DE2550168B2 - 3 "" - N-monodesmethyl and 6 "-N3" "- N-didesmethyl derivatives of the antibiotic XK-62-2 and their salts with acids, processes for their preparation and their use in combating bacterial infections - Google Patents

Description

(H)

in which either R ¹ and R ^{2 are} each methyl groups (antibiotic XK-62-2) or one of the two radicals is a methyl group and the other is a hydrogen atom, in an inert solvent at temperatures from -20 to 100 ^° C. for 30 minutes 50 hours at pH 4 to OH

12 with iodine, potassium hexacyanoferrate (III), air or potassium permanganate and the resulting Product isolated and, if appropriate, the compound obtained is converted into a salt with an acid.

3. Use of the compounds according to claim 1 in combating bacterial infections.

The invention relates to the subject matter characterized in the preceding claims. The antibiotic XK-62-2 used according to the method and a method for its production are in the DT-PS 23 26 781 described.

3 4

The procedure according to the invention can be represented by the following reaction scheme:

Compound ll-a (XK-62-2)

reaction

Reaction II

NH, \ NH ₂
O

HO

Connection l-a

(3 "-N-Desmethyl

XK-62-2)

HO

Compound II-b (6'-N-Desmethyl-XK-62-2,
Gentamycin C ₁ ")

OH

Reaction III

Response IV

NH ₂ \ NH ₂ O

HO

Connection I-b

(6'-N, 3 "-N-didesmethyI

XK-62-2)

In the following, the invention is clarified in more detail with the aid of the above reaction scheme. In the demethylation reaction according to the invention, the partial reactions I, II, III and IV take place. the

Compound II-a is the antibiotic XK-62-2. This connection has one in each of the 6 'and 3 "positions Methylamino group. The compound I is used to prepare the compounds l-a and II-b with a Oxidizing agents of the type mentioned in claim 2 implemented.

The compounds I-a and l-b are new, valuable ones Antibiotics.

The compound l-a, 3'-N-desmethyl-XK-62-2 has an anti-antibiotic effect comparable to that of XK-62-2, however, a lower toxicity.

The compound II-b is as gentamycin Ci ,, from the US-PS 30 91 572 known.

If the compounds l-a or II-b with an oxidizing agent of the ArI mentioned in claim 2 reacted, the 6'-N or 3 "-N-methyl groups of the respective compound are formed with the Compound l-b eliminated.

The compound l-b, 6'-N, 3 "-N-Didesmethyl-XK-62-2 is also with its antibiotic effect XK-62-2 comparable and also has a lower toxicity than this known antibiotic.

In the demethylation of the compound II-: i to the Compounds I-a and II-b preferably take place in reaction I, since the 3 "-N-methyl group lighter than the 6'-N-methyl group is eliminated. Therefore, for the preparation of the compound I-a, it is preferable to get tired Reaction conditions applied, while comparatively energetic for the preparation of the compound II-b Reaction conditions are applied.

It should also be noted that a demethylation of the compound II-a according to the invention further demethylation of the compounds l-a and ll-b is inevitable. So one obtains a reaction gcmisch, which generally contains the compounds l-a, II-b and l-b, albeit the quantitative ratio of the individual compounds to one another varies depending on the reaction conditions. As mentioned earlier, is the yield of compound l-a is relatively high under mild reaction conditions, while in comparatively energetic reaction conditions the yield of compound II-b increases. After all, under will be very energetic reaction conditions the yield of compound l-b high and that of compound II-b very high small amount.

To prepare the compound l-b from the compound l-a after the reaction Ml are preferably relatively vigorous reaction conditions are used, since the elimination of the b'-N-methyl group doesn’t come off that easily.

On the other hand, for the preparation of the compound l-b from the compound II-b after the reaction IV are mild Sufficient reaction conditions.

To carry out the process according to the invention, the oxidizing agent] od. Potassium hydroxacyanoferrate (III), Air or potassium permanganate are used. Generally there will be 0.5 to 15.0 moles of oxidizing agent used per 1 mole of starting compound. When using air, the oxidizing agent becomes in Form of small bubbles by the reaction medium pearled.

As a solvent for carrying out the invention Reaction, solvents can be used in which the reaction participants and which do not react or react only to a very small extent with the reaction elements. For example can use water or mixtures of water Methanol, ethanol, tetrahydrofuran. Dimelhylaeetainid, Dimethylformamide, dioxane and Äthylenglykoldi methyläiher can be used.

The starting compounds are dissolved in a concentration of 4.5 to 50 millimolar in the solvent ■ '> The reaction according to the invention is de! oxidizing agent used at a pH before 4 to 12 carried out. Adjusting the pH Werli can be achieved by adding an appropriate acid or base. There are such acids or bases zi

κι use that neither a decomposition of the starting compounds or the demeihylicrten products noci cause a reduction of the oxidizing agent. Much more is an increase in the effect of the oxidation by means of desired. Examples of corresponding anorga

Nical acids are hydrochloric acid and black folic acid. Examples of corresponding organic acids are acetic acid and formic acid. Examples of corresponding bases are alkali metal hydroxides, Erdai potassium metal hydroxide c. Alkali metal carbonals, alkaline earths

-'ο metal carbonate c. Alkali metal oxides and alkali Alkaline earth metal salts of carboxylic acids.

The adjustment of the pH can either be carried out before the start of the reaction or during the reaction leads to be.

2 ~> The reaction according to the invention is at Tcmpcratu temperatures from -20 to 100 "C. preferably 0 to 70" C carried out during JO minutes to 50 hours.

The practical reaction conditions will be more desirable depending on the nature of the one

in the product and the oxidizing agent used chosen so that the highest possible yields achieved unc undesired reactions of other functional groups pen, such as the hydroxyl and amino groups dci starting compounds, are avoided.

For example, when using iodine, the preferred oxidizing agent for the reaction
the following reaction conditions are preferred: 0.7 to 10.1 mol, preferably 2.0 to 6.0 mol of iodine per 1 mol of XK-62-2; Reaction temperatures from -10 to 90 ^{0 C}

in preferably 40 to 60 ° C; and reaction times of 1 to: 24 hours, preferably 2 to 15 hours. Fernei are used to adjust the pH value 0.5 to 6.0 mol preferably 2.0 to 4.0 mol of a strong base or 5 (up to 25.0 mol; preferably 7.0 to 15 mol

• Γ) added weak base.

To carry out reactions II, III and IV as well as for the preparation of the compound l-b from the compound II-a, the following reaction conditions are preferred

1 to 13 moles, preferably 5 to 9 moles; 2 to 15 moles "> o preferably 6 to 11 moles; 0.7 to 10 moles, preferably

2 to 6 moles; or 3 to 15 mol, preferably 7 to 11 Mo Iodine per 1 mole of the starting compounds. The other reaction conditions are the same as for dei Reaction I.

ν. After the reaction has ended, the products are obtained in the usual way. For example, there is; Neutralized reaction mixture and concentrated under reduced pressure. The concentrate is put on a mi a column charged with a potassium exchange resin

hii set at which the non-restricted output connection fertilize and the reaction products are adsorbed. The column is washed with water and then cluicrt with 2.0 N aqueous ammonia solution. The Elua is concentrated, and the products are customary

h ^r, manner is isolated and purified, for example by column chromatography and Dünnsehichlchromalogra phic using lonenauslauscherharzcn Kicselgel, aluminum oxide and cellulose.

In Table I are the acute toxicity values (! .Dm) of the compounds II-a. I-a, ll-b and Ib for mice specified.

Table I.

LD50 mg / kg (iv)

Compound ll-a
Connection Ia

Table Il
Tribes

93
200

I. D _w mg / kg (iv)

Connection ll-b
Connection lb

88
138

Table II shows the antibacterial spectrum of the compounds II-a, I-a, II-b and I-b against various gram-positive and gram-negative bacteria indicated. The minimum inhibitory concentrations are through Determined dilution to twice the volume at pH 8.0.

Minimum inhibitory concentration (MIC; j.g / ml)

Verb, ll-a Verb. I-a Verb. II-b Verb, i-b

Pseudomonas aeruginosa
BMH 1

Staphylococcus aureus
ATCC 6538 I '

Bacillus subtilis

No. IO7O7
Proteus vulgaris

ATCC 6897
Shigella sonnei

ATCC 9290

Salmonella typhosa
ATCC 9992

Klebsieila pneumoniae
ATCC 10031

Escherichiu coli
ATCC 26

Escherichia coli
KY 8327

Escherichia coli
KY 8348

1.04 2.08 0.52 0.26 0.008 0.016 <0.004 <0.004 <0.004 0.008 <0.004 <0.004 0.065 0.13 0.033 0.033 0.13 0.13 0.065 0.065 0.033 0.065 0.016 0.033 0.016 0.033 0.008 <0.004 0.065 0.13 0.033 0.016 8.34 2.08 4.17 4.17 1.04 2.08 1.04 1.04

The microorganisms listed in Table II form Escherichia coli KY 8327 and KY 8348 intracellular adnyltransfcrase or acetyltransfcrase. Inactivate the former Bakiericnstamni! Kanamycins and genamycins by acnylation, while the latter inactivates gentamycins by acctylation.

Those produced by the process of the invention Compounds can optionally in pharmacologically acceptable, non-toxic salts with Acids are transferred. Examples of corresponding acids are inorganic acids, such as hydrochloric acid, Hydrobromic acid, hydriodic acid, sulfuric acid, Phosphoric acid and carbonic acid, as well as organic acids such as acetic acid, fumaric acid, malic acid, Citric acid, mandelic acid, tartaric acid and ascorbic acid. These salts with acids can according to the usual Process are produced. The examples illustrate the invention.

Example I.

2.9 g (6.3 nmol) of XK-62-2 and 9.4 g (69, ImMoI) sodium acetate trihydrate are dissolved in 145 ml of aqueous 50% dimethylformamide. 7.3 g (28.8 mmol) of / od are added to the solution, and the mixture is reacted for 15 hours with stirring at 55 ° C. The reaction mixture is then passed through a column filled with 150 ml of a cation exchange resin (H + form) The column is washed with 600 ml of water, then 2.0 N aqueous ammonia solution is applied, and about 250 ml of fractions which react positively with ninhydrin are collected and evaporated under reduced pressure to give 2.60 g of a readily yellowish residue. This residue is treated by column chromatography using 130 g of silica gel with a mixture of isopropanol, chloroform and concentrated aqueous ammonia solution in a ratio of 4: 1: 1. The elual is collected in fractions of 13 ml volume each No. 55 to 68 are combined and evaporated to dryness under reduced pressure to give 450 mg of unconverted XK-62-2. Fractions No. 75 to 83 become even if combined and evaporated to dryness under reduced pressure. 70 mg of 6'-N-Dcsmethyl-XK-62-2 (compound Mb.GcntamycinCu) are obtained.
M.p. 113 to 117 ^° C;

specific rotation [a] " + 171.1"
(c = 0.98, water).

IR spectrum (KBr, cm '):

3700 to 3000,2940,1630,1575, 1480, 1380,

1340, 1286,1146,1108,1052, 1021,957,820.
Nuclear Magnetic Resonance Spectrum (in D ₂ O) O (in ppm versus DSS):

1.20 (3H, s), 2.53 (3H, s),

5.13 (1H, d, J = 4.0 Hz), 5.23 (1H, d. J = 4.0 Hz)

₇ · H ₂ O:

Calc .: C 48.81, H 8.84, N 14.98;
Found: C 49.36, H 8.65, N 14.77.

Fractions No. 93 to 135 are concentrated under reduced pressure. Mün receives 1.38 g of 3 "-N-desmethyl-XK-62-2 (compound la).
M.p. 105 to 115 ° C;

specific rotation: ^]? + 148.5 °
(c = 0.097, water).
IR spectrum (K.Br, em- '):

3800 to 3000,2940,1640,1570,1465,

1379, 1330,1284, 1142, 1110,1050,1020,

955,865,810; see Fig. 1.
Nuclear Magnetic Resonance Spectrum (in methanol -di) f) (in ppm against TMS):

1.16 (3 H. s), 2.43 (3 H. s).

5.06 (1H, d, J = 3.9 Hz), 5.20 (1 H. d. | = 3.8 Hz);

see Fig. 2.

CwH) ₉ N ₁ O ₇ · H ₂ O:

Calc .: C 48.8 !, H 8.84, N 14.98;
Found: C 49.36, H 8.65, N 14.77.

Fractions No. 151 to 179 are evaporated to dryness under reduced pressure. 310 mg of 6'-N, 3 "-N-didesmethyl-XK-62-2 (compound Ib) are obtained.
F. 130 to 14O ⁰ C;

specific rotation: [α]? + 97.0 °
(c = 0.10. water).
IR spectrum (KBr.cm- '):

3700 to 3000.2950,1630,1570.1480.

1380, 1333, 1290, 1149, 1113, 1052, 1025, 958;

see Fig. 3.
Nuclear Magnetic Resonance Spectrum (in D ₂ O) O (ppm versus DSS):

1.18 (3H, s), 5.12 (1 H.d, | = 4.0 Hz).

5.29 (1H, d, J = 3.9 Hz); see Fig. 4th

C, ₈ H _i7 N, O ₇ · H ₂ O:

Calculated: C 47.67, H 8.67, N 15.44;
Found: C 47.54, H 8.39, N 15.23.

Example 2

463 mg (1.0MoI) XK-62-2 and 160 mg (4, OmMoI) Sodium hydroxide is dissolved in 25 ml of aqueous 50 percent dimethylacetamide. The solution is with 659 mg (2.0 mmol) potassium hexacyanofcrrate (III) were added. The mixture is reacted at 65 ° C. for 15 hours with stirring. Then the mixture is over one with 30 ml of a cation static har / .cs (H 'shape) given the loaded column. The column is then washed with 150 ml of water. Then 2.0 N aqueous ammonia solution is applied. Approximately 70 ml of fractions positive for ninhydrin react, willow obtained and evaporated under reduced pressure. 430 mg of one are easily obtained yellowish residue. This residue is column chromatographed using silica gel worked up according to example I. 98 mg of unset XK-62-2 are obtained. In addition, 20 mg is obtained Gentamycin Ci., (Compound II-b), 210 mg 3 "-N-Desmethyl-XK-62-2 (Compound I-a) and 55 mg of 6'-N.3 "-N-didesmethyl-XK-62-2 (Compound Ib).

Example 3

232 mg (0.5 mmol) of XK-62-2 are dissolved in 15 ml of water. The solution is mixed with 293 mg of fresh platinum tube, which has previously been activated with hydrogen. offset. The reaction then lasts 48 hours

ίο carried out long, the temperature being kept at 40 to 50 ⁰ C and a vigorous stream of fine air bubbles is bubbled through the reaction mixture. When the reaction has ended, the platinum black is filtered off and the filtrate is removed under reduced pressure

r, narrowed. 211 mg of residue are obtained. This The residue is worked up according to Example 1 by column chromatography using silica gel. 85 mg of unreacted XK-62-2 are obtained. 17 mg gentamycin Ci., (Compound II-b) are also obtained.

2u 82 mg of 3'-N-Desmethyl-XK-62-2 (Compound I-a) and 24 mg 6'-N, 3 "-N-didesmethyl-XK-62-2 (Compound Ib).

Example 4

r, 463 mg (1.0 mmol) of XK-62-2 are dissolved in 25 ml of water. The solution is 929 mg (5.9 mmol) Potassium permanganate added. The mixture is reacted for 17 hours at room temperature. Then will the reaction mixture over a column charged with 30 ml of a cation exchange resin (H ^ form) given. After washing the column with 120 ml of water, 2.0 N aqueous ammonia solution is broken up. About 80 ml of fractions that react positively with ninhydrin are collected and

evaporated under the current pressure. 426 mg of one are obtained slightly yellowish residue. This residue is column chromatographed using silica gel worked up according to example I. 110 mg of unreacted XK-62-2 are obtained. Furthermore, one obtains

■ to 15 mg gentamycin Ci., (Compound II-b), 135 mg 3 "-N-Desmethyl-XK-62-2 (Compound I-a) and 70 mg 6'-N.3" -N-Didcsmethyl-XK-62-2 (Compound I-b).

Example 5

4-, 449 mg (1, OmMoI) 3 "-N-Desmethyl-XK-62-2 (Compound l-a) and 2.04 g (15, OmMoI) sodium acetate trihydrate are in 30 ml of aqueous, 50 percent Dissolved dioxane. 2.04 g (8.0 mmol) of | od are added to the solution. The mixture is taking 14 hours

•, ο stirring at 60 ⁰ C implemented. The reaction mixture is then applied to a column charged with 30 ml of a cation exchange resin (II'-form). After washing the column with 150 ml of water, 2.0 N aqueous ammonia solution is applied. Approximately

γ, 50 ml of fractions which react positively with ninhydrin are collected and evaporated under reduced pressure. 420 mg of a slightly yellowish residue are obtained. This residue is .säulenchromatographisch using 20 g

With silica gel and a mixture of isopropanol, Chloroform and concentrated aqueous ammonia solution in a ratio of 4: 1: 1 as eluents treated. The eluate is removed in fractions of 13 ml volume. The parliamentary groups Nos. 37 to 49

h ^r > are combined and evaporated to dryness under reduced pressure. 50 mg of non-toxic 3 "-N-desmetliyl-XK-62-2 (compound Ia) are obtained. Fractions No. 61 to 76 are combined and added

evaporated to dryness under reduced pressure. 170 mg of 6'-N.3 "-N-didesmethyl-XK-62-2 (compound l-b).

Example 6

449 mg (1.OmMol) 3 "-N-Desmethyl-XK-62-2 (compound l-a) and 200 mg (5.0 mmol) sodium hydroxide are dissolved in 30 ml of aqueous, 50 percent Dimcthylacetamid. The solution is 824 mg (2.5 mmol) Potassium hexacyanoferrate (Oll) added. The mixture is reacted for 15 hours with stirring at 65 ° C. The reaction mixture is then poured over a 40 ml a quai ion exchange resin (H + form) charged Pillar given. After washing the column with 140 ml of water, it becomes 2.0 N aqueous ammonia solution upset. About 65 ml of ninhydrin positive fractions are collected and evaporated under reduced pressure. 410 mg of a slightly yellowish residue are obtained. This The residue is column chroniatographically using of silica gel according to Example 5 worked up. 220 mg of niehtumgesct / .tcs 3 "-N-Desmeihyl-XK-62-2 are obtained (Compound I-a). You also get 110 mg b'-N, 3 "-N-Didcsmelhyl-XK-62-2 (Compound I-b).

Example 7

225 mg (0.5 mmol) of 3 "-N-desmethyl-XK-62-2 (compound la) are dissolved in 20 ml of water. 400 mg of fresh platinum black, which has previously been activated with hydrogen, are then added to the solution the reaction is conducted for 45 Siunden long, the temperature being maintained at 50 to 60 ³ C and is bubbled a heavy stream of fine air bubbles through the reaction mixture. After completion of reaction, the platinum black is filtered and evaporated the Filtrai under reduced pressure. this gives 195 mg of residue. This residue is worked up by column chromatography using silica gel according to Example 5. 115 mg of unreacted 3 "-N-methyl-XK-62-2 (compound Ia) are obtained. In addition, 65 mg of 6'-N, 3 "-N-didesmethyl-XK-62-2 (compound Ib) are obtained.

Example 8

225 mg (0.5 mmol) of 3 "-N-Desmethyl-XK-62-2 (compound I-a) are dissolved in 110 ml of water. The 465 mg (3.0 mmol) of potassium permanganate are added to the solution. The mixture is 16 hours at Room temperature implemented. The reaction mixture is then poured over a 15 ml cation exchange resin (H * -form) given column loaded. After washing the column with 60 ml of water 2.0 N aqueous ammonia solution is applied. Approximately 40 ml of fractions positive for ninhydrin react, are recovered and evaporated under reduced pressure. 195 mg of one are easily obtained yellowish residue. This residue is column chromatographically worked up using silica gel according to Example 5. 87 mg of not converted 3 "-N-methyl-methyl-XK-62-2 (compound l-a). In addition, 63 mg of 6'-N, 3 "-N-didesmethyl-XK-62-2 (compound 1-b) are obtained.

Example 9

449 mg (1.0 mmol) 6'-N-Dcsmethyl-XK-62-2 (Gentamyein Ci,., Compound II-b) and 2.04 g (15, OmMoI) Sodium acetate trihydral is dissolved in 40 ml of aqueous 50% dimethylformamide. The solution 761 mg (3.0 mmol)] od are added. The mixture is reacted for 15 hours at 50 ° C. with stirring.

The reaction mixture is then poured over a 30 ml cation exchange resin (H + form) ι given column loaded. After washing the column with 130 ml of water, it becomes 2.0 N aqueous ammonia solution upset. About 60 ml ar fractions positive for ninhydrin are collected and evaporated under reduced pressure. You get

κι 430 mg of a slightly yellowish residue. This residue is column chromatographed using of 20 g of silica gel and a mixture of isopropyl alcohol, chloroform and concentrated aqueous Ammonia solution treated in a ratio of 4: 1: 1.

π The eluate is divided into fractions with a volume of 13 ml removed. The fractions No. 33 to 42 are combined and under reduced pressure to Evaporated to dryness. 89 mg of unreacted 6'-N-desmethyl-XK-62-2 (compound II-b) are obtained. the Fractions No. 63 to 85 are combined and evaporated to dryness under reduced pressure. Man receives 235 mg of 6'-N, 3 "-N-didesmethyl-XK-62-2 compound l-b).

_; _ Example I 10

449 mg (1.0 mmol) 6'-N-Desmeihyl-XK-62-2 (Genlamycin Ci ,,, compound II-b) and 160 mg (4.0 mmol) Sodium hydroxide is dissolved in 25 ml of aqueous 50 percent dimethylacetamide. The solution is with

ίο 659 mg (2, OmMoI) potassium hexacyanoferrate (lll) added. ^{The mixture is reacted at 60 °} C. for 15 hours with stirring. The reaction mixture is then passed through a column charged with 30 ml of a cation exchange resin (H + form). After this

π washing the column with 150 ml of water becomes 2.0-n given aqueous ammonia solution through the column. Approximately 80 ml of fractions positive for ninhydrin react, are combined and evaporated under reduced pressure. 415 mg of an easily obtained yellowish residue. This residue is column chromatically using silica gel according to Example 9 worked up. 115 mg of unreacted material are obtained 6'-N-Desmethyl! -XK-62-2 (Compound II-b). In addition, 275 mg of 6'-N, 3 "-N-Didcsmethyl-XK- are obtained

a; 62-2 (compound lb).

Example 11

225 mg (0.5 mmol) 6'-N-Desmethyl-XK-62-2 (Gentamycin Ci. ,, Compound II-b) in 20 ml of water

ίο solved. The solution is made with 400 mg of fresh platinum black added, which has previously been activated with hydrogen. Then the reaction is 50 hours carried out keeping the temperature at 40 to 50 ° C and a violent stream of fine

Y, air bubbles are bubbled into the reaction mixture. When the reaction has ended, the Plalinmohr is filtered off and the filtrate is evaporated under reduced pressure. 210 mg of residue are obtained. This residue is column chromatography under

The turn of silica gel according to Example 9 was worked up. 105 mg of unreacted 6'-NDcsmethyl-XK-62-2 (compound II-b) are obtained. 87 mg are also obtained 6'-N, 3 "-N-Didcsmethyl-XK-62-2 (Compound Ib).

Example 12

315 mg (0.75 mmol) 6'-N-Desmethyl-XK-62-2 (Genlamycin Ci ,,, compound II-b) are dissolved in 15 ml of water solved. The solution is with 465 mg (3.0 mmol)

Potassium precrnuinganal added. The mixture is reacted for 15 hours at room temperature. The reaction mixture is then passed through a column filled with 20 ml of a calcium ion exchange resin (H ⁴ form). After washing the column with 80 ml of water, 2.0 N aqueous ammonia solution is applied. About 45 ml of fractions which react positively with ninhydrin are combined and evaporated under reduced pressure. 290 mg of a slightly yellowish residue are obtained. This residue is worked up by column chromatography using silica gel as in Example 9. 85 mg of 6'-N-desmethyl-XK-62-2 (compound II-b) are obtained. 119 mg of 6'-N, 3 "-N-Didcsmethyl-XK-62-2 (compound Ib) are also obtained.

Example 13

454 mg (1, OmMoI) 6'-N, 3 "-N-didesmethyl-XK-62-2 (Compound l-b) are dissolved in 4 ml of water. The solution is cooled with a solution of 98 mg (1.0 mmol) of sulfuric acid in 1 ml of water. To Cold ethanol is added to the solution for 50 minutes until complete precipitation. The White The precipitate is filtered off. The monosullate of b'-N.3 "-N-Didesmetliyi XK-62-2 is obtained.

CkH ImN ₁ O ₁₁ S:

Calcd · C 40.52, H 7.37, N 13.13. S 6.00;
Found: C4L01, H 7.31, N 13.08, S 5.98.

Example 14

4.67 g (10, OmMoI) 3 "-N-Desmethyl-XK-62-2 (compound I-a) are dissolved in 20 ml of water. The solution 1.2 g (20% OmMoI) glacial acetic acid are added. After 30 Minutes, the solution is mixed with cold ethanol until complete precipitation. The white precipitate is filtered off. The diacetate of 3 "-N-desmethyl-XK-62-2 is obtained.

C ₂₁ H ₄₇ N ₅ O _n :

Calc .: C 48.49, H 8.32, N 12.29;
Found: C 48.56, H 8.35, N 12.27.

For this purpose 2 sheets of drawings

Claims (2)

Patent claims: 1. 3 "-N-monodesmethyl and 6'-N, 3" -N-didesmethyl derivatives of the antibiotic XK-62-2 of general formula I. NH ₂ \ NH, HO in which R denotes a methyl group or a hydrogen atom, and their salts with acids. 2. Process for the preparation of the compounds according to claim 1, characterized in that one a compound of the general formula II