121 



Macrocyclic Lactones (Macrolides) 



branched lactones are derived in whole or in part from acetate. 



It is obvious that in each case many modifications of the mac- 

 rolide moiety have occurred from the simplest intermediate 

 ring which could be envisaged. These include complete or 

 partial reduction of carbonyl groups, dehydration of the corre- 

 sponding secondary alcohols, epoxidation or reduction of carbon- 

 carbon double bonds, oxidation of tertiary carbon atoms, cleav- 

 age of epoxides to glycols, etc. Yet, despite the confusing detail, 

 the fundamental pattern of oxidation and reduction remains 

 apparent, just as it does in many of the metaboUtes of the myco- 

 bacteria and corynebacteria. 



It wall be interesting to see how much of the information con- 

 cerning the biogenesis of the macrolides can be transposed to 

 metabolites of the mycobacteria and corynebacteria and vice 

 versa. 



In the cases of picromycin, methymycin, erythromycin, nar- 

 bomycin and oleandomycin it is possible to follow the course of 

 alternate oxidation throughout the lactone rings wdth remark- 

 able regularity, the hypothetical intermediate being, apparently, 

 a single continuous chain, unbranched except for the methyl 

 groups. In the cases of carbomycin and pimaricin, anomalies 

 occur. These could be explained by a junction of shorter 

 chains, perhaps as shown below, in a manner similar to the for- 

 mation of corynomycolic acid by the coupling of 2 moles of pal- 

 mitic acid: 



Pimaricin 



OCOCH3 

 Lactone Portion of Carbomycin 



Another suggestion has been made in the case of carbomycin,^ 

 namely that a protocarbomycin may occur which later rear- 

 ranges by a glycol-aldehyde shift: 



