DESCRIPTIONS OF ANTIBIOTICS 



257 



G. Rake, G. et al. Am. Rev. Tuhere. 58: 

 479-480, 1948. 



7. Edison, A. O. et al. Am. Rev. Tuhere. 58: 



487-493, 1948. 



8. Hobson, L. B. et al. Am. Rev. Tuhere. 58: 



501-524, 1948. 



9. Wak.sman, S. A., ed. Streptomycin; nature 



and practical applications. The Williams 

 & Wilkins Co., Baltimore, 1949. 



10. Solomons, J. A. and Regna, P. P. Science 



109: 515, 1949. 



11. Wolf, E. J. et al. Science 1(19: 515-516, 



1949. 



12. O'Connor, J. B. ct al. Am. Rev. Tuhere. 



63: 312-324, 1951. 



13. Williamson, M. et al. J. Biol. C'hem. 197: 



7G3-770, 1952. 



14. Wolf, F. J. U. S. Patent 2,594,245, April 



22, 1952. 



15. Bogert, V. V. and Solomons, I. A. J. Am. 



Chem. Soc. 75: 2355-2351), 1953. 



16. Reitman, M. and Iverson, W. P. Anti- 



biotics Ann. 604-608, 1953-1954. 



17. Janke, A. and (iranits, J. Zentr. Bakteriol., 



Parasitenk., Abt. 2 108: ()(i-75, 1954. 



18. Signol, M. Compt. rend. soc. l)iol. 148: 



64(5-648, 1954. 



19. Foye, W. D. c/ a/. J. Am. Pharm. Assoc, 



Sci. Ed. 44:261-263,1955. 



20. Huebner, R. A. et al. Cornell Vet. 46: 



219-222, 1956. 



21. Katz, L. U. S. Patent 2,744,892, May 8, 



1956. 



22. Keller, H. et al. Arzneimittel-Forsch. 6: 



61-66, 1956. 



23. Belgian Patent 553,388, Decemlier 13, 1956. 



24. Keller, H. et al. Antibiotics Atui. 549-553, 



1956-1957. 



25. Hawkins, J. E., Jr. et al . Antil)iotics Ann. 



554-5(>3, 1956-1957. 



26. Osterberg, A. C. et al. Antibiotics Ann. 



564-573, 1956-1957. 



27. Mihaly, J. P. et al. Antil)iotics Ann. (302- 



608, 1957-1958. 



28. Hewitt, W. L. et al. Antibiotics Ann. 



609-613, 1957-1958. 



29. (ientry, R. F. Avian Diseases 2: 7(i-82, 



1958. 



30. Brigham, R. S. and Nielsen, J. K. Anti- 



biotics & Chemotherapy 8: 122-129, 

 1958. 



31. Weinstein, L. and Ehrenkranz, N. J. Strep- 



tomycin and dihydrostreptomycin. Med- 

 ical p]ncyclopedia, Inc., New York, 1958. 



32. Kavanagh, F. Appl. Microl)i()l. 8: KiO- 



l(j2, 19()0. 



Dill y<lr«>(lesox_vs t rep toniyciii 



Froiliiced hi/: This antibiotic is a chemical de- 

 rivative of streptomycin. 



Chemical and physical properties: More stable 

 in solution than dihydrostreptomycin. Structural 

 formula given in Chapter 6. 



Biological activity: Equally as active as dihydro- 

 streptomycin in vitro against a variety of bac- 

 teria; equally active in vivo against M. tuberculo- 

 sis. .Slightly less effective against other infections. 



Toxicity: LD.m) (mice) 214 mg per kg (no route 

 given). This substance is reputed to be slightly 

 less toxic than dihydrostreptomycin. No vestibu- 

 lar or ototoxic symptoms were observed in hunum 

 beings treated with the drug. 



Utilization: Treatment of tuberculosis. 



Reference: 1. Obuchi, S. et al. J. Antibiotics 

 (Japan) IIA: 199-201, 1958. 



l,6-Dihy(lro.\ypliena/;iiie 



Produced by: Streptoniyces thioluteus. 



Remarks: 1 ,6-Dihydroxyphenazine is also ob- 

 tained by the reduction of iodinin, an antibiotic 

 jjroduced by Pseudomonas iodinuui. 



Methixt of e.rlrartion: Culture-filtrate extracted 

 with benzene at pll 6.5 to 7.0 or adjusted to pH 12, 

 filtered, and filtrate neutralized to give a precipi- 

 tate. Precipitate extracted with benzene. Benzene 

 extracted with 0.1 A^ NaOH, and extract neutral- 

 ized to give a yellow jjrecipitate. Precipitate re- 

 extracted with l)enzene. Benzene concentrated in 

 vacuo. Crystallized from dioxane or ethyl acetate 

 or piu'ified l)y svdilimation. 



Chemical and physical properties: Golden-yellow 

 prisms; ni.p. 274°C. Very soluble in dioxane and 

 pyridine. Soluble in alcohols, acetone, ethyl ace- 

 tate, chloroform, l)enzene, ethyl ether, aqueous 

 sodium carl)onate, and NaOH. Insoluble in water, 

 aqueous sodium bicarbonate, and petroleum ether. 

 Ultraviolet absorption spectrum maxima at 272 

 (^ie™ ()350), 372 (^J^ni 245), and 440 to 445 mfi 

 iE\%, 165) (methanol), or 291 (EI^'^, 4300) and 520 

 to 530 niM (£'i'rm 180) (0.1 N NaOH). Infrared ab- 

 sorption spectrum given in reference 1. Puri)le in 

 alkali. i<>thanol solution turns green with FeCls , 

 gives a blue precipitate with lead acetate. Gives a 

 green-blue precipitate with cupric sulfate and a 

 violet precipitate with silver nitrate. Ci'HsN-iOi : 

 C = 68.48%; H = 3.99%; N = 13.51%,. Structural 

 formula given in Chapter 6. Diacetyl derivative: 

 Light yellow needles; m.p. 235°C. 



Biological activity: Active at 3 to 20 jug per ml on 

 certain yeasts and fungi. Not active on bacteria. 



Reference: 1. Akabori, H. and Nakamura, M. 

 J. Antibiotics (Japan) 12A: 17-20, 1959. 



