182 CHEMICAL NATURE OF ANTIBIOTIC SUBSTANCES 



whereas penicillin does not inhibit this organism even in concentrations 

 of 1 : 1,000. It was found to possess antibiotic properties also against 

 yeasts, and to be toxic to animals when injected subcutaneously in con- 

 centrations of 0.2 to 0.3 gm. per kilogram weight. 



More recently, penicillic acid was isolated (661, 664) by evapora- 

 tion of the culture solution, the crude acid crystallizing on cooling. It 

 was purified by recrystallization from hot water. Yields greater than 

 2 gm. per liter of culture were obtained. The acid is a stable, colorless 

 compound which is appreciably soluble in cold water and gives a series 

 of colorless and readily soluble salts (s^j 470a). 



Penicillic acid was shown to have the constitution y-keto-p-methoxy- 

 S-methylene-A-a-hexenoic acid, which exists in both the keto and lactone 

 forms : 



CHo=CH(CH3)COC(OCH3)=CHCOOH - 



CHo=CH-(CH3)-C(OH)-C(OCH,)=CH-CO 



i o ! 



FuMiGATiN. Among the other quinones isolated from fungi, fumi- 

 gatin deserves consideration (21, 712). It is a 3-hydroxy, 4-methoxy, 

 2 : 5-toluquinone or C8H8O4 (Figure 16, page 164). 



All quinones have been divided into three groups on the basis of their 

 action on Stafhylococcus: (a) those that have a markedly weaker anti- 

 bacterial action than fumigatin, including toluquinone and some of its 

 derivatives i (b) those that are somewhat more effective than fumi- 

 gatin, including 3:4 dimethoxytoluquinone 5 (c) those with activity 

 greater than that of fumigatin (methoxytoluquinones). The introduc- 

 tion of -OCH3 into the quinone nucleus results in an increase in anti- 

 bacterial activity. The introduction of an OH or the replacement of 

 -OCH3 by OH results in a decrease in activity. None of these quinones, 

 however, has any very striking action on gram-negative bacteria, such as 

 E. coU (660). Electrode potentials of quinones have been found to be 

 unrelated to their bacteriostatic action against E. coli, but for S. aureus, 

 the reduction potentials fall within certain limits (417, 6G6). 



Clavacin is produced by A. clavatus (935), P. fatulum (patulin 

 [713]), P. clavijorme (114, 115),/*. exfansum (22), and probably a 

 number of other fungi (470). It can be isolated from the culture filtrate 



