310 



DESCRIPTIONS OF ANTIBIOTICS 



(2), but not on Fs. aeruginosa (4). Early reports of 

 activity against Mycobacteriiun tiiherciilasis H87Rv 

 in mice and hamsters (3) were not supported by 

 further work with highly purified preparations (6). 

 Isomycomyctn: Active on mycobacteria (10). 



Toxicity: Mice tolerate 25 mg per kg intrave- 

 nously (4, 8). Guinea pigs tolerate subcutaneously 

 administered mycomycin verj^ poorly, but 2.5 

 mg per day for 35 days is nontoxic (5). 



References: 



1. Johnson, E. A. and Bur don, K. L. J. Bac- 



teriol. 51: 281, 1947. 



2. Johnson, E. A. Bacteriol. Proc. 68-69, 



1949. 



3. Hobby, G. 8th Veterans Admin. Strepto- 



mycin Conf. 295-298, 1949. 



4. Jenkins, D. E. 9th Veterans Admin. Strep- 



tomycin Conf. 179-186, 1950. 



5. Jenkins, D. E. 10th Veterans Admin. Conf. 



Chemotherapy Tuberc. 286-287, 1951. 



6. Jenkins, D. E. 11th Veterans Admin. Conf . 



Chemotherapy Tuberc. 309-310, 1952. 



7. Celmer, W. D. and Solomons, I. A. J. Am. 



Chem. Soc. 74:1870-1871,1952. 



8. Celmer, W. D. and Solomons, I. A. J. Am. 



Chem. Soc. 74: 2245-2248, 1952. 



9. Celmer, W. D. and Solomons, LA. J. Am. 



Chem. Soc. 75: 1372-1376, 1953. 

 10. Celmer, W. 1). U. S. Patent 2,703,328, 

 March 1, 1955. 



Mycoiliotlin 



Produced by: Streptoniyces sp. 



Method of extraction: Extracted from broth- 

 filtrate with chloroform, methyl isobutyl ketone, 

 or n-butanol, at pH 4.0 to 8.0. The mycelium-filter- 

 aid cake is eluted with methanol to recover a 

 minor portion of active component. Concentration 

 of the chloroform-extract precipitates a white, 

 antibiotically inactive substance mixed with red 

 crystals of mycorhodin. Crystallization from 

 methanol or acetone gives the inactive substance 

 as a precipitate. Mycorhodin recovered from the 

 mother liquors on addition of petroleum ether. 

 Recrystallized from hot methanol with water or 

 warm chloroform-ether (1:1). Purified by chroma- 

 tography on Super-Cel from chloroform-ether, and 

 by countercurrent distribution in a methanol- 

 water-chloroform-carl)on tetrachloride (3:1:1.5:4) 

 system or methanol-methyl isobutyl ketone-water 

 (1:1:1). 



Chemical and physical properties: Indicator sub- 

 stance. Bright red needles; m.p. 200-202°C (de- 

 composition, corrected). Soluble in aqueous meth- 

 anol. Ultraviolet absorption spectrum maxima at 



258 niM iB^L 426), 420 m^ (^'IL 85), and 471 m^ 

 (filem 87) (95 per cent ethanol); or at 258 niju {E^i^^ 

 563), 410 m^x (^IL 79), and 461 m^ (E'lL 82) (95 

 per cent ethanol-0.1 .V HCl); or at 595 m^ (^'um 

 136) (95 per cent ethanol-0.1 A' NaOH). Infrared 

 spectrum data given in reference 1. In aqueous 

 methanol, red-orange color changes to purple at 

 pH 8.10, and to deep blue at higher pH values. 

 Dark red-purple color in concentrated H2SO4 and 

 alcoholic FeCla . Brown color in KMn()4 . De- 

 colorized by H2O2 at alkaline but not at neutral 

 pH. A solution of the antibiotic lost l)oth indicator 

 and antibiotic properties when kept for 12 hours 

 at room temperature, but was stable under these 

 conditions at 6°C. Very stable to acid. Contains 

 no amino acids. Hydrolysis products include re- 

 ducing sugars. C = 58.7%; H = 5.2%; N = 2.1%. 

 Molecular weight, 635 to 698. Acetyl derivative: 

 Yellow crystals. Inferior antibiotic activity. Di- 

 potassium salt: Amorphous, l)lue salt. Water- 

 soluble. Stable. 



Biological activity: Active on gram-positive 

 l)acteria and mycobacteria, but not on gram- 

 negative bacteria. Active in protecting and curing 

 mice with infections of D. pneumoniae and Staph, 

 aureus. 



Toxicity: LD50 (mice) 170 mg per kg intraperi- 

 toneally, about 500 mg per kg intramuscularly, 

 and >1250 mg per kg orally. Produces severe 

 delayed toxicity symptoms, including blood ab- 

 normalities, in dogs in chronic toxicity studies. 



Reference: 1. Misiek, M. et al. Antibiotics & 

 Chemotherapy 9: 280-285, 1959. 



Mycospocidin 



Produced by: Streptomyces bobiliae. 



Method of extraction: Broth extracted with liuta- 

 nol; mycelium with methanol-pyridine (3:1). 

 Methanol -pyridine evaporated and extracted with 

 l)utanol. Combined butanol-extracts washed with 

 water at pH 8.0 and pH 2.0, and then evaporated 

 to about 1^0 volume. Addition of acetone to con- 

 centrate precipitates crude mycospocidin. Purifi- 

 cation by chromatographing a pyridine solution 

 on alumina suspended in methanol -benzene, wash- 

 ing with methanol-benzene (1:1), and eluting 

 with methanol-pyridine (1:1). Further purifica- 

 tion by countercurrent distribution (ethyl acetate- 

 pyridine-water, 5:1:5). 



Chemical and physical properties: White crystal- 

 line powder; m.p. 233-234°C (decomposition). 

 [a]n = +56° (1.0 per cent in pyridine). Soluble in 

 pyridine and aqueous NaOH. Sparingly soluble 

 in methanol and ethanol. Insoluble in acetone, 

 ethyl acetate, benzene, chloroform, carbon tetra- 



