208 



DESCRIPTIONS OF ANTIBIOTICS 



pyridine). C = 58.3%; H = 8.0%; O = 31.5%); 

 N = 1.65%. Ultraviolet absorption spectrum max- 

 ima at 291 niM (E'lL 562), 304 m^ (£'lcm 863), 

 and 318 m^ (Elfm 783). 



Biological activity: Active on yeasts and fvingi. 

 Not active on bacteria. More active than nj'statin. 



Toxicity: LD50 (mice) 37 mg per kg svibcutane- 

 ously, 250 mg per kg orally. 



Reference: 1. Despois, R. et nl. Giorn. micro- 

 biol. 2: 76-90, 1956. 



Antifungal Anlihiolic A 228 



Produced by: Streptomyces sp. (2). 



Method of extraction: I. Filtered l)roth ex- 

 tracted with n-butanol (or chloroform) at pH 7.0. 

 Extract concentrated under reduced pressure; 

 diethyl or petroleum ether, ethyl acetate, or ace- 

 tone added to precipitate A 228 complex. Precipi- 

 tate slurried in ether, then dried in vacuo. II. 

 Adsorbed from the whole culture-broth on 1 per 

 cent magnesium trisilicate and 2 per cent siliceous 

 earth, and eluted with acetone, then 80 per cent 

 aqueous acetone. Eluates concentrated under re- 

 duced pressure at <35°C to remove the acetone. 

 Aqueous residue extracted with n-butanol. Ex- 

 tract concentrated under reduced pressure. Pre- 

 cipitated from the residue on addition of ether or 

 petroleum ether. Purified by countercurrent dis- 

 tribution (water: n-butanol-diethyl ether, 1:1.75). 

 Two fractions, A 228a and A 228b, are separated 

 by reversed phase partition chromatography on 

 Alloprene (chlorinated rubber containing 2 per 

 cent butanol) with n-butanol-saturated water as 

 solvent and developer. Fraction A 228a is ob- 

 tained in the earlier fractions, A 228b in the later 

 (2). 



Chemical and physical properties: Complex, con- 

 taining two neutral heptaenes. Yellow-brown 

 substances. Both have the following characteris- 

 tics: Soluble in methanol, ethanol, and butanol. 

 Soluble in chloroform with loss of biological ac- 

 tivity. Very slightly soluble in water. Insoluble in 

 anhydrous acetone, diethyl ether, ethyl acetate, 

 and petroleum ether. Ultraviolet absorption spec- 

 trum maxima (aqueous ethanol) at 291, 304, 318, 

 332, and 350 m^; E]a.: (a) 150, 265, 475, 695, 700, 

 and (b) 160, 290, 520, 785, 805, respectively. Infra- 

 red data given in reference 1. Yellowish blue 

 fluorescence in ultraviolet light (aqueous solu- 

 tion). Decolorizes laromine water with the forma- 

 tion of a faintljr yellow or white precipitate. Dark 

 violet color in H2SO4 . Stable in powder form. In 

 aqueous solution, stable in the cold and compara- 

 tively stable at room temperature in the dark. 

 Photo-labile. Alcoholic solutions are more stable 



than aqueous; more stable at neutrality than at 

 acid pH. C = about 60%; H = about 8%; N = 

 about 2%; S = 4%. No halogens (1, 2). 



Biological activity: Active on yeasts and filamen- 

 tous fungi. Not active on bacteria, mycobacteria, 

 or actinomvcetes. Active on Trichomonas vaginalis 

 at 15 to 30 Mg per ml and Endamoeba histolytica at 

 60 to 120 jug per ml. No difference in antibiotic ac- 

 tivity between A 228a and A 228b (2). 



Toxicity: Two of three mice were killed by an 

 intraperitoneal injection of 83 mg per kg of A 

 228a, but 41.5 mg per kg was tolerated. Mice also 

 tolerate 100 mg per kg of A 228b (same route) (2). 

 Not absorbed from the intestinal tract (1). 



References: 



1. Peynaud, E. and Lafourcade, S. Rev. fer- 



mentations et ind. aliment. 8: 228-242, 

 1953. 



2. Ball, S. et al. German Patent 942,047, April 



26, 1956. 



Antifungal Antibiotic J 44 



Produced by: Streptomyces sp. belonging to <S. 

 fungicidicus "group G." 



Method of extraction: Broth-filtrate extracted 

 with ethyl acetate at pH 4.0. Extract concentrated 

 in vacuo, and passed through a column of alumina. 

 Water added; solvent removed in vacuo. Precipi- 

 tate filtered off, filtrate adjusted to pH 4.0, and 

 extracted with ethyl acetate. Concentration of 

 extract to yellow syrup. Chromatography on 

 alumina with methanol as solvent and developer. 

 Active fractions concentrated. Antibiotic J 4A 

 precipitated from concentrate in the cold. Re- 

 crystallization from ether-methanol. Antilnotic 

 also present in mycelivnn, 



Chemical and physical properties: White prisms; 

 m.p. 164-170°C. Soluble in ethyl acetate and diox- 

 ane. Fairly soluble in ethanol, ether, and water. 

 Sparingly soluble in chloroform and petroleum 

 ether. Ultraviolet absorption sijectrum maximimi 

 at 212 niju with a minor peak at 260 mju. C = 61 .47% ; 

 H = 7.41%; N = 5.15%; O = 25.93%. Negative 

 ninhydrin, Sakaguchi, biuret, Millon, Molisch, 

 Fehling, Seliwanoft", and P'eCls tests. Weakly 

 positive Tollen test. Gives orange color in 40 per 

 centHoSOj. 



Biological activity: Active on fungi, including 

 Aspergillus and Penicillium, but less active on 

 Trichophyton. Not active on the yeasts tested. 



Reference: 1. Taguchi, H. and Nakano, A. J. 

 Fermentation Technol. 35: 145-149, 1957. 



Antifungal \ii I ibiotic J 4B 



Produced by: Streptomyces sp. belonging to the 

 S. fungicidicus "group G." 



