DESCRIPTIONS OF ANTIBIOTICS 



277 



10. Saito, A. and Schaffiier, C. P. Resvunes 3rd 



Intern. Congr. Biocheni. 98, 1955. 



11. Lutz, A. and Hofferer, M. J. Rev. imnmnol. 



19: 68-85, 1955. 



12. Shidlovsky, B. A. el al. Antibiotics Ann. 



118-121, 1955-1956. 



13. Waksman, S. A. Neomycin. The Wil- 



liams & Wilkins Co., Baltimore, 1958. 



14. Rinehart, K. L., Jr. ct al. .). Am. Chem. 



Soc. 82: 3938-3946, 19C.(). 



Fungicliroiiiiii 



Produced bi/: Streptonujces cellulosne (1). This 

 strain also ])roduces an actinomycin. 



Sniiini i/ni: l''ungichromatin , a closely related 

 compound ( 1 ). 



Method of extraction: Ivxtracted from l>roth- 

 filtrate with ethyl or amyl acetate, or other organic 

 solvents, and from mycelium with methanol, 

 ethanol, or acetone. Extracts concentrated /// 

 rocuo to precipitate a fungichromin-actinomycin 

 mixture. Separated by repeated crystallization 

 from methanol. 



Chemical and phi/sical properties: Conjugated 

 pentaene (3). Pale yellow crystals; m.p. 205-210°C 

 (uncorrected). Soluble in methanol, ethanol, 

 butanol, acetone, pyridine, and dimethylformam- 

 ide. Insoluble in water and aliphatic hydro- 

 carbons. Ultraviolet absorption spectrum maxima 

 at 322.5, 338.5, and 356.5 m/x, with a shoulder at 

 310 niyu (in organic solvents). Infrared data given 

 in reference 1. Violet color, changing to blue in 

 concentrated sulfuric acid. Positive ToUen (slow), 

 KMn04 , and bromine tests. Hydrogenation prod- 

 uct is a white, waxy solid, with no antifungal 

 activity. Mild acetylating conditions destroy 

 antibiotic activity but not characteristic ultra- 

 violet absorption. C = 60.93%; H = 8.65%; O = 

 30.42%. Molecular weight, 688.8. C,;,Hf,„0,., . Con- 

 tains 10 toll hydroxyl groups, and 3 to 4 C — CHs 

 groups, but no methoxyl or acetoxyl groups, N, S, 

 or halogens. Sodivmi periodate oxidation yields, 

 among other products, 2-methyl-2,4,6,8,10- 

 dodecapentaenedial (1, 3). 



Biological activity: Active on yeasts and fungi: 

 C albicans, 6.25 to 12.5 ^g per ml; Blastomyces 

 ilermatitidis, 0.78 /xg per ml ; A. niger, 3 to 25 ng per 

 ml; Trichophyton mentagrophytes, 12.4 to 50 /ig per 

 ml; Fusariiun oxysporum, 10 jug per ml. Active on 

 l^each brown rot (Sclerotinia fructicola) (1,2). 



Toxicity: LD.^r, (mice) 16.4 mg jjer kg intra- 

 peritoneally. Mice tolerate 1000 mg jjer kg orally 

 (1). 



References: 



1. Tytell, A. A. et al. Antiljiotics Ann 

 718, 1954-1955. 



■16- 



2. Szkolnik, M. and Hamilton, J. M. Plant 



Disease Reptr. 41 : 289-292, 1957. 



3. Cope, A. C. and Johnson, H. E. J. Am. 



Chem. Soc. «(»: 1504-1506, 1958. 



Fiisconiyeiii 



Produced by: Streptoniyces fuscus. 



Synoriy)ns: Related to flaveolin. Differentiated 

 from luteomycin and xanthomycin (1). 



Method of extraction: Adsorbed from l)roth on 

 carbon or cation exchange resin. I'^luted with 

 acidified acetone, methanol, or ethanol. 



Chemical and physical properties: Basic sulj- 

 stance. H ydrochloride: Decomposes at 180°C. 

 Soluble in methanol, ethanol, butanol, and ace- 

 tone. Insoluble in ether, ethjd acetate, l)utyl 

 acetate, lienzene, petroleum ether, chloroform, 

 and carbon tetrachloride. Negative Sakaguchi, 

 Molisch, Benedict, glucosamine, maltol, Fehling, 

 FeChi , and ninhydrin tests. End-absori)tion of 

 ultraviolet light . 



Biological activity: Active on gram-positive 

 bacteria; less active on gram-negative bacteria. 

 Cross-resistance with streptomycin and strep- 

 tothricin. 



Toxicity: Mice tolerate injections (no route 

 given) of 500 mg per kg. 



References: 



1. Ishida, N. and Miyazaki, J. J. Autilnotics 



(Japan) 5:481-487,1952. 



2. Hata, T. Japane.se Patent 5046, 1953. 



Ganciditis 



Produced by: Streptoniyces sp. 



Method of extrac'idu : Filtered Ijroth treated with 

 activated carbon. i",lu1 ion with 50 per cent acetone 

 (pH 2.0). Eluate adjusted to pH 6.0, filtered, con- 

 centrated in vacuo, and filtered again. Evaporated 

 to dryness in vacuo and residue taken up in a small 

 volume of methanol. Addition of ether precipi- 

 tates crude gancidin. The antibiotic could also be 

 extracted with organic solvents at acid pH and re- 

 extracted into water at alkaline i)H. Purified and 

 fractionated by count ere vu-rent distril)ution 

 (chloroform-McIlvaine's Iniffer). With the buffer 

 at pH 4.25, three biologically active fractions are 

 obtained, I, II, and III. Fraction II is concen- 

 trated and redistril)uted countercurrently in the 

 above system. The major active fraction is taken 

 to dryness. An ether solution of the residue is con- 

 centrated to give gancidin A crystals. Fraction I 

 is redistributed countercurrently in the above 

 system with the buffer at pH 2.5. The fraction in 

 the first four tul)es is concentrated and ether added 

 to give gancidin W. (Jancidin W recrystallized 

 from chloroform. Fraction III contains two com- 

 ponents (1, 2). 



