50 



NATURE, FORMATION, AND ACTIVITIES 



which has activity against tumor colls and a 

 few gram-positive bacteria. 



Acetomycin is a neutral saturated acetoxy 

 lactone, 



CH3 CH3 



-COCH, 



/ 



CH3CO— o 



o 



\ 



o 



which is moderately active against myco- 

 l)acteria and protozoa. 



Azomycin is 2-nitro-imidazole, 



,1 N 



NO2 



This antibiotic, which contains an ecjual 

 number of molecules of nitrogen and carbon, 

 is active mainly against bacteria. 



Cycloseriyie is a ketoaminoisoxazole, which 

 is active mainly against mycobacteria: 



HsNr 



-,=0 



.N 



O 



The chemical structure of cycloserine was 

 identified as D-4-amino-3-isoxazolidone. On 

 acid hydrolysis, it gives hydroxylamine and 

 serine. Its biogenetic relationship to alanine 

 has also been suggested (Abraham and 

 Newton, 1958). Its synthesis has been 

 brought about, as summarized by Van 

 Tamelen (1958). 



Another antibiotic with activity only 

 against mycobacteria is actithiazic acid, a 

 keto thiazole with an aliphatic acid chain in 

 position 2: 



0= 



-N 



-(CH.2)5COOH 



It is 4-thiazolidone-2-caproic acid. It is 



soluble in organic solvents and its sodium 

 salt is soluble in water. It has been syn- 

 thesized, the racemate having about half 

 the activity of the natural levo form. The 

 toxicity is low, but the antibiotic is not 

 active in vivo l)ecause of the presence of 

 biotin, which interferes with its activity 

 (Grundy r/ a/., 1952). 



Cyclohexi 111 ides 



This is a group of antibiotics containing a 

 glutarimide moiety. Of these, the antifungal 

 agent cydohcximide has been known for the 

 longest time: 



CH, 



CH3 



=0 

 CHOHCH. 



O 



/ 



NH 



\ 

 O 



Its molecule has four centers of asymmetry. 

 Some of the isomers of cycloheximide have 

 been studied; they have been foimd to have 

 less biological activity than the mother com- 

 pound. One of the eight possible dehydro- 

 cycloheximides, inactone, has no biological 

 activity. Four substances which have been 

 studied mainly because of their antitumor 

 activity, strcptovitacins A, B, and (' and 

 antitumor .substance E 73, have the same 

 molecular skeleton as cycloheximide. Their 

 structural formulas will be found in Part B 

 of this book. 



Stre-ptimidone is an antifungal-antipro- 

 tozoal antibiotic which also has a glutarimide 

 moiety to which an aliphatic chain is at- 

 tached: 



CH.CHCCH.CHCHCHs 



O 



COCH.CHOHCH/ NH 



_/ 

 \ 

 O 



