Chapter 6 



Chemical Nature of the Antibiotics 

 of Actinoiiiycetes 



The known antibiotics prodiicctl by 

 actinomycetes range in complexity from 

 very simple compounds, such as nitro- 

 propionic acid (bovinocidin), to very 

 complex proteins, such as the lytic enzymes 

 of actinomycetin. Certain chemical types 

 are linked with a specific range of anti- 

 microbial activity. For example, the polyenes 

 are mainly antifungal in nature, and the ex- 

 ceptions reported in the literature may very 

 well be due to antibacterial impurities. Also 

 the streptothricins are active against both 

 gram-positive and gram-negative bacteria 

 and even fungi, whereas the nonpolyenic 

 macrolides are, as a whole, active only 

 against gram-positive l)acteria. In spite of 

 these general correlations between types of 

 structure and activity, it is not yet possible 

 to predict in all cases the range of anti- 

 microbial activit}' of an antibiotic purely on 

 the basis of its chemical structure. Likewise, 

 it is not yet possible to synthesize com- 

 pounds, the biological properties of which 

 would be known beforehand. 



In this chapter, the antibiotics are grouped 

 according to their chemical similarities. 

 More detailed information and references 

 will be found in Part B of this book and in 

 the reviews written on this subject recently 

 by Abraham and Xewton (1958), Chain 

 (1958), Van Tamelen (1958), Harman 

 (1959), and also in the Merck Index (1960). 

 From a chemical point of vi(^\v, antibiotics 



can Ije grouped according to various criteria: 

 (1) the elements contained in their mole- 

 cules, (2) the most important groupings in 

 these molecules, and (3) the structure of 

 their molecular skeleton. 



An examination of the empirical formulas 

 of the antibiotics of actinomycetes listed in 

 Part B of this Ixjok reveals that most of 

 these substances contain carbon, hydrogen, 

 oxygen, and nitrogen (153 compounds). 

 Next in frequency are substances containing 

 only carbon, hydrogen, and oxygen (31 

 compounds), followed by substances con- 

 taining carbon, hydrogen, oxygen, nitrogen, 

 and sulfur (18 compounds). This survey 

 takes into account only those substances 

 for which an empirical formula was at least 

 proposed; howe\'er, their number is probably 

 high enough to be representative of the 

 whole group. A few substances have unusual 

 elementary compositions: chloramphenicol, 

 chlortetracycline, demethylchlortetracycline, 

 and exfoliatin contain nonionic chlorine. 

 Bromine can l)e substituted for this chlorine 

 in chlortetracycline to form bromtetra- 

 cycline, and possibly a similar substitution 

 can be made in the other substances. 

 Exfoliatin contains only carbon, hj^drogen, 

 oxygen, and chlorine, whereas the other 

 antibiotics of this group contain, in addition, 

 nitrogen. Two antibiotics have unique 

 elementary composition: grisein contains 

 sulfui' and iron, and phleomycin contains 



48 



