DESCRIPTIONS OF ANTIBIOTICS 



235 



contain aspartic acid, glutamic acid, glycine, 

 threonine, alanine, tyrosine, valine, leucine, phen- 

 3'lalanine, arginine, and three unidentified nin- 

 hydrin-positive spots. Electrophoresis reveals the 

 ])resence of three components. Strong end-absorp- 

 tion in ultraviolet light, with a shoulder at 255 to 

 260 niju. Infrared absorption curve given in refer- 

 ence 1. 



Biological urtivity: Active against D. pneu- 

 moniae, Shigella dysenteriae, and Sacch. sake at 

 the level of 10 ng per ml. Not active on other bac- 

 teria and fungi tested. Active against strain Naka- 

 yama of Japanese B encephalitis virus in mice. 



Toxicity: LD50 (mice) 31 mg per kg intrave- 

 nously, 55 mg per kg intraperitoneally, 161 mg per 

 kg subcutaneously, and more than 1000 mg per 

 kg orally. 



Reference: 1. Matsumae, A. J. Antibiotics 

 (Japan) 13A: 143-154, 1960. 



CerevioccicUii 



Produced by: Streploniyces sp., closely related to 

 S. cacaoi. 



Method of extraction: Absorbed on charcoal at 

 pH 4.3 and eluted with 80 per cent acjueous acetone, 

 pH 7.4. Eluate adjusted to pH 6.4 with HCl, 

 concentrated, and extracted with ethyl acetate. 

 The acetate is evaporated to dr\-ness and the resi- 

 due taken up in a small amoxuit of chloroform. 

 Filtered chloroform solution chromatographed 

 on alimiina, which is eluted first with chloroform 

 and then with methanol, the latter removing 

 another antibiotic present. Chloroform solutions 

 combined with ligroin, chromatographed on alu- 

 mina, and eluted with methanol. Methanol eluate 

 combined with the chloroform solution that has 

 been passed through the column and evaporated. 

 The antibiotic separates and is recrystallized from 

 hot ethyl alcohol. 



Chemical and physical properties: Colorless 

 needles; m.p. 249-250°C (decomposition). Soluble 

 in methanol. Insoluble in ethanol, acetone, ethyl 

 acetate, ether, chloroform, and benzene. Sparingly 

 soluble in water. No characteristic ultraviolet 

 absorption spectrum. pK = 4.5 (50 jjcr cent meth- 

 anol). C22H39N5O4 . Calculated: C = 58.12%; 

 H = 8.74%; N = 16.0%,; Found: C = 57.76%; 

 H = 8.79%; N = 16.01%. Positive Janovsky nitro- 

 group reaction; negative Tollen, biuret, Fehling, 

 ninhydrin, Sakaguchi, maltol, and glucosamine 

 tests. 



Biological activity: Active on certain yeasts. Not 

 active on representative bacteria, M. tuberculosis 

 607, or ('. albicans in concentrations of 10 ng per 

 ml. 



Toxicity: Mice are killed l)y an intravenous in- 

 jection of 150 mg. 



Reference: 1. Yamashita, S. et al. J. Antil)iotics 

 (Japan) 8A: 42-43, 1955. 



Chartreusin 



Produced by: Streptomyces chartreusis (1, 7), 

 Streptomyces sp. (1,8), Streptomyces sp. resembling 

 S. chartreusis (9), Streptomyces sp. resembling S. 

 viridis or S. viridochromogenes (3, 4, 6), and Strep- 

 tomyces I'iridochromogenes (2, 5). 



Synonyms: Antibiotic X 465A (9, 10); antibiotic 

 747 (3); antibiotic 6A36 (2); antibiotic C 72 (8); 

 antibiotic 1293 (5). 



Method of extraction: I. Mycelium extracted 

 with 80 per cent acetone; broth-filtrate extracted 

 with chloroform. Combined extracts concentrated 

 to dryness in vacuo. Crystallized from acetone. 

 Recrystallized from acetone-water. Sodivmi salt 

 crystallized from water (1). II. Mycelium ex- 

 tracted with aqueous butanol; broth-filtrate ex- 

 tracted with butanol-butyl acetate (1:1). 

 Extracted into water at pH 9.0 to 9.2, then back- 

 extracted into chloroform at pH 3.0 to 3.5. Con- 

 centrated extract purified by (a) removal of sol- 

 vent and recrystallization from benzene -ligroin; 

 or (b) removal of solvent, then chloroform solu- 

 tion of residue chromatographed on anhydrous 

 calcium hydrophosphate and eluted with acetone- 

 chloroform (1:3). Active fractions crystallized 

 from aqueous acetone or acetone-ligroin (2). III. 

 Broth-filtrate extracted with chloroform. Crude 

 residue from acetone crystallized from acetone or 

 aciueous acetone (6). IV. Broth and mj^celium 

 extracted with methylene chloride. Extract con- 

 centrated in vacuo, filtered, then reconcentrated. 

 Addition of ethanol to boiling solution precipi- 

 tates the antibiotic. Recrystallized from methyl- 

 ene chloride-ethanol (9). 



Chemical and physical properties: Weakly acidic, 

 glucosidic substance. Anhydrous chartreusin: Thin 

 greenish yellow plates (3, fi, 9) or yellow prisms 

 (2); m.p. 184-187°C (2, 3, 6, 9). Comparison of 

 products from references 1, 3, 6, and 9 shows no 

 depression of mixed melting points. Other charac- 

 teristics are identical (9, 10). Soluble in chloro- 

 form, less so in acetone, slowly soluble in NaHCOg 

 solution. More soluble in dilute acid than water. 

 Soluble with inactivation in NaOH and Na2C03 

 solutions (3, 6). Ultraviolet absorption spectrum 

 maxima at 236, 266, 334, 380, 401, and 424 m^i (95 

 per cent ethanol) (6, 9). Slight differences in ultra- 

 violet spectrum were noted (1, 2). Infrared spec- 

 trum given in references 1 and 2. [q]„ = +127.5° ± 

 10° (c = 0.3 per cent in p\ii(line) or —36.2° ± 4° 



