DESCRIPTIONS OF ANTIBIOTICS 



359 



Eberthella typhosa infections in mice (4, 8). Also 

 active on Sal. typhi, V. cholerae, and PasleiireUa 

 lularensis infections in mice (10) . Increases growth 

 of chickens when added to the diet (4). 



Toxicity: Mice tolerate about 1 gm per kg (HCl 

 .salt) intravenously and sul)cut;ineously (1). 



References: 



1. Kikuchi, M. J. Antibiotics (Japan) :i: 839- 



844, 1950. 



2. Ishida, N. J. Antil)iotics (Jai)an) 3: 845- 



853, 1950. 



3. Nagao, I. J. Antil)iotics (Japan) 3(8uppl. 



C): 20-23, 1950. 



4. Nagao, I. J. Antil)iotics (Japan) 4: 24- 



28, 1951. 



5. Ishida, N. Tohoku J. Kxptl. Med. 54: 



180, 1951. 



6. Kuroya, M. et ul. Tohoku J. Ivxptl. Med. 



53: 209-217, 1952. 



7. Kuroya, M. et al. Tohoku J. Exptl. Med. 



55: 289-297, 1952. 



8. Aliyamori, A. J. Antibiotics (Japan) 5: 



163 165, 1952. 



9. Takahashi, T. et al. J. Antil)iotics (Japan) 



6B: 452-454, 1953. 

 10. Ishida, N. Tohoku J. Exptl. Med. 58: 

 153-161, 1953. 



Ro.seothriciii 



Produced by: Streptomyces roseochromogenes (9). 



Remarks: Streptothricin-like substance. Roseo- 

 thricin A may be identical to streptothricin VI 

 and to part of the mycothricin complex (14) (.see 

 streptothricin-like antibiotics) . 



Synonyms: Antibiotic H 277 (1, 8). Antibiotic 



chloride. Purification by chromatography on 

 alumina from methanol. Developed with metha- 

 nol, 80 per cent methanol and water. Concentrated 

 active fractions freeze dried. Converted to helian- 

 thate (1). Paper chromatography (butanol-metha- 

 nol-water containing 3 per cent ammonium reinec- 

 kate, 4:1:2) indicates a nvmiber of components, 

 with Rf values of 0.04, 0.16, 0.33, 0.54, and 0.77 

 (3, 5). Component A can be separated from B and 

 C by chromatography on Amberlite IRC-50 (Na"*" 

 phase) at pH 7.0 (7) and developed with citric 

 acid-HCl buffer, starting with pH 4.6 and with 

 gradual lowering of the pH by 0.2 unit (9) or with 

 2 per cent ammonium sulfate solution. Compo- 

 nent A can be precipitated as the phosjjhot ung- 

 state (13). 



Chemical and physical properties: Basic sub- 

 stance. Complex: Helianthate: m.p. 215-218°C. 

 Reineckate: m.p. 185-190°C. Picrolonate: m.p. 

 225-230°C (decomposition). C = 48.23%; H = 

 5.63%; N = 20.34%. Positive Elson-Morgan, nin- 

 hydrin, biuret, and Fehling tests. Negative 

 Tollen, Pauly, Bial, Nylander, Millon, Trommers, 

 Molisch, Folin, Hopkins-Cole, Sakaguchi, and 

 maltol tests. Inactivated by KMn04 , formalin, 

 and 1.0 A^ methanolic HCl. Partially inactivated 

 by cysteine. Not inactivated by H2O1 or hydrox- 

 ylamine (1,9). Component A: Molecular weight, 

 about 900. pK values of 11.4, 10.6, 9.6, 9.0, 8.3, 

 and 7.2 (10). Diffuses more rapidly than B or C 

 (7). Acid hydrolj'sis products include j3-lysine, 

 "roseonine" (streptolidine), and a-D-glucosa- 

 mine (8, 9, 11-13). (See Table 43 for Rf values 

 of components.) Partial structure of roseothricin 

 (13): 



— O- 



-O- 



N- 



o- 



— C— CHoNH- 



CH,— CH— CH— CH— CHCHHN— '' J L._ 



I I I \N/ ^'^ 



O NH H 



CO— CHo— CHCH.— CH.— CH-: 



' I ' I 



NH, NHo 



2— C0- 

 — NH- 



— O— 

 6H 



H 107 is very closely related to or identical to 

 roseothricin (1). 



Method of extraction: Impurities in broth pre- 

 cipitated by acidification. Filtrate adsorbed on 

 charcoal at pH 8.0. Eluted with 10 per cent acidic 

 (H2SO4) acetone. Eluate adjusted to pH 4.0. 

 Addition of 0.5 per cent sodium acetate and ace- 

 tone precipitates the sulfate. Reprecipitated as 

 picrate, which is recrystallized from hot 50 per 

 cent ethanol or methanol. Conversion to hvdro- 



Biological activity: Couiplex: Active on gram- 

 negative and gram-positive bacteria. Partial 

 cross-resistance with streptothricin; none with 

 streptomycin (1, 6). Resistance develops slowly 

 (2). Active in mice on Shigella Jlexneri, Sh. sonnet, 

 and Sal. enteritidis (6). Component A is less ac- 

 tive than a B-C mixture (7), but has the same 

 activity qualitatively (6). 



Toxicity: Complex: LDsn (mice) 14 mg per kg 

 intravenouslv. Roscalhricin .1 hydrochloride: T;Dr.n 



