DESCRIPTIONS OF ANTIBIOTICS 



273 



No toxic eft'ect on young tomato plants sprayed 

 with 415 ng of filipin per ml of 25 per cent methanol 

 (1,2). 

 References: 



1. Gottlieb, 1). et al. Plant Disease Reptr. 



39: 219, 1955. 



2. Ammann, A. et al . Phytopathology 45: 



559-563, 1955. 



3. Whitfield, G. B. et al. J. Am. Chem. Soc. 



77: 4799-4801, 1955. 



4. Wallen, V. R. and Bell, W. Plant Disease 



Reptr. 40: 129-132, 1956. 



5. Gattani, M. L. Plant Disease Reptr. 41: 



160-164, 1957. 



6. Ark, P. A. and Thompson, J. B. Plant 



Disease Reptr. 41: 452-454, 1957. 



7. Natti,J.J. Plant Disease Reptr. 41:780- 



788, 1957. 



8. British Patent 783,486, September 25, 1957. 



9. Field, J. B. et al. Cancer Research 18: 



(Suppl. 1) 492, 1958. 



10. Sloneker, J. H. Thesis, University of Illi- 



nois, 1958. 



11. Tingstad, J. E. and Garrett, E. R. J. Am. 



Pharm. Assoc, Sci. Ed. 49: 352-355, 1960. 



Flavacid 



Produced by: Streptoniyces sp. closely related to 

 »S. flavus. 



Method of extraction: The mycelium of the Strep- 

 tomyces washed with water, dried, and crushed 

 into powder. Extraction of mycelium with 1:1 

 mixture of butyl acetate-acetone, or with ethyl 

 acetate. These solvents removed from the my- 

 celium a toxic antibiotic (D-substance), which is 

 discarded. Mycelium extracted with methanol and 

 discarded. Methanol evaporated in vacuo, and 

 the solid residue extracted with butanol at pH 

 5.0. Butanol-extract washed with acidic water 

 (pH 2.0) and adjusted to pH 7.0. After concentra- 

 tion of butanol to a small volume, flavacid is pre- 

 cipitated out with saturated alkaline methanol. 

 Yield: 500 to 800 mg per 100 gm of dry mycelium. 



Chemical and physical properties: Hexaene (2): 

 Weak acid, active and unstable under acidic con- 

 ditions. Sodium salt: solul^le in methanol and 

 aciueous acetone and moderately soluble in water 

 and ethanol; slightly soluble in acetone and buta- 

 nol; insoluble in ether, ethyl acetate, chloroform, 

 and benzene. Indicator properties: green in acid 

 solutions, yellow at neutrality, red at alkaline 

 pH. Inactive at neutrality and at alkaline reac- 

 tion. Ninhydrin and FeCh reactions negative. 

 Ultraviolet absorption maxima at 335, 355, and 373 

 m;u (methanol); m.p. 102-105°C (1). A tetraene 



(peaks at 293, 306, and 324 ni/x (ethanol)) is also 

 present in .small cjuantities, as with endomycin. 

 The hexaene from flavacid was shown to differ from 

 that of endomycin. Not enough of the tetraene 

 was present for comparison with the endomycin 

 tetraene (2). 



Biological activity: Active //( vivo against gram- 

 positive bacteria (3 to 6 ng per ml); verj^ slight 

 activity against gram-negative bacteria. Active 

 against yeasts and filamentous fungi, including 

 Trichophyton and C. albicans. Inactivated by 

 human serum. Experimental systemic infections 

 of mice and guinea pigs with ('. albicans do not 

 respond to flavacid treatment. Oral administra- 

 tion of flavacid reduces the nvmil>er of C albicans 

 in the digestive tract. 



Toxicity: LDso (mice) 50 mg per kg intraperito- 

 neally. 



I'tilization: Some effect in the treatment of tri- 

 chophytosis in man, when applied topically. Ex- 

 cellent results obtained in the topical treatment 

 of Trichomonas vaginalis in human beings. 



References: 



1. Takahashi, J. J. Antibiotics (Japan) 6A: 



117-121, 1953. 



2. Vining, L. C. and Taber, W. A. Can. J. 



Chem. 37: 1461-1466, 1957. 



Flavensoniycin 



Produced by: Streptoniyces sp. resembling S. 

 tanashiensis (2). 



Synonym: Antibiotic 829 (1). 



Method of extraction: Broth-filtrate extracted 

 with benzene at pH 7.5 to 8.0. Extract concen- 

 trated in vacuo until precipitate appears. Precipi- 

 tate washed with petroleum ether and extracted 

 with acetone. Acetone concentrated and petro- 

 leum ether added to precipitate crude flavenso- 

 mycin. Purification by chromatography on alu- 

 mina from a benzene solution, washing with ethyl 

 acetate, ethanol-ethyl acetate, and elution with 

 methanol (2, 3). 



Chemical and physical properties: Pale yellow, 

 odorless tabular crystals; m.p. 152° ± 2°C. Solu- 

 ble in water, lower alcohols and acetates, benzene, 

 chloroform, pyridine, acetone, dioxane, and pro- 

 pylene glycol. Insoluble in ether, petroleum ether, 

 hexane, carbon tetrachloride, and carbon disul- 

 fide. Contains N, but no S or halogen. Ultraviolet 

 absorption spectrum maximum at 251 niyu (metha- 

 nol). Infrared data given in reference 2. Stable, in 

 dry form, in organic solvents and in neutral 

 atiueous solutions at <12°C. Positive Molisch, 

 Fehling, and Ehrlich (diazo) tests. Negative Tol- 



