276 



DESCRIPTIONS OF ANTIBIOTICS 



Biuloguat uctwiUj: Active on Sacch . sake and 

 C. albicans. 



Toxiciti/: LDsci (mice) 15 mg per k^ intraperi- 

 toneally. 



Reference: 1. Utahara, R. et al. J. Antibiotics 

 (Japan) 12A: 73-74, 1959. 



Fianij celiii 



Pfdilnccd bi/: Streptomyces lavendiihic (1, 2, S). 

 This strain was later identified as S. j'rudiae (13). 

 Streptomyces sp. (6). 



Synonyms: Soframycin, antibiotic K. F. 185 

 (6, 8), neomycin (14). 



Method of extraction: I. Broth-tiltrate treated 

 with sodium hexametaphosphate, pH adjusted to 

 8.5, and adsorption on IRC-50. Flnted with aciue- 

 ous 5 per cent triethyhimine or dilute HCl (pH 

 2.0). Adsorbed on triethylamine-washed IRC-50 

 under different pH conditions and eluted with 

 aqueous acidic methanol; pH of eluate adjusted to 

 5 with triethylamine, and framycetin precipitated 

 with 40 per cent triethylamine sulfate in absolute 

 methanol. Purification by chromatography on 

 alumina. Crystallized as the picrate (1, 6, 8). II. 

 Broth-filtrate adsorbed on carbon at pH 8.2. Car- 

 bon washed, then eluted with methanol-HCl 

 (10: 1 ) , followed by methanol. Added to ethyl ether 

 to precipitate framycetin (1, 8). III. Whole 

 culture adjusted to pH 3 or heated to 35-50°C, and 

 filtered. Adsorbed on carbon or silica gel at pH 7, 

 atul eluted with acidic alcohol. Eluates purified by 

 treatment with carbon, and with IR-100 at pH 4.0, 

 followed by adsorption on IRC-50. Eluted with 

 acidic alcohol (pH 2.0). Further purified by double 

 decomposition between sodium p-(p'-hydroxy- 

 phenylazo)benzene sulfonate and a crude salt of 

 the antibiotic, and other salt interconversions (8). 



Chemical ami physical properties: Complex, 

 containing three components (1). Base: m.p. about 

 195°C (decomposition). No characteristic absorp- 

 tion in ultraviolet light, [a]'-^ = +64° (c = 1 per 

 cent in water). Stable to autoclaving for 30 min- 

 utes at pH 8.4 and for 8 hours at 25°C at pH 2 to 

 10. C = 46.6%; H = 7.3%; N = 12.8%; O = 33.1%; 

 Van Slyke N = 11.35% (as nitrogen); acetyl in- 

 dex = 17.7%. C2:iH44N,;Oi:j . All hydroxyl groups 

 are reported to be in the form of secondary alco- 

 hols. Rf = 0.22 (water-saturated n-butanol-2 per 

 cent p-toluenesulfonic acid, Whatman No. 4 paper, 

 15 hours at 24°C (1, 8)). Hydrochloride: Amorphous 

 white powder. Soluble in water and aciueous 

 methanol. Insoluble in acetone, ether, and other 

 common organic solvents. [«]„ = +57° (c = 1 per 

 cent in water). Green color with the anthrone test. 

 Negative Elson -Morgan and Sakaguchi tests. All 

 N present is in the form of primary amino groups. 



Acid liydrolysis or methanolysis products include 

 neamine, a diamine hexose (C6H12O3N2 or CeH^- 

 O4N2), and a pentose. The amino sugar gives posi- 

 tive ninhydrin, Elson-Morgan, and ammoniacal 

 AgNOs tests, but a negative Keller-Kiliani (tor 

 desoxy-2-hexoses) test. Rf = 0.17 (n-butanol- 

 acetic acid-water, 50:25:25). The dipicrate ot this 

 amino sugar has a m.p. of 126 °C. Pentose gives 

 positive Tollen and Seliwanoff tests, reduces 

 l)enzidene and tetrazolium, and gives a negative 

 Keller-Kiliani test (3, 6, 10). Picrate: m.p. 189°C 

 (decomposition, corrected). [0]^ = —34° (c = 0.5 

 per cent in methanol (1). Sulfate: Soluble in water. 

 Insoluble in methanol, acetone, and ethyl ether. 

 [a]u = +44"^ (c = 1 per cent in water) (8). p-ip'- 

 H yd rox yphen ylazo)benzene sulfonate: Crystals; 

 m.p. 250°C. Soluble in methanol. Scarcely soluble 

 in ethanol. Insoluble in water, l)utanol, acetone, 

 ether, and ])enzene (8). 



Biological activity: Active on gram-positive and 

 gram-negative bacteria, including mycobacteria, 

 Proteus, and Pseudomonas spp. No cross-resistance 

 with streptomycin (5, 9, 11). Active in mice on 

 Staph, aureus, E. coli, Sal. typhosa, Sal. typkimur- 

 ium, Sal. paratyphi (A and B), D. pneumoniae, M. 

 tuberculosis var. hominis H37Rv, and B. anthracis 

 (8). 



Toxicity: LDao (mice) 40 to 50 mg per kg intra- 

 venously, 250 to 275 mg per kg intraperitoneally, 

 450 mg per kg subcutaneously, and >5 gm per kg 

 orally. LDf,,) (rat) 450 mg per kg intramuscularly, 

 700 mg per kg subcutaneously (8). Toxic to the 

 eighth cranial nerve (7). Chronic toxicity tests 

 showed that isonicotinic acid administered to 

 guinea pigs with framycetin overcomes the toxic- 

 ity of the antibiotic at certain levels (4). 



Utilization: Bowel sterilization (12). Pulmonary 

 disease (7). 



References : 



1. Hagemann, (1. T. Thesis, University of 



Paris, 1952. 



2. Decaris, L. J. Ann. pharm. franc. II: 



44-46, 1953. 



3. Pen^u, H. et al. Ann. pharm. franc. 11: 



431-438, 1953. 



4. Lutz, A. Compt.rend. 236:157-159,1953. 



5. IaxXz. \. et al. Strasbourg med. 4:431-433, 



1953. 



6. Janot, .M. M. et al. Bull. soc. chim. France 



21: 1458-1463, 1954. 



7. Sors, C. and Trocme, Y. Presse med. 61: 



364-365, 1954. 



8. Rendu, H. et al. French Patent 1,051,202, 



January 14, 1954. 



9. Lutz, A. and Witz, Al. A. Compt. rend. 



soc. biol. \W: 1467-1470, 1955. 



