DE2550168C3 - 3 "-N-monodesmethyl and 6'-N, 3" -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

in which R is a methyl group or a hydrogen atom means and their salts with acids.

2. Process for making the compounds

OH

according to claim 1, characterized in that a compound of the general formula II

(H)

in which either R ¹ and R ² each represent methyl groups (antibiotic XKL-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 reacts 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 DE-PS 23 26 781 described.

3 4

The process according to the invention can be represented by the following reaction shear:

Compound Il-a (XK-62-2)

reaction

NH ₂ \ NH ₂ O

HO

Compound I-a (3 "-N-Desmethyl XK-62-2)

_H0 J / NH _;

OH

Reakiic-. Il

Compound II-b (6-N-Desmethyl-XK-62-2. Gentamy in C ₁ ,,)

Reaction III

Connection l-b

(6-N, 3 "-N-Didesmelh> l

XK-62-2)

NH ₂

OH

The invention is explained in more detail below 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 l-a and l-b are new, valuable ones Antibiotics.

The connection l-a. 3'-N-Desmethyl-XK-b2-2 has an antibiotic effect comparable to that of XK-62-2. however, a lower toxicity.

The compound ll-b isi as gentamycin Ci., From animal US-PS 30 9I 572 known.

If the connections l-a or lib with a Oxidizing agents of the type mentioned in claim 2 are reacted, so the 6'-N or 3 "-N-methyl groups the respective compound is eliminated to form the compound l-b.

The connection l-b. b'-N.3 "-N-Didesmetli \ l-Xkb2-2 is also comparable to XK-62-2 in its anlibiotic effect and also has a lower level Toxicity than this known antibiotic.

To remove the methylation of compound II-a Compounds I-a and II-b preferentially the reaction I. because the 3 "-N-Mcihvlgruppe easier than that b-N-Methvlgruppe is eliminated. Therefore become the Preparation of the compound l-a preferably mild reaction conditions used while for the preparation the compound II-b comparatively energetic reaction conditions are applied.

It should also be noted that in a case according to the invention ["ntmethylation of the compound II-a a further F.iiimethylation of the compounds I-a and II-b is inevitable. A reaction mixture is thus obtained which generally contains the compounds l-a. ll-b and l-b contains, although the quantitative ratio of the individual compounds to one another depending on the Reaction conditions varied. As already mentioned, the yield of compound I-a is under mild reaction conditions relatively high, while the yield under comparatively strict reaction conditions at connection II-b increases. Eventually, under very severe reaction conditions, the yield will decrease Connection l-b high and that at connection II-b very low.

For the preparation of the compound l-b from the compound l-a after the reaction IM are used preferably relatively energetic 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, iodine is used as the oxidizing agent. Potassium hexacyanoferrate (III). Air or potassium permanganate are used. In general, 0.5 to 15.0 moles of oxidizing agent are used used per 1 mole of starting compound. When using air, the oxidizing agent becomes in For small bubbles through the reaction medium pearled.

As a solvent for carrying out the invention Reaction solvents can be used in which the reactants and which do not react or react only to a very limited extent with the participants in the reaction. For example can be water or mixtures of water with methanol. Ethanol. Tetrahydrofuran. Dimethylacetamide. Dimethylformamide. Dioxane and ethylene glycol dimethyl ether can be used.

The starting compounds are dissolved in the solvent in a concentration of 4.5 to 50 millimolar.

The reaction according to the invention is, depending on the type of oxidizing agent used, at a pH of 4 to 12 carried out. Adjusting the pH can be achieved by adding an appropriate acid or base. There are such acids or bases too use that neither decompose the starting compounds nor the dcmelhylated products 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 inorganic acids are (hydrochloric acid and sulfur l'elsä nc. Examples of corresponding organic acids include acetic acid and formic acid. Hot examples fin corresponding bases are alkali metal hydroxides. Erdal kai! Metal hydroxide. Alkali metal carbonates. Alkaline earth metal carbonates. Alkali.ueliillalkoxides and alkali and Alkaline earth metal salts of carboxylic acids.

The setting of the pH value can be either \ < > i Reaklionsbeginn oiler can be carried out during the reaction.

The reaction according to the invention is carried out at temperatures from --20 to 100 C. sometimes 0 to 70 ( w ähreiu! 30 minutes to 50 hours.

The reaction conditions to be used in practice are sii depending on the type of product desired and the oxidizing agent used chosen so that the highest possible yields are achieved and undesired reactions of other functional groups, like the hydroxyl and amino groups of the starting compounds. be avoided.

For example, when using | od. the preferred oxidizing agent for reaction I. the following reaction conditions are preferred: 0.7 to IOX Preferably 2.0 to 0 moles of iodine per 1 mole of XK-62-2: reaction temperatures from -10 to 90.degree preferably 40 to 60 C: and reaction times of 1 to 24 hours, preferably 2 to 15 hours. Fernei 0.5 to 6.0 mol, preferably 2.0 to 4.0 mol of a strong base or 5.C. are used to adjust the pH up to 25.0 mol: preferably 7.0 to 15 mol of a weak base added.

To carry out reactions II. III and IV and for the preparation of the compound l-b from the compound 11-ii, the following reaction conditions are preferred

1 to 13 mol. Preferably 5 to 9 mol: 2 to 15 mol preferably b to 11 moles: 0.7 to 10 moles, preferably

2 to 6 mol: or 3 to 15 mol. Preferably 7 to 11 mol ) od per 1 mole of the starting compounds. The other reaction conditions are the same as for dei Reaction I.

After the reaction has ended, the products are obtained in the usual way. For example, there is; The reaction mixture is neutralized and concentrated under reduced pressure. The concentrate is put on a mi a cation exchange resin charged column set on which the unreacted starting compound fertilize and the reaction products are adsorbed The column is washed with water and then c eluted with 2.0-N aqueous ammonia solution. The Elua is concentrated and the products are isolated and purified in the usual way, for example by means of Column chromatography and thin layer chromatography using ion exchange resins Pebbles. Alumina and cellulose.

In table I are the values for the acute toxi / iliil (I.Diii) of the compounds Ha, la. lib and Ib for mice specified.

Table I.

Connection Ma
Connection la

Ι.Ο, ο mg / kg (iv)

200

Compound I Ib Compound l-b

ID, »mg / kg (iv)

88
138

Table II shows the antibacterial spectrum of the Compounds II-a, l-a. ll-b and l-b against different Granipositive and grain-negative bacteria are indicated. The minimum inhibitory concentrations are by dilution to double the volume at pH 8.0 certainly.

labile Il

Dumb ones

Minimal llcmmkon / cnlratinn (MIIK / μ / ml)

Verb, ll-a \ erb. L-a Vorh. ll-h \ erh. l-li

l'seudonionas aeruuinosa
IiMII I 1.04 2.08 0.52 0.26 Staphylococcus au re us
Λ ICC 6538 I ' 0.008 0.0 K. <0.004 <0.004 Bacillus suhtilis
No. 10707 <0.004 0.008 <0.004 <0.004 I'rotcus vulgaris
ATCC 6897 0.0 () 5 0.13 0.033 0.033 Shigella sonnci
ATCC 92 ^', 1O 0.13 0.13 0.0 (0 0.065 Salmonella tvphosa
ATCC 9992 0.033 0.065 0.016 0.033 Klebsiella pncunioniuc
ATCC 10031 0.016 0.033 0.008 <0.004 I'scherichiu coli
ATCC 2 (i 0.065 0.13 0.033 0.016 Hscherichia coli
KY 8327 8.34 2.08 4.17 4.17 Escherichia coli
KY 8348 1.04 2.08 1.04 1.04

The microorganisms Kseherichia coli KY 8327 and KY 8348 listed in Table II form intracellular adenoid transferase or acetyl transferase. The former bacterial strain inactivates kanamycins and cjentamvcine by adenylation. while the latter inactivates genamycins by acetylation.

Those produced by the method according to 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 be prepared by conventional methods. Explain the examples The invention.

example 1

2.9g (6.3 mMo!) XK-62-2 and 9.4 g (69, ImMoI) Sodium acetate trihydrate in 145 ml of aqueous. Dissolved 50 percent dimethylformamide. The solution 7.3 g (28.8 mmol) of iodine are added, and that The mixture is stirred at 55 ° C. for 15 hours

4Ί implemented. Then the reaction mixture passed through a column charged with 150 ml of a cation exchange resin (H form). The pillar will washed with b00 ml of water. Then 2.0 N aqueous ammonia solution is applied. About 250 ml

ίο from fractions that react positively with ninhydrin, are recovered and evaporated under reduced pressure. 2.60 g of a slightly yellowish one are obtained Residue. This residue is column chromatography using 130 g of silica gel with a Mixture of isopropanol, chloroform and concentrated aqueous ammonia solution in the ratio of 4: 1: 1 treated as eluent. The eluate is collected in fractions of 13 ml each. the Fractions No. 55 to 68 who united and under

bo evaporated to dryness under reduced pressure. 450 mg of unreacted XK-62-2 are obtained. Fractions No. 75 to 83 are also combined and evaporated to dryness under reduced pressure. 70 mg of 6'-N-desmethyl-XK-62-2 (compound II-b.GentamycinCi.,) Are obtained.
F. U3bisl17 ^c C;
specific rotation ^]? + 171.1
(C = 0.98. Water).

IR spectrum (KHr.ein '):

3700 to JOOO. 2940. IbiO. 1575, 1480, 1380.

1340. 128b. 1146.1108, 1052, 1021,957.820. NMR spectrum (in D) O) Λ (in ppm against DSS):

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

5.13 (1 H, i.e. J = 4.0 Hz), 5.23 (I H.il. 1 = 4.0 H /)

CH _n N ₁ O, · H, O:

Calc .: C 48.81 H 8.84, N 14.98;

Found: C 49.3b. 118.65. N 14.77. κι

The parliamentary groups No. 93 to 135 are under concentrated under reduced pressure. 1.38 g is obtained 3 "-N-Dcsmethvl-XK-62-2 (Compound I-a). M.p. 105 to I 15 C; 1""

specific rotation: [\]? + 148.5
(c = 0.097. water).
IR spectrum (KBr.cm '):

3800 to 3000.2940, 1640, 1570. 1465,

137 ')! 33O! 284'.! '! 2 !!! 0! 050! 020 ¹ U

955,865,810; see Γ ig. 1.
NMR spectrum (in methanol -di) <) (in ppm against TMS):

1.16 (3 II. S). 2.43 (3 sts ).

5.06 (1 H. el. | = 3.9 Hz), 5.20 (1 II.d, J = 3.8 I Iz): see Fig. 2.

CwH ₁₁₁ N ₅ O ₇ ■ H ₂ O:

Ber: C 48.81. H 8.84, N 14.98;

Found: C 49.36, H 8.65, N 14.77. _{l (l}

Fractions No. 151 to 179 are evaporated to dryness under reduced pressure. This gives 310 mg of 6'-N, 3 "-N-didesmethyl-XK-62-2 (Compound lb) j-, F. 130 to 14O ⁰ C.

specific rotation: [ix] "+ 97.0 °
(C = O ₁ IO, 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) O) .5 (ppm versus DSS):

1.18 (3 H. s). 5.12 (Ί H, d, J = 4.0 Hz).

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

C ₁₈ Hj ₇ N ₅ O ₇ · H ₂ O:

Calc .: 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 50 percent aqueous Dissolved dimethylacetamide. The solution is mixed with 659 mg (2, OmMoI) potassium hexacyanoferrate (III). The mixture is reacted at 65 ° C. for 15 hours with stirring. Then the mixture is over given a column charged with 30 ml of a cation exchange resin (H * form). Afterward the column is washed with 150 ml of water. Then b0 2.0 N aqueous ammonia solution is applied. Approximately 70 ml of fractions positive for ninhydrin react, are recovered and evaporated under reduced pressure. 430 mg of one are easily obtained yellowish residue. This residue is column chromatographed using Kieelgel worked up according to example 1. 98 mg of unreacted XK-62-2 are obtained. In addition, 20 mg is obtained Gintamyein Ci ,, (Compound II-b), 210 mg 3 "-N-Desmylhyl-XK-62-2 (Compound I-a) and 55 mg of 6'-N.3 "-N-Didcsmethyl-Xli.-62-2 (Compound l-b).

Example 3

232 mg (0.5 mol) of XK-62-2 are dissolved in 15 ml of water. The solution is made with 293 mg of fresh platinum tube. which has previously been activated with hydrogen. offset. Subsequently, the reaction is carried out for 48 hours while the temperature is maintained at 40 to 50 ⁰ C and a heavy stream is bubbled of fine air bubbles by the Reakiionsgemisch. When the reaction has ended, the Plalinmohr is filtered off and the filtrate is concentrated under reduced pressure. 211 mg of residue are obtained. This residue is säiilenchminatogniphisch using Kicselgel according to Example 1. 85 mg of unreacted XK-b2-2 are obtained. 17 mg of cientamycin Ci ,, (compound II-b) are also obtained. «2 mg 3'-N-Pesm <Mhyl-XK-h? -? (Compound Ia) and 24 mg of 6'-N.3 "-N-Didesmelhyl-XK-b2-2 (Compound Ib).

Example 4

4bi mg (1.0 niMol) of XK-62-2 are dissolved in 25 ml of water solved. 929 mg (5.9 mmol) of potassium permanganate are added to the solution. The mixture turns 17 Reacted hours at room temperature. The reaction mixture is then over a 30 ml Quai ion exchange resin (I I 'form) is given to the charged column. After washing the column with 120 ml 2.0 N aqueous ammonia solution is applied to water. About 80 ml of fractions obtained with ninhydrin react positively, are recovered and evaporated under reduced pressure. 426 mg of one are obtained slightly yellowish residue. This residue is column chromatographed using silica gel worked up according to example 1. 110 mg of unreacted XK-62-2 are obtained. Furthermore, one obtains 15 mg gentamycin Ci ,, (compound II-b), 135 mg 3 "-N-desmethyl-XK-62-2 (compound la) and 70 mg b'-N.3 "-N-didesmethyl-XK-62-2 (Compound I-b).

Example 5

449 mg (1, OmMoI) 3 "-N-Desmeihyl-XK-62-2 (compound Ia) and 2.04 g (15.0 mmol) sodium acetate trihydrate are dissolved in 30 ml aqueous, 50 percent dioxane. The solution is od added the mixture is reacted for 14 hours under stirring at 6O ⁰ C. then the reaction mixture is to a 30 ml of a cation exchange resin (H ⁺ form) packed column by | with 2.04 g (8.0 mmol)... After washing the column with 150 ml of water, 2.0 N aqueous ammonia solution is applied. About 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 treated by column chromatography using 20 g of silica gel and a mixture of isopropanol, chloroform and concentrated aqueous ammonia solution in a ratio of 4: 1: 1. The eluate is removed in fractions of 13 ml volume. Fractions 37 to 49 are combined and evaporated to dryness under reduced pressure. 150 mg of unreacted 3 "-N-Desmethyi-XK-62-2 (compound Ia) are obtained. Fractions No. 61 to 76 are combined and taken under

Il

\ ci mirulertem pressure / evaporated to dryness. Man received 170 mg (V-N.3 "-N-Didcsmethyl-XK-62-2 (compound l-b).

B e i s ρ i e I b

449mg (1, OmMoI) 3 "-N-Desmcthy! -XK-62-2 (Compound I-a) and 200 mg (5.OmMoI) sodium hydroxide are in 30 ml of aqueous. 50% dimethylacetamide dissolved. The solution is 824 mg (2.5 niMoi) Potassium hydrogen cyanoferrate (III) added. The mixture κι is 15 hours with stirring at 65 C umgcsel / t. The reaction mixture is then via a 40 ml a Kalionenaiistauscherhaives (11 x form) charged Pillar given. After washing the column with 140 ml of water, 2.0 N aqueous ammonia solution is obtained. applied, about 65 ml of fractions positive for ninhydrin are collected and evaporated under reduced pressure. 410 mg of a slightly yellowish residue are obtained. This Kiicksiand is siiiilenrliromatographisch under Ver Jn Turn of silica gel according to example ~> worked up. You get . 30 mg nichtiimgesel / les 3 "-N-i) esmeih \ l-XK-62-2 (Compound la), one also obtains ll () m; j 6'-N. S "-N-Didesmeth> I-X K-62-2 (Compound I-b).

Example/

225 mg (0.5 nmol) of 3 "-N-Desmethyl-XK-b2-2 (compound la) are dissolved in 20 ml of water. 400 mg of fresh platinum black, which has previously been activated with hydrogen, are added to the solution. Then j _n, the reaction is conducted for 45 hours while the temperature is maintained at 50 to 60 C and a heavy stream of fine air bubbles is bubbled through the reaction mixture. After completion of reaction, the platinum black is filtered off and the filtrate was evaporated under j-, reduced pressure. 195 mg of residue are obtained. This residue is worked up by column chromatography using silica gel according to Example 5. 115 mg of non-condensed 3 "-N-methylhyl-XK-62-2 (compound Ia) are obtained. Furthermore , 65 mg of 6N.3 "-N-didesemethyl-XK-62-2 (compound Ib) are obtained.

Example 8

225 mg (0.5 mmol) of 3 "-N-desmethyl-XK-b2-2 (compound _A -, compound la) are dissolved in 110 ml of water. The solution is mixed with 465 mg (3.0 mmol) of potassium peranganate. The mixture is reacted for 16 hours at room temperature. The reaction mixture is then passed through a column charged with 15 ml of a cation exchange resin (H 'form). After washing the column with 60 ml of water, 2.0 N aqueous ammonia solution is obtained About 40 ml of fractions which react positively with ninhydrin are collected and evaporated under reduced pressure. 195 mg of a slightly yellowish residue are obtained. This residue is worked up by column chromatography using silica gel according to Example 5. 87 mg of unreacted 3 are obtained "-N-desmethyl-XK-62-2 _(b0 connects dung Ia). In addition, 63 mg of 6'-N, 3 "-N-didesmethyl-XK-62-2 (compound Ib) are obtained.

Example 9

449 mg (1.0 mmol) 6'-N-Desmethyl-XK-62-2 (Gentamycin Cij, compound II-b) and 2.04 g (15, OmMoI) Sodium acetate lrihydrai are in 40 ml of aqueous Dissolved 50 percent dimethylformamide. 761 mg (3, OmMoI) iodine are added to the solution. The mixture is reacted at 50 C for 15 hours with stirring.

The reaction mixture is then poured over a 30 ml cation exchange resin (H 'form) given column loaded. After washing the Column with 130 ml of water becomes 2.0 N aqueous ammonia solution upset. About 60 ml of ninhydrin positive fractions are collected and evaporated under reduced pressure. 430 mg of a slightly yellowish residue are obtained. This The residue is column chromatographed using 20 g of silica gel and a mixture of Isopropanol. Treated chloroform and concentrated aqueous ammonia solution in a ratio of 4: 1: 1. The F.luat is divided into fractions with a volume of 13 ril removed. The parliamentary groups No. 33 to 42 are combined and evaporated to dryness under reduced pressure. 89 mg of non-reversible chemicals are obtained (V-N-Desmethvl-XK-b2-2 (Compound II-b). The l'ractions No. 6 3 to 83 pasture united uix! linier evaporated to dryness under reduced pressure. 293 mg of b'-N.i "-N-didesmeth \ l -. \ K-62-2 compound are obtained l-b).

Example 10

449 mg (1.0 mmol) b-N -IX-smeilul-XK-62-2 (Gentanncin Ci.,. Compound II-b) and 160 mg (4.OmMoI) sodium hydroxide are in 25 ml aqueous. 50 percent Dissolved dimethylacetamide. 39 mg (2.0 mmol) of potassium hexacvanoferrate (III) are added to the solution. The mixture is reacted at 60 ° C. for 15 hours with stirring. Then the reaction mixture passed through a column charged with 30 ml of a cation exchanger haiv.es (H · form). After this Washing the column with 150 ml of water, 2.0 N aqueous ammonia solution is passed over the column. About 80 ml of fractions that react positively with ninhydrin are pooled and reduced under reduced pressure Pressure evaporated. 415 mg of a slightly yellowish residue are obtained. This residue becomes very automatic worked up using pebble urchins according to Example 9. 115 mg of unreacted material are obtained 6-N "Desmethyl-XK-b2-2 (compound II-b). In addition, 275 mg of b'-N.3 '-N-didesmethyl-XK-b2-2 (compound l-b).

Example Il

225 mg (0.5 mmol) b'-N-Desmeih \ l-XK-62-2 (Gentannein Ci ... compound ll-b) are dissolved in 20ml of water solved. 400 mg of fresh platinum black, which had previously been activated with hydrogen, are added to the solution is. Then the reaction is 50 hours carried out, keeping the temperature at 40 to 50 C and a violent stream of fine Air bubbles are bubbled into the reaction mixture. When the conversion is complete, the platinum black becomes filtered off and the filtrate evaporated under reduced pressure. 210 mg of residue are obtained. This The residue is worked up according to Example 9 by column chromatography using silica gel. 105 mg of unreacted 6'-N-desmeth \ l-XK-62-2 (compound I Ib) are obtained. 87 mg are also obtained b'-N.3 "-N-Didesmethyi-XK-62-2 (Compound I-b).

Example 12

315 mg (0.75 mmol) 6'-N-Desmethyl-XK-62-2 (Gentamycin Cu. Compound Mb) are in! 5 ml of water solved. The solution is with 465 mg (3.0 mmol)

Kaliunipermanganai versetz !. The mixture is reacted for 15 hours at room temperature. The reaction mixture is then passed through a column charged with 20 ml of a calcium ion exchange resin (H ^T 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 according to Example 9 by column chromatography using silica gel. 85 mg of 6'-N-desmethyl-XK-62-2 (compound II-b) are obtained. 119 mg of 6'-N, 3 "-N-didesmethyI-XK-62-2 (compound Ib) are also obtained.

Example 13

454 mg (1, OmMoI) b'-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 were added. To

JO minutes the solution will be complete! Cold ethanol is added to the precipitate. The white precipitate is filtered off. The monosul is obtained fat from b'-N.3 "-N-didesmeth \! - XK-t> 2-2.

Calc .: C 40.52, H 7.37, N 13.13, S 6.00:
found: C 41.01, H 7.31. N 13.08, S 5.98.

Example 14

4.67 g (10.0 mmol) 3 "-N-Desmethyl-XK-62-2 (Ver bond l-a) are dissolved in 20 ml of water. The solution 1.2 g (20% OmMoI) glacial acetic acid are added. After 3 ( The solution takes minutes to complete precipitation is mixed with cold ethanol. The white sleep is filtered off. The diacetate of 3 "-N-Des methyl-XK-62-2 is obtained.

Bcr .: C 48.49, H 832, N 12.29;
Found: C 48.56. H 8.35, N 12.27.

For this purpose 2 sheets of drawings

Claims (1)

Claims; 1,3 "-N-monodesmethyl and 6'-N, 3" -N-didesmethyl derivatives of the antibiotic XK-62-2 of general formula I. NHA NH-, O HO