vivo [Ryden et al., J. Med. Chem., 16, 1059 (1973) and Massey et al., G. Med. Chem, 17, 105 (1974)]. Currently, it has been found that new derivatives of 4/-deoxy-4/-aminoerythromycin A with general formulas 3 and 4, in which Ri is a hydrogen atom or an alkanyl radical with 2 or 3 atoms, have exceptionally beneficial properties as antibacterial agents. carbon, in formula 3 R2 is an alkanoyl radical with 2 or 3 carbon atoms and R3 is a hydrogen atom, or R2 and R3 together are a -C(O)- group, and in formula 4 R4 is a hydrogen atom or an alkanoyl radical with 2 or 3 carbon atoms and R3 is hydrogen, or R3 and R4 together represent the group -C(O)-. Compounds of formula 3 have particularly favorable chemotherapeutic properties, especially those in which R2 and R3 together constitute the C(O)- group. ^l Compounds of formula 4 also have favorable properties, especially those in which R4 is hydrogen and those in which R3 and R4 together represent the -C(O)- group. The pharmacologically acceptable addition salts of the compounds of formulas 3 and 4 also have very good antibacterial properties. The compounds of formulas 3 and 4 can be represented by one general formula 3a, in which the substituents have the meanings given above. Intermediate products in the preparation of compounds of formulas 3 and 4 are compounds of formulas la and 2a, in which Ri has the above-given meaning, in formula la Y stands for the =NOH group or the =N-0-C(0)CH3 group, and in formula 2a R2 stands for an alkanoyl radical with 2 or 3 carbon atoms and R3 represents a hydrogen atom, or R2 and R3 together represent a -C(O)- group. Particularly preferred intermediate products are compounds of formulas Ia and £a, in which Ri represents a hydrogen atom or an acetyl radical. Derivatives of erythromycin B, corresponding to formulas 1 and 2, are also useful as intermediates and are prepared by the same synthesis as derivatives of erythromycin A. Derivatives of erythromycin B are converted by the methods described below into amine derivatives of erythromycin B, corresponding to the compounds of formulas 3 and 4. Preferred intermediate products are: 11,12-carbonate of 6,9-hemiketal 2'- acetyl-4"-deoxy-4"-ketoerythromycin A and 11,12-carbonate of 6,9-hemiketal of 4"-deoxy-4"-ketoerythromycin A. Method according to the invention for preparing new 4''-deoxy derivatives -4''-aminoerythromycin A of the general formula 3a, in which the substituents have the above-mentioned meanings, and their pharmaceutically acceptable acid addition salts, consists in reducing the compound of the general formula Ib, in which R, R', Ri , R2 and R3 have the meanings given above, and Y is the group =N-OH or =N-OCOCH3 or when Y is an oxygen atom, the compound of formula Ib is condensed with an ammonium salt of an alkane-carboxylic acid, then reduced, and then optionally unobtained compounds in which Ri or R2 represent hydrogen atoms are converted into compounds in which Ri or R2 represent alkanoyl groups and/or when Ri or R2 represent alkanoyl groups, they are converted into hydrogen atoms and then the obtained compounds are optionally converted into acid addition salts. The detailed conduct of the process according to the invention is described below. Compounds of formula 3 are prepared from compounds of formula 2a by condensation with an ammonium salt of a lower alkane carboxylic acid and then in situ reduction of the imine produced. The term "lower alkanecarboxylic acid" means tu-acids having 2 to 4 carbon atoms. In practice, a solution of a ketone of formula 2a in a lower alkanol, such as methanol or isopropanol, is treated with an ammonium salt of a lower alkanecarboxylic acid, such as acetic acid, and the cooled mixture the reaction mixture is treated with a reducing agent such as sodium cyanoborohydride. The reaction is carried out at room temperature for several hours, after which the mixture is hydrolyzed and the product is isolated. Although 1 mole of ammonium alkanecarboxylate is required for 1 mole of ketone, the reaction proceeds faster if an excess of ammonium salt is used up to 10: 1. Such an excess of ammonium salt does not adversely affect the quality of the product - The reducing agent, i.e. sodium cyanoborohydride, is preferably used in an amount of about 2 moles per 1 mole. ketone. The duration of the reaction depends on the concentration of the reaction components 5 and their ability to react as well as on the temperature. At room temperature the reaction lasts 2-3 hours. If methanol is used as a solvent, the alkanoyl group in the 2' position is significantly degree of solvolysis and in order to avoid cleavage of this group, isopropanol is preferably used as the solvent. Ammonium acetate is preferably used as ammonium alkanocarboxylate. When isolating the prepared derivatives of 4"-deoxy-4"-aminoerythromycin A, the basic nature is used to separate them from possible non-basic by-products and from the starting product. manufactured products. Namely, the aqueous solution of the product is extracted at a gradually increasing pH value, so that the neutral or non-basic substances are extracted at lower pH values, and 20 the product at a pH value above 5. Ethyl acetate or diethyl ether are used as extraction solvents, the extracts are washed with brine and water, dried over sodium sulfate and the product is isolated by removing the solvent. If necessary, the product is purified by column chromatography on silica gel according to known methods. As mentioned above, the alkanoyl group in the 2r position of the 2'-alkanoyl-4''-deoxy-4'-aminoerythromycin 'A derivative can be removed sblvolysis route, leaving a solution of this compound in methanol for several hours at room temperature. If compounds of formula 2a are subjected to reductive amination, in which R2 and R3 together represent the -C(O)- group and Ri represents a radical alkanoyl b with 2 or 3 carbon atoms or a hydrogen atom, then amines b of both formulas 3 and 4 are obtained, as shown in Scheme 2. The mixture obtained is separated into individual amines by selective crystallization from diethyl ether. Recrystallization of this mixture of acetone with water 40 produces an amine hemiketal of formula 4 and enables the isolation of an amine of formula 3. In a manner analogous to the one described above, by condensation of compounds of formula I with ammonium alkanocarboxylate and then in situ reduction of the produced imine with sodium cyanoborohydride compounds of formula 4 are prepared. Compounds of formula 4, in which Ri, R3 and R4 have the meanings given above, are also prepared by reducing the above-mentioned imine with hydrogen in the presence of a suitable catalyst. A solution of a ketone of formula Ia 50 in a lower alkanol, e.g. methanol or isopropanol, . the ammonium salt of a lower alkanecarboxylic acid, e.g. acetic acid, is treated in the presence of a hydrogenation catalyst and the mixture is shaken in an atmosphere of water until the reaction is completed. Although 1 mole of ammonium salt is required for 1 mole of ketone 55, it is preferable to use even a tenfold excess of salt, because then the imine production reaction proceeds faster. Such an excess of alkali- . ammonium nocarboxylate has no harmful effect on the quality of the product. 60 Various hydrogenation catalysts can be used in this process, but the most preferred ones are Raney nickel or 5-10% palladium on charcoal. Catalysts are used: in different amounts, depending on the desired reaction speed, and preferably the amount of catalyst is 10-200% by weight in relation to the amount of the compound of formula 1. The reaction speed is also influenced by the hydrogen pressure in the vessel. reactionary. Preferably, an initial pressure of 466.5 Pa is used and the reaction is carried out at room temperature. The duration of the reaction depends on a number of factors, including temperature, pressure, concentration of the reaction components and their ability to react. Under the favorable conditions given above, the reaction is completed within 12-24 hours. The product is isolated by filtering off the spent catalyst and evaporating the solvent under reduced pressure. The residue is treated with water and the product is separated from the non-basic by-products by extraction from the aqueous solution at varying pH as described above. As stated above, if methanol is used as the solvent, the alkanoyl radical in the 2' position is largely solvolysed and In order to avoid cleavage of this radical, the reaction is carried out in isopronanol. Compounds of formula 4 can also be prepared by first converting compounds of formula-1 into their oximes or oxime derivatives of formula Ia, in which Y is the =NOH group or the =N group -OC(0)-CH3, and then reducing the obtained oxime or its derivative. Compounds of the formula Ia, in which Y is the group =NOH, *o is the oxime of ketones, are prepared from compounds of the formula 1 by reaction with hydroxylamine hydrochloride and barium carbonate in methanol or isopropanol at room temperature. In practice, it is preferable to use an excess of up to three times hydroxylamine, because then compounds of formula Ia are obtained with good yield. When using excess hydroxylamine and carrying out the reaction at room temperature, the reaction lasts 1-3 hours. Barium carbonate is used in an amount of 2 moles per 1 mole of hydroxylamine hydrochloride. The product is isolated by pouring the reaction mixture into water, making it alkaline to a pH of 9.5 and extracting it with a water-immiscible solvent, such as ethyl acetate. Alternatively, the mixture can be filtered, the filtrate evaporated to dryness and the residue shaken out with an immiscible solvent. with water at a pH value of 9.0-9.5. O-acetyloximes, i.e. compounds of the formula Ia, in which Y is the group =N-OC(0)CH3, are prepared by acetylation of the corresponding oximes. The process can be carried out in such a way that 1 mole of oxime is reacted with 1 mole of acetic anhydride in the presence of 1 mole of pyridine or triethylamine, but preferably an excess of 30-40% of acetic anhydride and pyridine is used. The reaction is preferably carried out in a non-protic atmosphere. solvent, such as benzene or ethyl acetate, at room temperature for several hours. After the reaction, the pH of the mixture is adjusted to 9.0 and the product dissolved in the solvent is separated. Preferred compounds of formula Ia in the preparation of derivatives 4"- deoxy-4"-aminoerythromycin A with antibacterial properties are: 2'-acetyl-4"-deoxy-4"-ketoerythromycin A oxime, 2'-acetyl-4"-deoxy-4"-O-acetyloxime ketoerythromycin A, 4"-deoxy-4"-ketoerythromycin A oxime and 4"-de-xoxy-4"-ketoerythromycin A O-acetylpoxime. Reduction of compounds of formula Ia is carried out by catalytic hydrogenation in solution at a lower an alkanol, such as isoffropanol, by shaking in the presence of Raney nickel in an atmosphere of hydrogen at an initial pressure of 19331 Pa, at room temperature, for several hours. 6 Then the catalyst is filtered off and the solvent is removed, obtaining a compound of formula 4. If methanol is used as a solvent, there is a possibility of cleavage of the alkanoyl radical in the 2' position as a result of solvolysis. In order to avoid this side reaction, it is preferable to use isopropanol. Of the compounds of formulas 3 and 4, both epimers of 11,12-carbonate, 6,9-hemiketal, 4-deoxy-4,,-aminoerythromycin A, have particularly favorable antibacterial properties. 4"-io-deoxy-4"-aniinoerythromycin A and 4"-deoxy-4"-aminoerythromycin A 11,12-carbonate. These compounds of formulas 3 or 4, which form salts, are preferably used pharmacologically in the form of their salts permissible, and salts that are not suitable for use in pharmacology due to their insolubility in water, high toxicity or lack of ability to crystallize can be converted into the corresponding bases or other acid addition salts, suitable for use in medicine. Examples of acids giving anions acceptable in pharmacology are hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, sulfurous acid, phosphoric acid, acetic acid, lactic acid, citric acid, succinic acid, maleic acid, glyconic acid and aspartic acid. As mentioned above, the stereochemical structure of pro - The 25 starting products from which compounds with antibacterial properties are prepared according to the invention are the same as the corresponding compounds of natural origin. Oxidation of the hydroxyl group in the 4" position to a ketone group and then transformation of this group into an amino group in the 4-position provides one possibility of stereochemically changing the substituent in the 4" position and producing products with a structure different from the structure of products of natural origin. Namely, by processing the compounds of formulas 1, 2, la or 2a in the manner described above into their corresponding amine derivatives, it is sometimes possible to prepare mixtures of both amine epimers of formulas 3 and 4, and it was found that the content of these epimers in the mixture depends on method of conducting the process. If the isolated product contains mainly one epimer, this epimer can be purified by repeated recrystallization from a suitable solvent until a product with a constant melting point is obtained. The second epimer, present in smaller amounts, is then the main component of the mother liquors and can be isolated from them by known methods, e.g. by evaporating the mother liquor and recrystallizing the residue until a product with a constant melting point is obtained. However, a mixture of epimers can be separated into individual epimers, however, it is preferable to use the mixture without separating it, and it is often advisable to use at least one recrystallization from a suitable solvent, purification by column chromatography or liquid chromatography under pressure, extraction or trituration in a suitable solvent. Such purification is carried out not to separate the epimers, but to remove impurities in the form of starting products and undesirable by-products. The stereochemical phenomena associated with both epimers have not been completely investigated, but it has been found that for a given compound both epimers exhibit the same type of activity , e.g. antibacterial activity. The new derivatives of 4"-deoxy-4"-aminoerythromycin A discussed in this description have in vitro activity against various Gram-positive microorganisms, rip.7 Staphylococcus aureus and Streptococcus pyogenes, and against some microorganisms. Gram-negative organisms, such as spherical or ellipsoidal microorganisms (cocci). Their in vitro activity against various microorganisms in the cerebrocardiac infusion environment is easily demonstrated by tests carried out using the well-known double dilution method. This activity makes these compounds useful for topical application in the form of ointments, creams, etc., for sterilization, e.g., of objects in the patient's room, and as microbicides on a technical scale, e.g., for disinfecting water and mud, and for preservation of paints and wood. When used in vitro, e.g. When administered topically, it is often advantageous to use these compounds with a pharmacologically acceptable carrier such as a vegetable or mineral oil or an emollient cream. They can also be dissolved or dispersed in liquid carriers or solvents, such as water, alcohol, glycols or mixtures thereof, or other pharmacologically acceptable inert substances, i.e., having no harmful effect on the active substance. In such preparations, the content of the active substance is usually 0.01-10% by weight in relation to the entire preparation. Many compounds according to the invention and their acid addition salts also show activity in vivo, when administered orally and/or parenterally to animals. , including humans, against Gram-positive and some Gram-negative microorganisms. Their in vivo activity is more limited for organisms susceptible to the action of these compounds and is determined by conventional methods by infecting mice with essentially body weight with the tested microorganism and then administering the tested compound orally or subcutaneously to the mice. In practice, these studies are carried out in such a way that a group of e.g. 10 mice is infected by administering intraperitoneally appropriately diluted cultures of the microorganism, containing 1-10 times greater the concentration of the microorganism from the LDioo concentration, i.e. from the lowest concentration necessary to obtain 100% mortality in mice. At the same time, control trials are carried out in which mice receive an infectious culture in lower dilutions in order to determine any possible deviations in the virulence of the tested microorganism. . The tested compound is administered 0.5 hour after infection and again after 4, 24 and 48 hours. The surviving mice are kept within 4 days of the last treatment and live individuals are counted. When used in vivo, the new compounds can be administered orally or parenterally, e.g. by subcutaneous or intramuscular injection, at daily doses of approximately 1-200 mg/ kg, preferably about 5-100 mg/kg, and especially about 5-50 mg/kg. Carriers for parenteral injection may be aqueous carriers such as water, isotonic saline, isotonic dextrose solution or Ringer's solution, or non-aqueous carriers such as fatty oils of vegetable origin, e.g. cottonseed oil, peanut oil, corn oil or sesame oil, or dimethyl sulfophlene, as well as other carriers which, in the doses used, do not affect the pharmacological action of the active substance and are not toxic, e.g. glycerin, propyl glycol and sorbitol. It is also possible to prepare agents which are converted into solutions immediately before use. Such agents may contain liquid diluents, e.g. given pharmacological properties. These compounds can also be; mix with various pharmacologically acceptable inert carriers, including solid diluents, aqueous, non-toxic organic solvents, and give them the form of capsules, tablets, lozenges, tablets, dry mixtures, suspensions, solutions, elixirs and solutions or io suspensions for parenteral administration. In these preparations, the active substance constitutes approximately 0.5-90% by weight. Example I. 2'-acetyl-4"-deoxy-4"-ketoerythromycin oxime A. 10.8 g of 2 are added to 500 ml of methanol '-acetyl-4"-deso-15 oxy-4"-ketoerythromycin A, 1.94 g of hydroxylamine hydrochloride and 11.0 g of barium carbonate and the obtained suspension: stirred at room temperature for 3.5 hours, then then filtered and the filtrate evaporated under reduced pressure. The foamy residue is dissolved in ethyl acetate and washed with water at a pH of 9.5, the organic phase is separated, dried over sodium sulfate and evaporated under reduced pressure to obtain 10.6 g of the desired product. NMR (S CDC13): 3.33 (3H)s, 2.30 (6H)s and 2.06 (3H)s. 25 Example. 2'-acetyl-4"-deoxy-4"-ketoerythromycin A O-acetyloxime. To a solution of 330 mg of 2'-acetyl-4"-deoxy-4"-ketoerythromycin A oxime in 30 ml of ethyl acetate is added with stirring 64 .2 microliters of acetic anhydride and stir overnight at room temperature, then add another 15.8 microliters of acetic anhydride and 23.4 microliters of triethylamine and stir for 4 hours. The reaction mixture is poured into water, alkalinized to pH 9.0, the organic layer is separated, dried over sodium sulfate and evaporated under reduced pressure to obtain 300 mg of the desired product. NMR (Sy, CDCh): 3.38 (3H)s, 2.25 (6H)s, 2.20 (3H)s, 2.05 (3H)s ~ il.56(3H)s. In a similar way, using instead of 2'-acetyl-4/-deoxy-4,,-ketoerythromycin A oxime, 2'-propionyl-4"-deoxy-4"-ketoerythromycin A oxime and 4"-deoxy-4 oxime "-ketoerythromycin A, the corresponding O-acetyl derivatives are prepared. Example -III. 2'-acetyl-4"-deoxy-4"-aminoerythromycin A. 14.0 g of O-acetyloxime 2'-acetyl-4"-deoxy-4"-ketoerythromycin A and 60 g of Raney nickel washed with isoprop - nolem is stirred in 400 ml of isopropanol in a hydrogen atmosphere under reduced pressure of 9331 Pa for 50 nights at room temperature, then the catalyst is filtered off and the filtrate is evaporated. The white, foamy residue is dissolved in 400 ml of isopropanol, mixed with 50 g of Raney nickel freshly washed with isopropanol and hydrogenated overnight at room temperature, 55 under an initial hydrogen pressure of 9331 Pa. Then the catalyst is filtered off and the filtrate is evaporated to dryness under reduced pressure, obtaining 8.1 g of the desired product. Example IV. In a manner analogous to that described in Example 3, using appropriate O-acetyloximes. compounds of formula 4 are prepared, in which R3 and R4 represent hydrogen atoms and Ri represents a hydrogen atom or a propionyl group. *" Example Overnight, and then the solvent is evaporated under reduced pressure. The foamy residue is treated with a mixture of 50 ml of chloroform and 50 ml of water, the aqueous layer is alkalinized to pH 9.5 and the layers are separated. Fresh water is added to the organic layer and acidified to a pH of 4.0, after which the pH of the acidic aqueous layer is gradually adjusted to 5, * 6, 7, 8 and 9 with a base and at each of these pH values the solution is extracted with chloroform. The extracts at pH values 6 and 7 contain the main part of the product, they are combined and at pH 4 fresh water is added, the pH of the aqueous layer is adjusted successively to 5, 6 and 7 and at each of these values it is extracted with chloroform. The extract at pH 6 was dried over sodium sulfate and evaporated, obtaining 249 mg of product in the form of a mixture of both epimers. NMR (S, CDCb): 3.30 (1H)s, 3.26 (2H)s, 2.30 (6H)s and 1.46 (3H)s. In a similar way, by solvolize 2'-propionyl-4"- -deoxy-4"-aminoerythromycin A, 4"-deoxy-4"-aminoerythromycin A is prepared. Example VI. 4"-deoxy-4"-aminoerythromycin A. To a solution of 3.0 g of 4'-deoxy-4//-ketoerythromycin A in 30 ml of methanol, 3.16 g of anhydrous ammonium acetate are added with stirring in a nitrogen atmosphere and after 5 minutes - 188 mg of sodium cyanoborohydride are injected into the mixture with 5 ml of methanol and stirred overnight at room temperature. The obtained light yellow solution is poured into 300 ml of water, adjusted to pH 6.0 and then extracted successively at pH values 6, 7, 7.5, 8, 9 and 10, each time using 125 ml of diethyl ether. The extracts at pH values 8, 9 and 10 are combined, washed with 125 ml of fresh water, the aqueous layer is separated and extracted with 100 ml of ether at pH 7, 100 ml of ethyl acetate at pH 7, 100 ml of ether at pH 7.5, 100 ml of ethyl acetate at pH 7.5 and 100 ml of ethyl acetate at pH 8, 9 and 10. The extracts obtained using ethyl acetate at pH 9 and 10 are combined and washed with a saturated sodium chloride solution, dried over sodium sulfate and evaporated under reduced pressure, obtaining 30 mg of an epimeric product mixture with the consistency of an ivory-colored foam. Example VII. 4,/-deoxy-4"-aminoerythromycin A (single epimer). A solution of 10.0 g of the epimer mixture of 2'-acetyl-4"-deoxy-4"-aminoerythromycin A in 150 ml of methanol is stirred under a nitrogen atmosphere at room temperature for 72 hours, then the solvent is evaporated under reduced pressure and the residue is dissolved with stirring in a mixture of 150 ml of water and 200 ml of chloroform. The aqueous layer is discarded, fresh water is added, the pH of the aqueous layer is adjusted to 5 and separates the organic layer. The pH of the aqueous phase is adjusted successively to 5.5, 6, 7, S and 9 and at each of these values 100 ml of fresh chloroform is extracted. The extracts at pH values 6, 7 and 8 were combined, washed successively with water and a saturated sodium chloride solution, dried over sodium sulfate and the solvent was evaporated under reduced pressure. 2.9 g of a mixture of 4"-deoxy-4"-aminorithromycin A epimers are obtained. A sample of 1.9 g of this mixture is triturated with diethyl ether, causing crystallization of part of the undissolved foamy product. The solid substance is filtered off and dried, obtaining 10-67 mg of one epimer of 4-deoxy-4-aminoerythromycin A, melting point 140-147 °C. Example VIII. 6,9-hemiketal 11-acetyl-4"-deoxy-4"-aminoerythromycin A. 5 To a solution of 4.4 g of 6,9-hemiketal 11-acetyl-4"-deoxy-4"-ketoerythromycin A and 4.38 g of ammonium acetate in 75 ml of methanol, 305 mg of 85% sodium cyanoborohydride are added, stirred overnight at room temperature and poured into 300 ml of water, and then 10 250 ml of chloroform are added. The aqueous layer is alkalinized to a pH value of 9.8 and the organic layer is separated. The aqueous layer is extracted again with chloroform and the chloroform solutions are combined, dried over sodium sulfate and evaporated. The foamy residue is dissolved with stirring in 125 ml of water and 125 ml of fresh chloroform, the pH value of the solution is adjusted to 4.9, the organic layer is separated and discarded and the pH value of the aqueous layer is adjusted successively to 5, 6, 7 and 8,' extracting at each of these pH values with fresh chloroform. 20 The extracts obtained at pH values 6 and 7 are combined, washed with a saturated sodium chloride solution, dried over sodium sulfate and the solvent is evaporated. 1.72 g of the desired product are obtained in the form of white foam. This product is dissolved in as little diethyl ether as possible and hexane is added until turbidity occurs. The crystalline precipitate is filtered off and dried, obtaining 1.33 g of product with a melting point of 204.5-206.5°C. NMR (S, CDC13): 3.31 (2H)s, 3.28 (1H)s, 2.31 (6H)s, 2.11 (3H)s and 1.5 (3H)s. 30 Example IX. In a manner analogous to that described in Example 8, using the appropriate 4"-deoxy-4"-ketoerythromycin A and isopropanol instead of methanol, compounds of formula 3 are prepared, in which R3 is hydrogen, and Ri and R2 have the following meanings: Ri R2 CH3C(0)- CH3C(0)- CH3C(0)- CH3CH2C(0)- CH3CH2C(0)- CH3CH2C(0)- CH3CH2C(0)- CH3C{0)- 40- Example X. 11.12 -2'-acetyl-erythromycin A 6,9-hemiketal carbonate. To a solution of 13.2 g of erythromycin A 6,9-hemiketal 11,12-carbonate (US Pat. No. 3,417,077) in 150 ml of benzene are added with 1.8 ml of acetic anhydride 45 and stirred at room temperature for 1.5 hours, then poured into 200 ml of water and the aqueous layer is made alkaline. to a pH value of 9.0. The benzene layer is separated, dried over sodium sulfate and evaporated under reduced pressure to obtain 15.3 g of a foamy white product 50. This product is triturated with 50 ml of diethyl ether, causing crystallization, then filtered and dried, obtaining 12.6 g of pure product with a melting point of 224.5-228.5 °C. NMR (<5, CDCl3): 3.36 (3H)s, 2.30 (6H)s 2.06 (3H)s and 1.61 (3H)s. 55 In a similar manner, using an equivalent amount of propionic anhydride instead of acetic anhydride, 11,12-carbonate of 2'-propionyl-erythromycin 6,9-hemiketal is prepared. Example XI. 4"-deso-60 oxy-4"-aminoerythromycin A 11,12-carbonate 6,9-hemiketal.. Up to 189 g of 4"-deoxy-4"-ketoerythromycin A 11,12-carbonate in 1200 ml of methanol are added with stirring at room temperature to 193 g of ammonium acetate and after 5 minutes the solution is cooled to a temperature of about -5°C and within 45 minutes 13.4 g of 116 228 11 85% sodium cyanoborohydride in 200 ml of methanol. Then the cooling bath is removed and stirred at room temperature overnight, then the concentration is reduced under reduced pressure to a volume of 800 ml and, while stirring, poured into a mixture of 1800 ml of water and 900 ml of chloroform. The pH of the mixture, which is 6.2, is adjusted to 4.3 with 6N hydrochloric acid and the organic layer is separated, mixed with 1 liter of water and alkalinized to a pH of 9.5. The organic layer is then separated, dried over sodium sulfate and evaporated under reduced pressure. The white, foamy residue is dissolved in a mixture of 1 liter of water and 500 ml of ethyl acetate and acidified to a pH of 5.5. The organic layer is separated and the aqueous layer is gradually alkalinized to pH 9.5, extracted at intermediate pH values with fresh ethyl acetate in 500 ml portions. The extract obtained at pH 9.5 is dried over sodium sulfate and evaporated to dryness under under reduced pressure, obtaining 130 g of residue. 120 g of this foamy residue are dissolved in a mixture of 1 liter of water and 1 liter of methylene chloride, the pH of the aqueous layer is adjusted to 4.4, 4.9 and 9.4, extracting at each of these values 1 liter of fresh methylene chloride. The extract at a pH of 9.4 is dried over sodium sulfate and evaporated under reduced pressure, obtaining 32 g of a white foam product. After recrystallization from 250 ml of acetone-water mixture (1:1 by volume), 28.5 g of crystalline epimers are obtained. NMR 100 Mz (S, CDCh): 5.20 (1H)m, 3.37 (13)Hs, 3.34 (1,5H)s, 2.36 (6H)s, 1.66 (3H)si 1.41 (3H)s.Example XII. Separation of 11,12-carbonate 6,9-hemiketal epimers of 4"-deoxy-4"-aminoerythromycin mg of the epimer mixture obtained as described in example Fractions 14-21 are combined, concentrated to a volume of approximately 50 ml, 50 ml of water are added and the pH is adjusted to 9.0. The organic layer is then separated, dried over sodium sulfate and evaporated to give 106 mg of residue as a white foam. The product is triturated with diethyl ether to cause crystallization. The product is stirred at room temperature for 1 hour. filters off the crystalline product and dries it, obtaining 31.7 g of product with a melting point of 194-196 °C. NMR 100 Mz (S, CDCh): 5.24 (lH)d, 5.00 (lH)t, 3.40 ( 3H)s, 2.40 (6H)s, C66(3H)s and 1.40 (3H)s. % Fractions 24-36 are also combined and processed in the manner described above, obtaining 47.1 mg of a product with the consistency foam and white in color, identical to the product obtained as described in Example XVII. Example 300 ml of isopropanol are added to 10.7 g of ammonium acetate while stirring at room temperature and after 5 minutes the addition is started for 30 minutes. 747 mg of sodium cyanoborohydride in 130 ml of isopropanol are then stirred at room temperature for night. The obtained pale yellow solution is poured into 1100 ml of water and 400 ml of diethyl ether is added, acidified to a PTT value of 4.5 and the ether layer is separated. The aqueous layer 12 is alkalinized to a pH of 9.5 and extracted with 2 portions of 500 ml of chloroform, the extracts are combined, dried with sodium persulfate and evaporated to obtain 7.5 g of a foamy yellow residue, Pb recrystallized from ether 5 diethyl, 1.69 g of product is obtained, which is further processed in the same way as the mother liquor. The mother liquor is treated with 75 ml of water, the pH value is adjusted to 5.0, the ether layer is separated, 75 ml of fresh ether is added again, the pH is adjusted pH to 5.4, separate the ether layer, add ethyl acetate and alkalize to pH 10. The basic aqueous layer is extracted with 2 portions of 75 ml of ethyl acetate, the first extract is dried over sodium sulfate and evaporated to dryness. ,, obtaining 1.96 g of a foamy residue. This product is added to a mixture of 75 ml of water and 50 ml of diethyl ether, the pH is adjusted to 5.05, the ether layer is separated and the aqueous layer is gradually adjusted to the pH of 5.4, 6 .0, 7.05 and 8^0, extracting at each of these values with 50 ml of fresh diethyl ether. Finally, it is basified to a pH of 9.7 and the aqueous layer is extracted with 50 ml of ethyl acetate. The ether extract obtained at a pH value of 6.0 is combined with 75 ml of water and alkalinized to a pH value of 9.7. separates the ether layer, dries it and evaporates it under reduced pressure, obtaining 460 mg of a foamy white residue, NMR 100 Mz (<5, CDCh): 5.20 (1H)t" 3.43 (2H) )s, 3.40 (lH)s, 2.38 (6H)s, 2.16 (3H)s, 1.70- (3H)s and 1.54 (3H). This analysis indicates that the product is an epimer of 11,12-carbonate 6,9-hemiketal of 2'-acetyl-4"-deoxy-4"-aminoerythromycin A. 30 The above-mentioned 1.69 of the product obtained after the first crystallization dissolves in mixture of 75 ml of water and 75 ml of diethyl ether, the pH value of the solution is adjusted to 4.7, the ether and aqueous layers are separated, the layer is extracted with 75 ml of fresh ether at pH 35 of 5.05 and 5.4 and with 2 portions of 75 ml of acetate ethyl see pH value 9.7. The combined ethyl acetate solutions were dried over sodium sulfate and evaporated under reduced pressure to obtain 1.26 g of a white foamy residue. After recrystallization 40, 411 mg of product are obtained, melting with signs of decomposition at temperatures of 193-196 °C. The mother liquor is evaporated to dryness, the residue is dissolved in hot ethyl acetate and the solution is left to crystallize overnight at room temperature, the crystalline precipitate is filtered off and dried, obtaining an additional portion of the product in the amount of 182 mg. This product melts with symptoms of decomposition at a temperature of 198-202°C. NMR 100 Mz (S, CDCh): 5.10 (1H)t, 3.34 (2H)s, 3.30 (1H)s, 2.30 (6H)s, 2.08 (3H)s, 1 .62 (3H)s and 1.48 (3H)s. This analysis indicates that product 50 is an epimer of 11,12-carbonate, 2'-acetyl-4"-deoxy-4"-aminoerythromycin A. In a similar manner, using 6,9-hemiketal 11,12-carbonate 2' as the starting product -propionyl-4"-deoxy-4"-ketoerythromycin 11,12-carbonate 6,9-hemi-55 ketal 2A-propionyl-4''-deoxy-4"-aminoerythromycin A and 11,12-carbonate 2 '-propionyl-4"-deoxy-4"-aminoerythromycin A. Example 14. Solution of 400 mg of 11,12-carbonate 60 ml of methanol is stirred overnight at room temperature, poured into 100 ml of water, 50 ml of ethyl acetate is added, the mixture is alkalinized to pH 9.5 and the organic phase is separated. Then the aqueous layer is extracted again with 50 ml of fresh ethyl acetate, both extracts are combined, dried over sodium sulfate and evaporated to obtain - / * 116 228 13 h 392 mg of a white foamy product. This product is dissolved in diethyl ether and crystallized at room temperature by rubbing the wall of the vessel with a glass rod. After 30 minutes, the crystalline precipitate is filtered off and dried, obtaining 123 mg of product, which is identical to the product prepared in Example 16. 100 Mz NMR (S, CDCh): 3.26 (3H)s, 2.32 (6H)s, 1.61 (3H)s, and 1.44 (3H)s. This analysis indicates that this product is one epimer of 11,12-carbonate of 4/-deoxy-4"-aminoerythromycin A. After crystallization of the above-mentioned compound, the mother liquor is evaporated to dryness, obtaining 244 mg of a foamy product, identical to the product prepared. prepared as described in Example described in Example XXII, by methanolizing the 11,12-carbonate of 6,9-hemiketal 2'-propionyl-4''-deoxy-4''-aminoerythromycin A, 11,12-carbonate 4"-deoxy- 4"-amino-erythromycin A and 11,12-carbonate of 6,9-hemiketal of 4"-deoxy-4"-aminoerythromycin A. Example 16. 8 g of epimeric mixture of 11,12-carbonate 4/-deoxy-4 /,-aminoerythromycin A from the non-crystalline product described in Example XI is dissolved in 50 ml of diethyl ether and crystallized by rubbing the wall of the vessel with a glass rod. After 20 minutes, the crystalline product is filtered off and dried, obtaining 1 91 g of product with a melting point of 198.5-200 °C. NMR 100 Mz (d, CDCh): 3.26 (3H)s, 2.30 (6H)s, 1.61 (3H)s and 1.45 (3H)s. The results of the analysis indicate that this crystalline product is one epimer of 4"-deoxy-4"-aminoerythromycin A 11,12-carbonate and is identical to the compound prepared in Example XIV. Example XVII. 1.0 g of the epimer obtained as described in Example 16 is dissolved in 20 ml of acetone and heated on a steam bath until it boils, then 25 ml of water is added and the resulting solution is stirred at room temperature. After 1 hour, the precipitate formed is filtered off, obtaining 581 mg of product with a melting point of 147-149°C. NMR 100 Mz (S, CDCh): 5.12 (1H)d, 3.30 (3H)s, 2.30 (6H)s, 1.62 (3H)s, and 1.36 (3H)s. The results of the analysis indicate that the product is one epimer of 11,12-carbonate of 6,9-hemiketal of 4"-deoxy-4"-aminoerythromycin A and it is identical to the epimer obtained from fractions 24-36 in Example XII. Example 18 . 4"-deoxy-4"-aminoerythromycin A. 50 20 g of 4"-deoxy-4"-ketoerythromycin A, 31.6 g of ammonium acetate and 10 g of 10% palladium on charcoal are mixed in 200 ml of methanol and shaken at room temperature temperature overnight in a hydrogen atmosphere with an initial pressure of 466.5 Pa. The spent catalyst is then filtered off, the filtrate is evaporated to dryness under reduced pressure and the residue is extracted with water and chloroform at a pH of 5.5. The organic layer is separated, dried over sodium sulfate and evaporated to dryness under reduced pressure to give 19 g of a white foamy residue. The residue is triturated with 150 ml of diethyl ether at room temperature for 30 minutes and the precipitate is filtered off, obtaining after drying 9.45 g of one epimer, which does not differ from the product prepared as described in Example 7. After crystallization of the product, the filtrate 65 is evaporated to dryness, obtaining 6.89 g of the product being the second epimer and containing a certain amount of impurities. Example XIX. 4"-deoxy-4"-aminoerythromycin. 2 g of 4-deoxy-4-ketoerythromycin A, 3.1 g of ammonium acetate and 2.0 g of Raney nickel in 50 ml of methanol are shaken overnight at room temperature in a hydrogen atmosphere under initial pressure. 466.5 Pa, then 3.16 g of ammonium acetate and 2.0 g of Raney nickel are added and hydrogenation is continued for another 5 hours. Then the mixture is filtered, the filtrate is evaporated to dryness under reduced pressure, the residue is added to the mixture of water and chloroform with stirring and the pH of the mixture, which is 6.4, is adjusted to 5.5. The aqueous phase is separated, basified to a pH of 9.6, extracted with fresh chloroform, the extract dried over sodium sulfate and evaporated under reduced pressure. 1.02 g of product with the consistency of yellow foam is obtained. This product contains mainly an isomer whose configuration at the 4" position is different from the configuration at this position in the compound prepared as described in Example 7. Example XX. 2'-acetyl-4"-deoxy-4"-aminoerythromycin B. To a solution of 4.5 g of 2'-acetyl-4"-deoxy-4"-ketoerythro-^mycin B (St. Zj. Am. patent no. 3,884,903) in 45 ml of isopropanol is added with stirring in an atmosphere of nitrogen 4, 66 g of dry sodium acetate and after 10 minutes, 376 mg of sodium cyanoborohydride are rinsed into the mixture with 10 ml of isopropanol and stirred at room temperature overnight. The obtained light yellow solution is poured into 400 ml of water and the pH value of the solution is adjusted. to 6.0, then this solution is extracted successively at pH values 6, 7, 7.5, 8, 9 and 10, using 250 ml of diethyl ether for each extraction. The extracts at pH values 8, 9 and 10 are combined is washed with 250 ml of fresh water. The separated aqueous layer is extracted with 100 ml of ether at pH = 7, 100 ml of ethyl acetate at the same pH, 100 ml of ether and then 100 ml of ethyl acetate at pH = = 7.5 and 100 ml of ethyl acetate at pH values 8, 9 and 101. The ethyl acetate extracts obtained at pH values 9 and 10 are combined, washed with a saturated sodium chloride solution, dried over sodium sulfate, and the solvent is evaporated under reduced pressure to obtain a mixture epimers of 2'-acetyl-4"-deoxy-4"-aminoerythromycin B in the form of a cream-colored foamy product. In a similar manner, 4"-deoxy-4"-ketoerythromycin B is prepared "-aminoerythromycin B. Example XXI. 4'-deoxy-4,1-aminoerythromycin B. A solution of 4.34 g of 2'-acetyl-4"-deoxy-4"-aminoerythromycin B in 100 ml of methanol is stirred at room temperature overnight, and then the solvent is evaporated under reduced pressure and the foamy residue is treated with a mixture of 100 ml of chloroform and 100 ml of water. The pH of the aqueous layer is adjusted to 9.5, the organic layer is separated, mixed with water and acidified to a pH of 4.0. The pH of the aqueous layer is then adjusted to 5, 6, 7, 8 and 9 by adding a base and extracted with fresh chloroform at each of these values. The extracts at pH values 6 and 7, containing the main part of the product, are combined and treated at pH 4 with fresh water. The pH of the aqueous layer is again adjusted to 5, 6 and 7 and at each of these values 15. tosci extracts the solution with fresh chloroform. The extract at pH = 6 is dried over sodium sulfate and evaporated to obtain a mixture of epimers of 4"-deoxy-4"-aminoerythromycin B. Example XXII. Aspartic acid addition salt of 11,12-carbonate of 6,9-hemiketal 4"-deoxy-4"-aine-erythromycin A. This compound is prepared by adding 1.0 g of 11,12-carbonate 6,9-hemiketal 4"-deoxy-4"-amino- erythromycin A in 6 ml of acetone, heated to 40°C, 20 ml of water and then 175 mg of L-aspartic acid are added, then the mixture is kept at reflux for 1.5 hours, filtered while hot and acetone is evaporated from the filtrate. From the residue, 1.1 g of a white solid product is obtained by freezing. Example XXIII. Dihydrochloride of 11,12-carbonate of 6,9-hemiketal of 4"-deoxy-4"-aminoerythromycin A. Do 7, 58 g of 6,9-hemiketal 4"-deoxy-4"-aminoerythromycin 11,12-carbonate in 50 ml of anhydrous ethyl acetate, 20 ml of 1N solution are added. HCl in ethyl acetate and the mixture is evaporated to dryness under reduced pressure. and triturate the residue with ether to obtain the desired compound. . In a similar manner, other compounds prepared according to the invention are converted into their addition salts with two molecules of a monobasic acid. Example XXIV. Hydrochloride of 11,12-carbonate of 6,9-hemiketal of 4/-deoxy-4,,-aminoerythromycin. In a manner analogous to that described in Example XXIII, but using 10 ml of 1N solution of hydrogen chloride in ethyl acetate, the above-mentioned monohydrochloride is prepared. ester. Similarly, other addition salts of the compounds prepared according to the invention are prepared, containing 1 mole of monobasic acid per 1 mole of erythromycin derivative. Patent claims 1. Method for preparing new derivatives of 4"-deoxy-4-aminoerythromycin A of the general formula 3a, in which Ri and R2 denote a hydrogen atom or an alkanoyl radical with 2^-3 carbon atoms, R3 denotes a hydrogen atom, or R2 and R3 together denote a -C(O)- group, when R' denotes a CH group, R denotes a bond to a carbon atom to which R' is attached, or when R' is =0, R is hydrogen, wherein when R2 is hydrogen, R is also hydrogen and pharmaceutically acceptable acid addition salts thereof, characterized in that the compound having formula Ib, in which R, Ri, R2 and R3 have the meanings given above, Y is the group =N-OH or =N-OCOCH3, is subjected to catalytic reduction, and then the obtained compound is optionally converted into an acid addition salt. 2. A method for preparing new derivatives of 4"-desolcsy-4-aminoerythromycin A of the general formula 3a, in which Ri and R2 denote hydrogen atoms, R3 denotes a hydrogen atom, R' denotes =0, R denotes a hydrogen atom, and their pharmacology ceutically acceptable acid addition salts, characterized in that the compound of formula Ib, in which R, R' and R3 have the meanings given above, Ri and R2 denote alkanoyl radicals with 2-3 carbon atoms, Y denotes the group =N- OH or =N-OCOCH3, undergoes catalytic reduction; and then the obtained compounds are hydrolyzed and optionally converted into acid addition salts. 6 228 16 3. Method for preparing new derivatives of 4"-deoxy-4-aminoerythromycin A with the general formula 3a, in which Ri and R2 are alkanoyl radicals with 2-3 carbon atoms, R3 is a hydrogen atom, when R' is a CH group, R5 is a bond with the carbon atom to which R' is attached or when R' is = 0, R is hydrogen, and pharmaceutically acceptable acid addition salts thereof, characterized in that the compound of formula Ib in which R, R' and R3 have the meaning given above, Ri and R2 denote hydrogen atoms, Y denotes the group - =N-OH or =N-OCOCH3, is subjected to catalytic reduction, and then the obtained compounds are acylated and optionally converted into addition salts with acids. 4. Method for preparing new derivatives of 4"-deoxy-15-4-aminoerythromycin A of the general formula 3a, in which Ri and R2 represent a hydrogen atom or an alkanoyl radical with 2-3 carbon atoms, R3 represents a hydrogen atom or R2- and R3 together represent a -C(O)- group when R' is an OH group, R is a bond to the carbon atom to which R' is attached or when R' is =0, R is hydrogen, wherein when R2 denotes a hydrogen atom, R also denotes a hydrogen atom and pharmaceutically acceptable acid addition salts thereof, characterized in that the compound of formula Ib in which R, R', Ri, R2 and R3 have the meanings given above, Y denotes an oxygen atom , is subjected to condensation with an ammonium salt of an alkanecarboxylic acid, the compound of formula Ib produced in situ, in which Y is the =NH group, is subjected to reduction with a metal hydride, and then the obtained compound is optionally transformed into an addition salt, with acid. 5. A method for preparing new derivatives of 4"-deoxy-4-aminoerythromycin A of the general formula 3a, in which Ri and R2 are hydrogen atoms, R3 is a hydrogen atom, R' is =0, R is a hydrogen atom, and their pharmaceutical 35 ceutically acceptable acid addition salts, characterized in that the compound has the formula Tl, in which R, R' and R3 have the meanings given above, Ri and R2 denote alkanoyl radicals with 2-3 carbon atoms, Y denotes an oxygen atom. is subjected to condensation with the ammonium salt of an alkane-40 carboxylic acid, the compound of formula Ib produced in situ, in which Y is the group =I^H, is subjected to reduction with a metal hydride, and then the obtained compound is hydrolyzed and optionally transformed into an acid addition salt. 4 45 6. Method for preparing new derivatives of 4"-deoxy-4-aminoerythromycin A of the general formula 3a, in which Ri and R2 are alkanoyl radicals with 2-3 carbon atoms, R3 is a hydrogen atom, when R' is a group, R is a bond to the carbon atom to which R' is attached or when R' is =0, R is a hydrogen atom, and pharmaceutically acceptable acid addition salts thereof, characterized in that the compound of formula Ib , in which R, R' and R3 have the meanings given above, Ri and R2 represent hydrogen atoms, Y represents an oxygen atom, is subjected to condensation with an ammonium salt of an alkanecarboxylic acid, the compound of formula Ib produced in situ, wherein Y is =NH group, is reduced with metal hydride, and then the obtained compound is acylated and optionally converted into an acid addition salt. 60 7. Method for preparing new derivatives of 4/-deoxy-4-aminoerythromycin A with the general formula 3a, in which Ri and R2 represent a hydrogen atom or an alkanoyl radical with 2-3 carbon atoms, R3 represents a hydrogen atom, or Ri and R3 together denote the group -C(O)- when R' denotes the 6S OH group, R denotes a bond to the carbon atom to which R' is attached or when R' denotes =0, R denotes a hydrogen atom, provided that when R2 represents a hydrogen atom, R also represents a hydrogen atom and pharmaceutically acceptable acid addition salts thereof, characterized in that the compound of formula Ib in which R, R', Ri, R2 and R3 have the above-mentioned meanings, Y means an oxygen atom, is subjected to condensation with an ammonium salt of an alkanecarboxylic acid, the compound of formula Ib produced in situ, in which Y is the =NH group, is subjected to reduction by catalytic hydrogenation, and then the obtained compound is optionally transformed into an addition salt with acid. 8. A method for preparing new derivatives of 4"-deoxy-4-aminoerythromycin A of the general formula 3a, in which Ri and R2 denote hydrogen atoms, R3 denotes a hydrogen atom, R' means =0, R denotes a hydrogen atom, and their pharmacology ceutically acceptable acid addition salts, characterized in that the compound of formula Ib, in which R, R' and R3 have the meanings given above, Ri and R2 denote alkanoyl radicals with 2-3 carbon atoms, Y denotes an oxygen atom, undergoes condensation with the ammonium salt of an alkanecarboxylic acid, the compound of formula Ib produced in situ, in which Y is the =NH group, is subjected to reduction by catalytic hydrogenation, and then the obtained compound is hydrolyzed and optionally transformed into an addition salt with acid. 9. Method for preparing new derivatives of 4"-deoxy-4-aminoerythromycin A with the general formula 3a, in which Ri and R2 are alkanoyl radicals with 2-3 carbon atoms, R3 is a hydrogen atom, when R' is an OH group, R is a bond to the carbon atom to which R' is attached, or when R' is =0, R is hydrogen, and pharmaceutically acceptable acid addition salts thereof, characterized in that the compound of formula Ib, wherein R, R ' and R3 have the meanings given above, Ri and R2 denote hydrogen atoms, Y denotes an oxygen atom, is subjected to condensation with the ammonium salt of an alkanecarboxylic acid, the compound of formula Ib produced in situ, in which Y is =NH, is reduced by catalytic hydrogenation, and then the obtained compound is acylated and optionally converted into an acid addition salt.NiCH-:)r Ac N(CH3,? 0CH3 PATTERN la R20 OCI-h WZCJR 2116 228 3'2 WZCiR 1b WZ0R 2a WZCfR 2a NH4OCOCH3 NaCNBHo SCHEME WZCR 3 PATTERN U SCHEME cont.116 228 NICH,), R20..R3o^ OCH, PATTERN 3a WZCJR 3 R ^N( CH3)2 a.TEMPLATE 5 PL PL PL PL PL

Claims (2)

1. Patent claims 1. Method for preparing new derivatives of 4"-deoxy-4-aminoerythromycin A of the general formula 3a, in which Ri and R2 represent a hydrogen atom or an alkanoyl radical with 2^-3 carbon atoms, R3 represents a hydrogen atom, or R2 and R3 together represent a -C(O)- group when R' represents a CH group, R represents a bond to the carbon atom to which R' is attached, or when R' represents =0, R represents a hydrogen atom, provided that when R2 represents a hydrogen atom, R also represents a hydrogen atom and pharmaceutically acceptable acid addition salts thereof, characterized by the compound of formula Ib in which R, Ri, R2 and R3 have the meanings given above, Y represents the group =N- OH or =N-OCOCH3, is subjected to catalytic reduction, and then the obtained compound is optionally converted into an acid addition salt. 2. A method for preparing new derivatives of 4"-desolcsy-4-aminoerythromycin A of the general formula 3a, in which Ri and R2 denote hydrogen atoms, R3 denotes a hydrogen atom, R' denotes =0, R denotes a hydrogen atom, and their pharmacology ceutically acceptable acid addition salts, characterized in that the compound of formula Ib, in which R, R' and R3 have the meanings given above, Ri and R2 denote alkanoyl radicals with 2-3 carbon atoms, Y denotes the group =N- OH or =N-OCOCH3, is subjected to catalytic reduction, and then the obtained compounds are hydrolyzed and optionally transformed into acid addition salts. 6 228 163. Method for preparing new derivatives of 4"-deoxy--4-aminoerythromycin A with general formula 3a, in which Ri and R2 are alkanoyl radicals with 2-3 carbon atoms, R3 is a hydrogen atom, when R' is a CH group, R5 is a bond with the carbon atom to which R' is attached or when R' is = 0 , R denotes a hydrogen atom, and pharmaceutically acceptable acid addition salts thereof, characterized in that the compound of formula Ib, in which R, R' and R3 have the meanings given above, Ri and R2 denote hydrogen atoms, Y denotes the group - = N-OH or =N-OCOCH3 is subjected to catalytic reduction, and then the obtained compounds are acylated and optionally converted into acid addition salts.4. A method for preparing new derivatives of 4"-deoxy-15-4-aminoerythromycin A of the general formula 3a, in which Ri and R2 represent a hydrogen atom or an alkanoyl radical with 2-3 carbon atoms, R3 represents a hydrogen atom, or R2- and R3 together represent ^ group -C(O)-, when R' is an OH group, R is a bond to the carbon atom to which R' is attached or when R' is =0, R is a hydrogen atom, wherein when R2 is a hydrogen atom , R also represents a hydrogen atom and pharmaceutically acceptable acid addition salts thereof, characterized in that the compound of formula Ib, in which R, R', Ri, R2 and R3 have the meanings given above, Y represents an oxygen atom, gives condensation with an ammonium salt of an alkanecarboxylic acid, the compound of formula Ib produced in situ, in which Y is the =NH group, is reduced with a metal hydride, and then the obtained compound is optionally transformed into an acid addition salt.5. A method for preparing new derivatives of 4"-deoxy-4-aminoerythromycin A of the general formula 3a, in which Ri and R2 are hydrogen atoms, R3 is hydrogen atom, R' is =0, R is hydrogen atom, and their pharmaceutical use permissible acid addition salts, characterized in that the compound has the formula Tl, in which R, R' and R3 have the meanings given above, Ri and R2 denote alkanoyl radicals with 2-3 carbon atoms, Y denotes an oxygen atom. is subjected to condensation with the ammonium salt of an alkane-40 carboxylic acid, the compound of formula Ib produced in situ, in which Y is the group =I^H, is subjected to reduction with a metal hydride, and then the obtained compound is hydrolyzed and optionally transformed into the addition salt with the acid. 4 456. Method for preparing new derivatives of 4"-deoxy-4-aminoerythromycin A with the general formula 3a, in which Ri and R2 are alkanoyl radicals with 2-3 carbon atoms, R3 is a hydrogen atom, when R' is a group, R is a bond with the carbon atom to which R' is attached or when R' is =0, R is hydrogen, and pharmaceutically acceptable acid addition salts thereof, characterized in that the compound of formula Ib, wherein R, R' and R3 have the meaning given above, Ri and R2 denote hydrogen atoms, Y denotes an oxygen atom, is subjected to condensation with the ammonium salt of an alkanecarboxylic acid, the compound of formula Ib prepared in situ, in which Y is the =NH group, is reduced using with the help of metal hydride, and then the obtained compound is acylated and optionally converted into an acid addition salt. 607. Method for preparing new derivatives of 4/-deoxy-4-aminoerythromycin A with the general formula 3a, in which Ri and R2 are hydrogen or an alkanoyl radical with 2-3 carbon atoms, R3 is a hydrogen atom, or Ri and R3 together represent a -C(O)- group, when R' is a 6S OH group, R is a bond to a carbon atom to which it is116 228 17 18 attached R' or when R' is =0, R is hydrogen, wherein when R2 is hydrogen, R is also hydrogen and pharmaceutically acceptable acid addition salts thereof, characterized in that the compound of formula Ib , in which R, R', Ri, R2 and R3 have the meanings given above, Y is an oxygen atom, is subjected to condensation with an ammonium salt of an alkanecarboxylic acid, the compound of formula Ib produced in situ, in which Y is the group = NH is reduced by catalytic hydrogenation, and then the obtained compound is optionally transformed into an acid addition salt.8. A method for preparing new derivatives of 4"-deoxy-4-aminoerythromycin A of the general formula 3a, in which Ri and R2 are hydrogen atoms, R3 is hydrogen atom, R' is =0, R is hydrogen atom, and their pharmaceutically acceptable acid addition salts, characterized in that the compound of formula Ib, in which R, R' and R3 have the meanings given above, Ri and R2 denote alkanoyl radicals with 2-3 carbon atoms, Y denotes an oxygen atom, undergoes condensation with the ammonium salt of an alkane carboxylic acid, the compound of formula Ib produced in situ, in which Y is the =NH group, is reduced by catalytic hydrogenation, and then the obtained compound is hydrolyzed and optionally converted into an acid addition salt. 9. Method for preparing new derivatives of 4"-deoxy-4-aminoerythromycin A with the general formula 3a, in which Ri and R2 are alkanoyl radicals with 2-3 carbon atoms, R3 is a hydrogen atom, when R' is an OH group, R is bond to the carbon atom to which R' is attached or when R' is =0, R is hydrogen, and pharmaceutically acceptable acid addition salts thereof, characterized in that the compound of formula Ib in which R, R' and R3 have the meaning given above, Ri and R2 denote hydrogen atoms, Y denotes an oxygen atom, is subjected to condensation with the ammonium salt of an alkanocarboxylic acid, the compound of formula Ib prepared in situ, in which Y is =NH, is subjected to reduction by hydrogen. catalytic reaction, and then the obtained compound is acylated and optionally converted into an acid addition salt. NiCH-:)r Ac N(CH3,? 0CH3 FORMULA la R20 OCI-h WZCJR 2116 228 3'2 WZCiR 1b WZ0R 2a WZCfR 2a NH4OCOCH3 NaCNBHo SCHEME WZCR 3 FORMULA U SCHEME cont.116 228 NICH,), R20.. R3o ^ OCH, MODEL 3a MODEL 3 R^ N(CH3)2 a. MODEL 5 PL PL PL PL PL