208 CHEMICAL NATURE OF ANTIBIOTIC SUBSTANCES 



As fer gillie Acid 



Aspergillic acid is produced by A. flavus. It is extracted from the 

 tryptone medium by adsorption on norite and elution with ether. The 

 pure acid has an m.p. of 93° C. (84° to 96° C.) and an optical activity 

 of [a]D = +i4°. The formula C12H20O2N2 has been proposed for 

 this substance. It possesses a hydroxyl group which gives it its acid na- 

 ture (/)K 5.5). It is stable under acid and alkaline conditions and can 

 be distilled with steam or in vacuo without loss of activity. When grown 

 in brown-sugar-containing media, a closely related substance is formed, 

 having the formula C12H20O3N2 and an m.p. of 149° C, with lower 

 biological activity. It can also be extracted from the medium, at low 

 ^H, by organic solvents (benzene or heptane). The pure aspergillic 

 acid (m.p. 96.5° to 97.5° C.) was found to account for only 5 per cent 

 of the yield, whereas another fraction (m.p. 118° to 121° C.) had 

 about 75 per cent of the antibiotic activity of the medium (102, 220). 



Aspergillic acid is moderately active against various gram-positive 

 and gram-negative bacteria, including S. aureus y E. coli, and M. tuber- 

 culosis, as well as fungi. The addition of blood to the medium greatly 

 reduces this activity. However, the antibiotic potency and the toxic 

 effect rapidly disappear after systemic or intrathecal administration, the 

 material being excreted in the urine in very small amounts (102). The 

 addition of cobaltous ions (i:ioo,ooo) greatly enhances the tubercu- 

 lostatic properties of aspergillic acid, especially in media low in iron 



(349). 



Bromo-aspergillic acid is 8 to 10 times as active against S. hemolyticus 

 as aspergillic acid. Further studies of the chemical nature of the mate- 

 rial showed it to be a pyrazine derivative (220). 



Citrinin 



Citrinin is produced by P. citrinum and other fungi ( 745 ) on a syn- 

 thetic medium, with inorganic salts of nitrogen and with glucose as a 

 source of carbon. The culture filtrate is acidified with HCl, and the sub- 

 stance crystallized from boiling alcohol. Citrinin forms a monosodium 

 salt which, at ^H 7.0 to 7.2, gives a virtually colorless solution in water. 

 It is a yellow crystalline solid, m.p. 170° to 171° C. (decomp.). It is 



