DE1035146B - Process for the preparation of chloractinomycins - Google Patents

Description

Process for making chloractinomycins The actinomycins are chromopeptides whose chromophoric group according to Brockmann and co-workers (Angewandte Chemie, Vol. 68, 1956 pp. 70, 71) the 3-amino-1,8-dimethylphenoxazon- (2) -4,5-dicarboxylic acid (also called >> Actinocina, see p. 69). The actinomvcine under the conditions described in German patent 954 251 in desaminoactinomycine be transferred, which differ from the actinomycins in that the 3-position amino group is replaced by an oxy group. These desaminoactinomycins no longer have the inhibitory effect against microorganisms, the actinomycins is own.

It has now been found that new derivatives of actinomycin can be obtained can come when one has the 3-position on the phenoxazone skeleton of the desaminoactinomycins located hydroxyl group replaced by a chlorine atom. It's surprising that the action of thionyl chloride required for this does not affect the rest of the molecule destroyed, in particular that the side chains closed to form lactone rings implementation are unchanged. With ammonia deliver those which can be produced by the process Compounds the corresponding Actinomy cine (see. Patent application F 20374 IVb / 12p).

The conversion of the hydroxyl group in the 3-position on the phenoxazone skeleton the desaminoactinomycins are made by treatment with thionyl chloride. An addition of auxiliaries that facilitate chlorination, such as chloranil, is recommended.

The desaminoactinomycins used as starting materials are chromopeptides, the metabolic products of the corresponding metabolites called actinomycins the actinomycotes by exchanging an amino group on the phenoxazone structure for a Derive hydroxyl group. One can start from the pure connections like them represent the desaminoactinomycins Cl, C, C, 10, h, X1 and X2. Likewise you can also mixtures, e.g. B. the desaminoactinomycins C, J or F, use.

The new compounds are antibacterial and are intended to Serving manufacture of remedies. They can also be used to Actinomycins which have become ineffective through hydrolysis of the amino group are converted back into effective ones Transfer connections.

EXAMPLE A solution of 250 mg of desaminoactinomycin and 70 mg of chloranil in 50 cc of benzene is heated to boiling with 5 cc of thionyl chloride for 20 minutes. After the solvent has evaporated off in vacuo, the residue is dissolved in benzene, the solution is passed through a column of aluminum oxide (Brockmann, activity level II) and this is washed with plenty of benzene. The chloractinomycin C remaining as a red zone in the column is washed out with benzene containing 25% ethyl acetate. When these solvents evaporate, an amorphous red mass is left behind, which is deposited in red, trapezoidal crystals when it is dissolved from ethyl acetate. The chloractinomycin obtained has a specific ultraviolet absorption curve (see Fig. 1) and infrared absorption curve (see Fig. 2) and a specific R, value in two different solvent mixtures, its specific rotation is [a] 'D' = -131 ° 1L15 ° (c = 0.10 in acetone). The yield is 70 % of theory.

Analysis of Chloractinomycin C Found ................. Cl 2.5%, N 11.19%; calculated ................ C12.750 / 0, N 11.7%. The R value is the ratio of R - running distance of the running distance of the corresponding Actinomycinderivates actinomycin R, the Chloractinomycins C a) inButanol-n-dibutyl-10 ° / oigeswäßriges sodium m- kresotinat (1: 1: 2) ... ... = 1.72; b) in butyl acetate n-dibutyl ether 10% aqueous sodium m-cresotinate (3: 1: 2) .. = 0.83.

Claims (1)

PATENT CLAIM: Process for the production of chloractinomycins, characterized in that one desaminoactinomycins with thionyl chloride in the heat treated.