FORMATION OF LIPOPHILIC ION-PAIRS BY DERIVATIVES OF PAMAMYCIN

Pamamycin, an antibiotic from Streptomyces aurantiacus forms lipophili c ion pairs but high parenteral toxicity excludes its use as a penetra tion enhancer for pharmaceuticals. A series of pamamycin derivatives w as synthesized by hydrolysis of the macrodiolide ring, derivatization of the dimethylamino moiety, and coupling the latter with bioactive sy nthons of fungal origin such as phomalacton and penicillins to form hy brid structures. Substitution of the carboxyl group of the dimethylami no moiety by less polar substituents improved ion pair formation up to the capacity of the entire pamamycin molecule.