DESCRIPTIONS OF ANTIBIOTICS 



215 



Yellowish brown powder. Soluble in alcohols, 

 acetone, glacial acetic acid, methyl Cellosolve, 

 and ethylene glycol. Slightly soluble in benzene 

 and dioxane; insoluble in water at any pH, chloro- 

 form, esters, ether, and petroleum ether. Ultra- 

 violet absorption spectrum maxima at 359. 380, 

 and 402 m^. Slightly positive Molisch and Fehling 

 tests. Negative FeCU test. Blue-violet color in 

 concentrated H2SO4 . Unstable at acid pH. Does 

 not contain S. 



Biological activity: Active on fungi and yeasts. 

 Activity affected by cysteine but not glucose. 



Toxicity: LDoo (mice) 5 mg per kg intrai)eri- 

 toneally. 



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

 (Japan) 9B: 79-80, 1956. 



Aiireolic Acid 



Produced by: Streptomyces sp. 



Method of e.r traction: Extraction of broth-filtrate 

 with a mixture of butanol and chloroform. Con- 

 centration of solvent in vacuo. Concentrate applied 

 to a column of Florisil which is washed with chlo- 

 roform to remove impurities. Elution of antibiotic 

 with 20 per cent methanol in chloroform. Concen- 

 tration in vacuo to amorphous yellow-tan powder. 

 Powder is dissolved in methanol; upon addition of 

 chloroform, crystallization of a magnesium salt 

 of the acid begins. 



Chemical and physical properties: Weak acid, 

 yellow. Tentative formula of magnesium salt : 

 (C56-6oH96-io4029-3i)2 Mg. [a]n, = -f(iS° (1 per ceut 

 in methanol). Soluble in lower alcohols and ace- 

 tone; moderately soluble in water, ethyl acetate, 

 and ether. Negative Fehling and anthrone tests; 

 not decolorized by sodium hydrosulfide. Positive 

 FeCls test; positive test with tyrosine reagent. 

 Ultraviolet light-absorption maxima for the mag- 

 nesium salt in 0.01 A' NaOH at 235 and 280 ni/j. 



Biological activity: Active against certain gram- 

 positive bacteria; limited activity against Tricho- 

 monas vaginalis. No activity against gram-nega- 

 tive bacteria, mycobacteria, fungi, or viruses. 

 Limited activity against Streptococcus pyogenes in 

 vivo. 



Toxicity: LD50 (mice) 2.5 to 5 mg per kg intra- 

 venously. A do.se of 0.25 mg per kg is fatal to rab- 

 bits and dogs. Low oral toxicity, suggesting lack 

 of absorption. 



Reference: 1. Grundy, W. E. et al. Antibiotics 

 & Chemotherapy 3: 1215-1220, 1953. 



Aureotliricin 



Produced by: Streptomyces thioluteus (6), S. 

 farcinicus (4), S. celluoloflavus (7), <S. cyanojiavus 

 (16), and other Streptomyces spp. (8, 15). 



Synonym: Farcinicin (4). 



Remarks: Has the nucleus 3-amino-5-methyl- 

 pyrrolin-4-ono-(4,3-D)-l,2-dithiole in common 

 with thiolutin (11). Reported to be produced 

 simultaneously with thiolutin by one of these 

 cultures (15). 



Method of extraction: Ethyl acetate extract of 

 broth and nixcclium concentrated in vacuo, de- 

 hydrated with anhydrous Na2S04 , and chro- 

 matographed on an alumina column. Column de- 

 veloped with ethyl acetate-ether (1:1). Active 

 yellow fraction concentrated in vacuo until crys- 

 tals appear, then chilled for 24 hours. Recrystal- 

 lized from ethyl acetate (1, 11). 



Chemical and physical properties: Golden-yellow 

 "thready" crystals (1). Sublimes at 200°C; de- 

 composes at 254°C (uncorrected) (2, 3) or m.p. 

 260-270°C (decomposition) (9). Insoluble in water; 

 slightly solui)le in ethyl acetate, butyl acetate, 

 acetone, benzol, ether, and ethanol. X„kix 248 

 {e = 6100), 312 (f = 3900), and 388 (e = 11,000). 

 Infrared spectrum data given in reference 5. Green 

 color in concentrated HCl after 24 hours. CaHm- 

 N2O2S2 (1, 2, 3, 5, 9). Structural formula (9) given 

 in Chapter 6. 3-Propionamido derivative of 3- 

 amino-5-methylpyrrolin-4-ono-(4,3-D)-l,2-dithi- 

 ole. Acid hydrolysis yields pyrrothine, CeHe- 

 N2OS2 , a weak amine isolated as the hydrochlo- 

 ride (pKa' 2.9), which gives a red color with 

 glutaconic aldehyde and is also a hydrolysis prod- 

 uct of thiolutin (11). 



Biological activity: Active on gram-positive and 

 gram-negative bacteria (2), as well as a variety of 

 fungi and bacteria pathogenic for plants (13). 

 Inhibits growth of ascites cells of Ehrlich car- 

 cinoma in mice, but does not prolong the survival 

 period (12). Promotes chick growth at 15 mg per 

 kg of ration (10). 



Toxicity: More toxic than chloramphenicol (2). 

 Kills HeLa cells at 2.5 /xg per ml (14). 

 References: 



1. Maeda, K. Japan. Med. J. 2: 85-88, 1949. 



2. Umezawa, H. et al. J. Antibiotics (Japan) 



2: 107-111, 1949. 



3. Maeda, K J. Antibiotics (Japan) 2: 795- 



796, 1949. 



4. Hata, T. et al. J. Antibiotics (Japan) 3: 



312-325, 1950. 



5. Celmer, W. D. et al. J. Am. Chem. Soc. 



74: 6304-6305, 1952. 



6. Okami, Y. Thesis, Hokkaido University, 



1952 (as given in Washizu, F. et al. J. 

 Antibiotics (Japan) 7A:60, 1954). 



7. Nishimura, H. et al. J. Antibiotics (Japan) 



6A: 57-65, 1953. 



