Chemical Synthesis, Isolation and Characterization of α-N-Fattyacyl Colistin Nonapeptide with Special Reference to the Correlation between Antimicrobial Activity and Carbon Number of Fattyacyl Moiety

Five normal and two isofattyacyl colistin nonapeptides, of which carbon numbers of acyl moiety ranged in 9~14, were synthesized in addition to those as previously reported, and characterized on their chemical, physicochemical and biological natures. These derivatives obtained in hydrochloride salt indicated clear melting point at 200~225°C, easily dissolved in water and their optical activities were levorotatory like colistin nonapeptide and colistin. Antimicrobial spectra of the n-fattyacyl derivatives were extended in kinds of susceptible organisms to gram positive bacteria, thus n-undecanoyl, n-dodecanoyl and n-tetradecanoyl derivatives inhibited all of test organisms except Seratia marcescens and four Proteus species. As compared with antimicrobial activity of colistin, that of α-N-fattyacyl derivatives was considerably weakened to extents of 1/4~1/8 against gram negative bacteria while enforced 2~8 times against gram positive bacteria. In two isofattyacyl derivatives synthesized, their antimicrobial activities were inferior to those of corresponding normal fattyacyl derivatives. Moreover, correlation between antimicrobial activity against each test organism employed and carbon number of acyl moiety in ten α-N-fattyacyl derivatives synthesized hitherto, was investigated, and normal fattyacyl derivatives in their fattyacyl moieties of carbon number in 8~12, or rather in the range more than 10 apparently exhibited a characteristic antimicrobial profiles against gram negative and positive bacteria. Against colistin-insensitive gram negative bacteria such as S. marcescens and four Proteus species, all of α-N-fattyacyl colistin nonapeptides so far were inactive at the concentration of 100μg/ml.