DESCRIPTIONS OF ANTIBIOTICS 



351 



Mutants of S. racemochromogenus were then 

 isolated (4), and three substances, racemomycins 

 A, B, and C, were described. Racemomycin B is 

 synonymous with substance 229 B. Racemomycin 

 B has been most thoroughly investigated. The 

 relationship of the original 229 substance to race- 

 momycin A or C is not known. 



Method of extraction: Essentially like that of 

 streptomycin or streptothricin (3, 4). 



Chemical and physical properties: Original 229: 

 Basic substance. Colorless. Soluble in water. 

 Hydrochloride: m.p. 138-140°C. Sulfate: m.p. 198- 

 200°C (decomposition). /^emecA-o/e.- m.p. 169-171 °C 

 (decomposition). Helianthate: m.p. 234-239°C (de- 

 composition). Positive Molisch and Elson-Morgan 

 tests. Negative Sakaguchi, maltol, Fehling, 

 FeClii , biuret, and ninhydrin tests. Most stable to 

 boiling at pH 5.0; moderately stable at pH 2.0; 

 least stable at pH 9.0. Racemomycin B (229B): 

 Basic substance, containing strong and weak basic 

 groups. Free Base: White hygroscopic powder; 

 m.p. 150°C (decomposition). Infrared spectrum 

 given in reference 4. [a]o = —34° (c = 0.5 per cent 

 in water). Positive Molisch, Elson-Morgan, biuret, 

 and ninhydrin tests. Negative Sakaguchi, maltol, 

 FeCls , 2,4-dinitrophenylhydrazine, and Fehling 

 tests. Gives a white precipitate with both HgCla 

 and phosphotungstic acid (4). Data on paper 

 chromatography given in references 3 and 4. 

 C6oHi.,s032N.>o :" C = 41.53%; H = 8.29%; N = 

 16.51% (4, 6). Hydrolysis products include /3-ly- 

 sine, streptolidine (geamine, roseonine) (5), and a 

 reducing sugar (4). Racemomycin B is considered 

 to differ from geomycin and roseothricin because 

 the ratios of the amounts formed of these products 

 from one mole of each antibiotic differ (6). Hydro- 

 chloride: White hygroscopic powder; m.p. 175 °C 

 (decomposition), [a]^, = —45° (c = 0.5 per cent 

 in water). Sulfate: White hygroscopic powder; 

 m.p. 203°C (decomposition). Helianthate: Dark 

 red, amorphous powder; m.p. 210°C (decomposi- 

 tion). p-{p-Hydroxyphenylazo)henzene sulfonate: 

 Orange-yellow amorphous substance; m.p. 207°C. 

 Picrate: Yellow hygroscopic powder; m.p. 198°C. 

 Titration data given in reference 4. Reineckate: 

 Purple (4); m.p. 172-175°C (decomposition) (3). 

 \' -Benzoyl derivative: m.p. 209°C (decomposition) 

 (4). Racemomycin C: Closely related to racemomy- 

 cin B. Isolated as the p-(io-hydroxyphenylazo)ben- 

 zene sulfonate salt; m.p. 210°C (decomposition). 

 C15H32O8N., (4). 



Biological activity: Original 229: Active on 

 gram-positive and gram-negative bacteria. Cross- 

 resistance with streptothricin but not strepto- 

 mycin. Diffuses faster in agar than 229B or strep- 



tomycin (3). Racemomycin B: Activity resembles 

 229, but is less active on mycobacteria (3). 



Toxicity: Original 229 (crude): LDso (mice) 216 

 Mg per kg (no route given). No delayed toxicity 

 (3). Racemomycin B (crude). LDso (mice) 62.3 mg 

 per kg (intravenously). Has considerable delayed 

 toxicity. 



References: 



1. Otani, S. and Sugai, T. J. Antil)iotics 



(Japan) 6B: 257, 1953. 



2. Otani, S. and Svigai, T. J. Antibiotics 



(Japan) 6B: 372-373, 1953. 



3. Sugai, T. J. Antibiotics (Japan) 9B: 170- 



179, 1956. 



4. Taniyama, H. and Takemura, S. J. Pharm. 



Soc. Japan 77: 1210-1214, 1957. 



5. Taniyama, H. and Takemura, S. J. Pharni. 



Soc. Japan 77: 1215-1217, 1957. 



6. Taniyama, H. and Takemura, S. Yakugaku 



Zasshi 7«: 742-744, 1958. 



Hue lino 111 veins 



Produced l)y: Strcptoinyces sp. closely related to 

 <S. phacochromogenes (1, 3). 



Method of extraction: I. Broth-filtrate ex- 

 tractctl with butyl acetate. Extract concentrated 

 in vacuo and chromatographed on alumina. De- 

 veloped with ethyl acetate. Eluate concentrated 

 and cooled, giving crude ractinomycin. Crystals 

 extracted with ether; ether concentrated and 

 cooled to give ractinomy<in A. Ether-insolul)le 

 residue taken up in ethyl acetate, then cooled to 

 give ractinomycin B (1). II. Broth adjusted to 

 pH5.0 and filtered. Antibiotic adsorbed on active 

 clay, and eluted with acetone. Antibiotic precipi- 

 tates when the extract is concentrated in vacuo. 

 Precipitate and liquor extracted with ethyl ace- 

 tate. Extract concentrated in vacuo and cooled to 

 give orange crystals of ractinomycin A. Recrystal- 

 lization from ether. Mycelium extracted with 

 acetone (3). 



Chemical and physical properties: Ractinomycin 

 A: Orange needles. Turns brown at 157-158°C and 

 blackens at 205°C. Most soluble in chloroform and 

 acetone; soluble in ethyl and butyl acetates; 

 slightly soluble in methanol, ethanol, benzene, 

 and carbon disulfide; almost insoluble in petro- 

 leum ether and water. \^i^^ 245 m^ (^IL 780) 440 

 to 450 m/i (E\7m 220). Infrared spectrum given in ref- 

 erence 3. Positive Tollen, FeCl.^, and Molisch tests. 

 Decolorizes KMn04 . A sodium carbonate solution 

 of A is decolorized by HjOs • In aqueous solution, 

 turns from yellow to jjurple at pH 6.4 to 6.6; 

 above this pH it is not stable. In concentrated 

 H-2S04 , tui'ns from reddish violet to l)lue; in con- 



