210 CHEMICAL NATURE OF ANTIBIOTIC SUBSTANCES 



crease in antibacterial activity. The introduction of an OH or the re- 

 placement 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. coli (325, 697). 



Clavacin 



Clavacin is anhydro-3-hydroxy-methylene-tetrahydro-Y-pyrone-2- 

 carboxylic acid (Figure 18). It is produced by a number of fungi, and 

 has also been designated claviformin, patulin, clavatin, and expan- 

 sin. It is colorless, optically inactive, neutral, and readily soluble in 

 water and most common organic solvents (445, 489) j it has an m.p. of 

 111° C. It is isolated either by preliminary adsorption on norite fol- 

 lowed by removal with ether or chloroform, or by the direct treatment 

 of the culture with ether. The extract is evaporated, leaving a brown 

 substance J this is treated with a small amount of water, and the aqueous 

 solution again extracted with ether. Clavacin crystallizes when the 

 ether solution is concentrated, or after preliminary purification over a 

 silica gel column. 



Clavacin is about equally active against gram-positive and gram- 

 negative bacteria, its growth inhibition being about 200,000 dilution 

 units. It is also strongly fungistatic. It is toxic to animal tissues, its 

 lethal action upon mice being about 25 mg. per kilogram body weight 

 when given intravenously or subcutaneously. 



Clavacin neutralizes the action of tetanus toxin and can thus be dis- 

 tinguished from isoclavacin and its derivatives. This specific action was 

 ascribed (739a) to the position of one double bond in clavacin. 



Fumigacin 



Fumigacin is produced by different strains of A. jumigatus. It is a 

 colorless, monobasic acid, m.p. 212° C, /-rotatory in chloroform. It is 

 insoluble in water except as sodium salt, sparingly soluble in methyl 

 and ethyl alcohols, and readily soluble in acetone, ether, chloroform, 

 and other organic solvents. It is extracted from the medium either by 

 preliminary adsorption on charcoal followed by treatment with ether 

 and alcohol, or by direct extraction of culture in accordance with the 

 following method (631) : The culture filtrate is acidified to ^H 2 with 



