The synthesis of amides of polyene macrolide antibiotics.

groups activated under the treatment with diphenyl phosphorazidate7) and triethylamine or N,N'-dicyclohexylcarbodiimide and I-hydroxy1 H-benzotriazole mixtures. The reaction was carried out in N,N-dimethylformamide or N,Ndimethylacetamide, at room temperature, using an excess of the reagents. The course of the reaction was followed by means of thin-layer chromatography on silica gel with the solvent system: chloroform methanol water in volume proportions depending on the antibiotic and amine applied. Derivatives of polyene antibiotics representing different structural groups (pimaricin, polyfungin, amphotericin B and aureofacin) were synthesized and characterized. In the ultravioletvisible spectra of the amides of polyene macrolides the position of the absorption maxima and their relative intensities are identical with those of the parent antibiotics. The presence of the amide bonds were confirmed by their IR spectra. Absorption maxima of the amide carbonyl ranged from 1600 cm -1 to 1675 cm -1. The molecular weights of the synthesized derivatives were measured by means of field desorption mass spectrometry. In an exampler synthesis, 665 mg of pimaricin (E1%1cm=1,000 at 304 nm) was suspended in 20 ml of N,N-dimethylacetamide and 1 ml of butylamine, 2.15 ml of diphenyl phosphorazidate and 1.4 ml of triethylamine were added with stirring and the mixture was kept at room temperature for 4 hours in darkness. The product