294 



DESCRIPTIONS OF ANTIBIOTICS 



10. Yoshida, R. and Tsununa, M. J. Aiiti 



biotics (Japan) lOA: 177, 1957. 



11. Welch, H. et at. Antibiotics Ann. 337- 



341, 1958-1959. 



12. Steinberg, B. A. et ul. Antibiotics Ann. 



342-345, 1958-1959. 



Leucomycin B 



Produced by: Streptomyrcs kitasatoensis (1). 



Remarks: Produced in broths coincidentally 

 with leucomycin. 



Method of extrortion: Filtered Ijroth extracted 

 with benzene or butyl acetate at pH 8.0. Back- 

 extracted into dilute HCl (pH 4.0), washed with 

 butyl acetate, and adjusted to pH 8.0 with 1 N 

 NaOH. Alkaline solution extracted with benzene. 

 After concentration of the extract to a small vol- 

 ume, carbon is added. Elution from carbon with 

 hot benzene. Benzene solution concentrated /// 

 vacuo. Leucomycin B precipitated in the cold. 

 Recrystallized from atiueous ethanol. Differen- 

 tiated from leucomycin by paper chromatography 

 (ether) (1). 



Chemical and physical properties: White needles; 

 m.p. 192-193°C. Basic compound. Relatively in- 

 soluble in water. Soluble in ether, acetone, chloro- 

 form, ethyl acetate, butyl acetate, and benzene. 

 Acid salts are water-soluble, [afo = —49.6° (c = 

 2 per cent in ethanol). C4iH69NOi6 : C = 59.34%; 

 H = 8.31%; N = 1.65%; O = 30.71%, l)y differ- 

 ence. Ultraviolet absorption spectrum maximum 

 at 232 niju (£'/cm 325). Infrared absorption spec- 

 trinn given in reference 1. Biologically active de- 

 rivatives include acetyl leucomycin B (I), the 

 thio.semicarbazone (II), 2,4-dinitrophenylhydra- 

 zone (III), and isonicotinic hydrazone (IV) (1). 



Biological activity: Leucomycin B is active on 

 gram-positive bacteria and relatively inactive on 

 mycobacteria, gram-negative bacteria, fungi, 

 Candida, and Nocardia asteroides. Derivatives I, 

 II, III, and IV are active on gram-positive bac- 

 teria and mycobacteria. 



Reference: 1. Sano, Y. J. Antibiotics (Japan) 

 9: 202-206, 1956. 



Leucomycin- like Complex 



Produced by: Strepiomyces sp. with some simi- 

 larities to <S. kitasatoensis. 



Synonym: Antibiotic 6, 237 R.P. 



Method of extraction: Broth-filtrate extracted 

 with amyl acetate at pH 8. Extract treated with 

 acidic water. Readjustment to alkaline pH and 

 extraction with ethylene dichloride. Evaporation 

 gives crude substance. Purification by counter- 

 current distribution (isopropyl ether-0.062 M 



phosphate i)uft'er i)H 6.5, 1:1) and chromatog- 

 rajihy on alumina from benzene. 



Chetnical and physical properties: Complex sub- 

 stance composed of two bases. Base I: m.p. 139- 

 140°C. [a]c. = —78° (c = 1 per cent in methanol). 

 C = 60.5%; H = 8.5%; O = 27.8%; N = 1.85%. 

 pKi, = 7.1. LHtraviolet absorption spectrum max- 

 ima at 231 mix (£'!";„, 311) and 279 m^i {El^ln, 6.3). 

 Rf = 0.03 (stationary phase: disodium phosphate; 

 mobile phase: cyclohexane-methyl isobutyl ke- 

 tone, 85:15). Base II: m.p. 144°C. [a]f = -75° 

 (c = 1 per cent in methanol). C = 60.5%; H = 

 8.4%; () = 29.3%; N = 1.6%. pK,, = 7.1. Ultra- 

 violet absorption spectrum maxima at 231 m/x 

 (E'l'L, 348) and 279 mM (EW, 2.3). Rf = 0.15 (sys- 

 tem given above). Leucomycin contains more 

 Base I than Ba.se II. The reverse is true in this 

 complex. A third base, present in the original 

 leucomycin, is not present in this complex. 



Biological activity: Active on gram-positive bac- 

 teria. Not active on gram-negative bacteria, ex- 

 cept Neisseria, Pasteurella, etc. Cross-resistance 

 with erythromycin and carbomycin. Active in 

 mice on streptococcal, i)nevunococcal, and staph- 

 ylococcal infections. 



Toxicity: LDso (mice) about 2 gm i)er kg sul)- 

 cutaneously, >5 gm per kg orally. 



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

 ])iol. 2: 76-90, 1956. 



Levomycin 



Produced by: Streptomyces sp. 



Synonyms: Similar to actinoleukin and anti- 

 biotic F 43. 



Method of extraction: l^xtracted from broth at 

 all pH values by ethyl acetate, n-butyl alcohol, 

 or ether. A pigmented impurity can be removed 

 by treatment of the concentrated ethyl acetate 

 extract in the cold with 0.01 A' NaOH. Precipi- 

 tated from washed and concentrated ethyl ace- 

 tate solutions by petroleum ether or n-hexane. 

 Purification by covmtercurrent distribution 

 (methanol-l)enzene-water, 5:5:1 ). Crystallization 

 of most active fraction from cold chloroform- 

 ethanol. Chromatograj^hy over silicic acid in 

 chlorof orm-methanol . 



Chonical and physical properties: Colorless 

 prisms; m.p. 222-224°C. Co-H.^sN^Om : C = 

 54.05%; N = 13.90%; H = 6.35%. Very soluble in 

 chloroform and pyridine; less so in carbon tetra- 

 chloride, ethyl acetate, and hot alcohols. Slightly 

 soluble in ether, benzene, cold alcohols, acetone, 

 and (lioxane. Insoluble in water, petroleum ether, 

 5 per cent aqueous HCl, and NaOH. Soluble in 

 cold 6 -V HCl with slow decomposition. [a\u = 



