275 Tetracycline, Analogues and Related Substances 



from this portion of the molecule are not satisfactory for the 

 clarification of the origin of the A-ring. It remains to be seen 

 whether or not a less direct mechanism of acetate incorporation 

 prevails in this area. 



The isolation and identification of oxytetracycline-X (2-acetyl- 

 2-decarboxamidooxytetracycline), a lower potency antibiotic, 

 from cultures of Streptoviyces rimosus, the Terramycin pro- 

 ducer, seem to support in a general way the idea of the acetate 

 derivation of ring A. It is tempting to speculate that oxytetra- 



CHj CH3 



CH3 OHOH^N 



cycline-X may be a precursor of oxy tetracycline, but this has not 

 been proved. 



With the acetate theory as a guide, it is possible to extrapolate 

 some predictions from the tetracyclines isolated and character- 

 ized to date. It would seem probable that other mutations of 

 the producing organisms might be obtained in which one minor 

 biosynthetic step is blocked. Thus, retention of an oxygen atom 

 at position 8 might be expected. Similarly, other tetracyclines 

 lacking the Cfi-methyl and/or hydroxyl groups, the Ci2a-hydroxyl 

 group and perhaps the N-methyl groups may be found. It is 

 also possible that glycosides may be isolated as in the pyrromy- 

 cinones. 



The pyrromycinones are produced by streptomyces species, 

 and they bear some resemblance to the tetracyclines. The four 

 linear rings appearing in various states of oxidation and the 

 similarity in the number of carbon atoms make it seem that 

 their biogenetic origin may be similar to that of the tetracy- 

 clines. Apparently no experimental work has been published 

 on this point. There is probably a close relationship among the 

 pyrromycinones, rhodomycinones and quinocyclines. All of 

 these pigments are found occasionally as glycosides, but no 

 tetracycline glycosides have been reported yet. 



The rhodomycins are a complex of red pigments produced 

 by Streptomyces purpurascens. The original complex was sepa- 



