119 



Macrocyclic Lactones (Macrolides) 



OCOCH3 



In this regard it is striking that the sugar L-oleandrose occurs 

 in both oleandrin and in the macroHde oleandomycin. 



The macrolide antibiotics are most effective against gram- 

 positive bacteria. In the introduction to the section on steroids 

 and terpenoids, it was mentioned that no true steroids have 

 ever been detected conclusively in bacteria. It was noted also 

 that certain investigators exploring the utilization of mevalonic 

 acid by gram-positive bacteria (especially lactobacilli) found 

 that partially oxidized aliphatic substances with more than 15 

 carbon atoms were produced.- While these products were not 

 thoroughly characterized, the properties as described were rem- 

 iniscent of the lactone portions of the macrolides. It also has 

 been mentioned elsewhere that the general chemical structure 

 and metabolism of the actinomycetales seem to be more closely 

 related to that of the bacteria than to that of the fungi, which 

 they resemble superficially. From these premises, it is tempting 

 to speculate that the macrolide antibiotics may interfere in some 

 way with a primitive kind of hormonal or steroid metabolism 

 in gram-positive bacteria. In this connection it should be 

 noted, however, that the sugar portions of most of the known 

 macrolide antibiotics are essential to their antibacterial activity. 

 Tylosin and lankamycin may be exceptions. 



Several of the many macrocyclic lactones which have been 

 isolated from streptomycete cultures have been well character- 

 ized structurally. Complete structures have been reported for 

 picromycin, methymycin, neomethymycin, erythromycin, eryth- 

 romycin B, erythromycin C, carbomycin (Magnamycin), carbo- 

 mycin B, oleandomycin and pimaricin. A considerable amount 

 of information has been reported concerning the structures of 

 narbomycin, the foromacidins (spiramycins) and the pentaenes 

 lagosin and fiUpin.* 



The few cases available for comparison fall into a general 

 pattern. This involves the lactone of a long chain aliphatic 



- E. Kodlcek, Abstracts of the Gordon Conference on Vitamins 

 and Metabolism, 1958. 

 * See addendum. 



