DESCRIPTIONS OF ANTIBIOTICS 



393 



2 hours. Precipitate thus formed is washed with 

 water and extracted with 80 per cent acetone. 

 Acetone-extract evaporated and water remaining 

 is freeze dried. Crude antibiotic purified by frac- 

 tional precipitation from a methanolic solution 

 using ethyl ether, or by countercurrent distribu- 

 tion. 



Chemical and physical properties: Probably an 

 organic acid with no sulfur or phenyl groups. 

 Countercurrent (butanol-pH 6.05 sodium phos- 

 phate buffer) and chromatographic studies (buta- 

 nol-20 per cent sodium phosphate) indicate a 

 single entity. Stable at pH 2 to 8 at 37°C for 21 

 hours. At pH 10, 50 per cent of activity lost after 8 

 hours. Biuret, ninhydrin, xanthoproteic, Molisch, 

 and lead acetate (for sulfur) tests negative. Di- 

 alyzable. Precipitated with saturated ammonium 

 sulfate. Ultraviolet absorption maximum at 268 to 

 272 ran in water. 



Biological activity: Active primarily on gram- 

 positive bacteria, including Clostridium. Not 

 active against mycobacteria, fungi, or Nocardia. 



Toxicity: Intraperitoneal injection of 32 mg (25 

 units per mg) into 209 mice had no toxic effect after 

 3 weeks of observation (1 unit = minimal amount 

 of thermoviridin per ml which inhibits growth of 

 Staph, aureus 209P in broth for 24 hours at 37°C). 



Reference: 1. Schuurmans, D. M. et al. Appl. 

 Microbiol. 4:61-66,1956. 



Thioauriii 



Produced by: Streptomyces sp. (1, 2). 



Synonyyn: Antibiotic HA 9 (2). 



Method of extraction: Filtered broth extracted 

 with ethyl acetate. I. Extract concentrated in 

 vacuo, water added, and remaining ethyl acetate 

 evaporated off. II. Tarry aqueous suspension 

 decanted, after standing overnight. Residue ex- 

 tracted with carbon tetrachloride or chloroform. 

 Extract back-extracted with water. Water ex- 

 tracted again with ethyl acetate and step II 

 repeated. On cooling, crystals precipitate. Purifi- 

 cation by countercurrent extraction (ethyl ace- 

 tate-water) or by chromatography on silica gel 

 from chloroform and development with ethyl 

 acetate. Recrystallized from acetone or ethyl 

 acetate (1, 2). 



Chemical and physical properties: Neutral yellow 

 crystals; m.p. 175-181°C (decomposition) (1, 2). 

 At a pressure of 0.05 mm, sublimes very slowly at 

 110-140°C (m.p. of sublimate, 176-177.5°C) (2). 

 Ci4Hi204N4S4 : C = 38.98%; H = 2.89%; N = 

 12.90%; S = 29.41% (1). Or C7H6N2O2S2 : C = 

 39.13%; H = 2.91%; N = 12.29%; S = 30.05% (2). 

 Ultraviolet absorption spectnmi maxima at 232 



and 370 niju (in 0.5 M HCl or methanol) and at 300 

 niM (in 0.5 M NaOH) (1,2). Heating in boiling 6 

 N HCl gives a dihydrochloride in the form of 

 biologically active, yellow plates; m.p. 210-215^C 

 (decomposition). Oxidation with 30 per cent H2O2 

 gives a yellow, biologically inactive, crystalline 

 product; m.p. 205-210°C (1). Optically inactive 

 Negative FeCli test. Insoluble in water and chlo- 

 roform; slightly soluble in ethyl acetate and ben- 

 zene; fairly soluble in methanol. Rf on paper 

 chromatography (wet n-butanol) = 0.7 to 0.79 (2). 

 Crystallographic and infrared data given in refer- 

 ence 3. 



Biological activity: Moderately active on gram- 

 positive and gram-negative bacteria, and on some 

 fungi and yeasts (1, 2). Activity not diminished 

 by serum or cysteine. 



Toxicity: LD50 (mice) 15 to 16 mg per kg intra- 

 venously, 20 mg per kg subcutaneously (1, 2). 



References: 



1. Bolholfer, W. A. et al. Antibiotics & Chem- 



otherapy 3: 382-384, 1953. 



2. Eisenman, W. et al. Antibiotics & Chem- 



otherapy 3: 385-392, 1953. 



3. Eisenman, W. and Minieri, P. P. U. S. 



Patent 2,749,273, June 5, 1956. 



Thiolutin 



Produced by: Streptomyces albus (1, 12j, iS. cellu- 

 loflavus (U), Streptomijces sp. (21) (the latter cul- 

 ture produces aureothricin simultaneously) . 



Synonym: Has the same 3-amino-5-methylpyr- 

 rolin-4-ono-(4,3-d)-l,2-dithiole nucleus as aureo- 

 thricin (18). 



Method of extraction: Whole culture adjusted to 

 pH 2.0, heated at 90°C for 20 minutes, pH re-ad- 

 justed to 3.5, and the broth filtered using a filter- 

 aid. Filtrate extracted with n-butanol, chloroform, 

 methyl isobutyl ketone, ethyl acetate, benzene, or 

 chloroform. Extraction can also be carried out at 

 neutrality. Extract concentrated, then recrystal- 

 lized from methanol, n-butanol, or dimethyl- 

 formamide (12). 



Chemical and physiccd properties: Neutral, op- 

 tically inactive yellow crystals; m.p. 270°C (de- 

 composition) (15). Sublimes without decomposi- 

 tion when heated at 200°C in vacuo (18) . Soluble 

 in butanol, dimethylformamide, chloroform, iso- 

 propanol, ethanol, methanol, acetone, glacial 

 acetic acid, methyl isobutyl ketone, and pyridine. 

 Limited solubility in petroleum ether, hexane, 

 water, ether, and benzene (1, 12). X'L'?x^388 mM,with 

 minor peaks at 311 and 250 m/x- Infrared spectrum 

 given in reference 18. Optically inactive in glacial 

 acetic acid (12). Stable in acidic and neutral solu- 



