Antibiotic X-5108. IX. Chemical conversion of mocimycin to aurodox and derivatives of aurodox, goldinamine and mocimycin.
Mocimycin was converted to the acylesters by selective acylation of the hydroxyl group of the 4-hydroxy-1-methyl-2(1H)pyridinone moiety. Subsequent N-methylation at the nuclear nitrogen and removal of the protective group from the resulting reaction products afforded aurodox. Mono-O-acetylmocimycin and several analogous aurodox esters thus prepared possess antibacterial activity in vitro and growth-promotion properties in poultry. Esters of aurodox involving the hydroxyl group of the 4-hydroxy-1-methyl-2(1H)pyridinone moiety are activated. Accordingly, acetic acid treatment of the aurodox esters generates O-acylgoldinamines which undergo transacylation furnishing N-acylgoldinamines. Alternatively, N-acylgoldinamines can be prepared by selective mono--o-arylsulfonylation of aurodox, liberating o-arylsulfonylgoldinamine by treatment with acetic acid followed by N-acylation and removal of the protective arylsulfonyl group. A third approach to N-acylgoldinamines consists in direct N-acylation of goldinamine itself which is prepared by acetic acid treatment of aurodox. None of these derivatives prepared, however, exhibited significant antimicrobial or growth-promoting properties, suggesting that goldinonic acid moiety, or a closely related derivative thereof, is required for biological activity.
D000215:Acylation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000899:Aurodox / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D001419:Bacteria / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D002645:Chickens; D006128:Growth / Q000187:drug effects; D011728:Pyridones; D013268:Stimulation, Chemical
D000900:Anti-Bacterial Agents; D011728:Pyridones; D000899:Aurodox