230 



DESCRIPTIONS OF ANTIBIOTICS 



16. Riser, J. S. and deMello, G. C. Proc. 58th 



Ann. Meeting U. S. Livestock Sanitary 

 Assoc. 81-97, 1954. 



17. Bogacz, J. Bull. soc. pathol. e.xotique 47: 



903-913, 1954. 



18. Hawley, G. E. and Downing, H. E. Anti- 



biotics Ann. 336-340, 1954-1955. 



19. Reynolds, W. M. et al. Antibiotics Ann. 



510-515, 1954 1955. 



20. Hochstein, F. A. and Regna, P. P. J. Am. 



Chem. Soc. 77: 3353-3355, 1955. 



21. Nakazawa, K. et al. J. Agr. Chem. Soc. 



Japan 29: 661-664, 1955. 



22. British Patent 738,537, October 12, 1955. 



23. Jones, W. F. et al. Proc. Soc. Exjitl. Biol. 



Med. 93: 388-393, 1956. 



24. Tanner, F. W., Jr. et al. U. S. Patent 



2,771,392, November 20, 1956. 



25. Friedman, I. J. et al. U. S. Patent 2,792,330, 



May 14, 1957. 



26. Tanner, F. W., Jr. et al. U. S. Patent 



2,796,379, June 18, 1957. 



27. Nitta, K. Japan. J. Med. Sci. & Biol. 10: 



277-286, 1957. 



28. Woodward, R. B. Angew. Chem. 69:50-58, 



1957. 



29. Brink, N. G. and Harman, R. E. Quart. 



Revs. (London) 12: 93-115, 1958. 



30. Lawrence, J. C. Brit. J. Pharmacol. 14: 



168-173, 1959. 



31. Ryan, F. J. et al. J. Infectious Diseases 



78: 223-231, 1946. 



Carbomycin B 



Produced by: Streptotnyces halstedii. This culture 

 also produces carbomycin (1). 



Synonym: Magnamycin B. 



Method of extraction: Methanol-w^ater mother 

 liquors from carbomycin recrystallizations are 

 diluted with a large volume of water to give a 

 precipitate. Dried precipitate taken up in anhy- 

 drous ethanol and stirred at room temperature for 

 8 hours. Carbomycin, crystallized by this proce- 

 dure, filtered off. Filtrate evaporated, dissolved in 

 acetone, and water added to turbidity. Carbo- 

 mycin B separated out overnight. Recrj'stallized 

 from a 5:1 acetone-water mixture and anhydrous 

 acetone (1). 



Chemical and physical properties: Probably is an 

 Q:,|3,7,6-unsaturated ketone. Weakly basic sub- 

 stance. May be isomeric with carbomycin. Color- 

 less anisotropic plates, frequently hexagonal; 

 m.p. 140-144°C (decomposition); softens at 138°C. 

 Soluble at 20-25°C in methanol to 1.4 gm per ml; 

 ethanol 0.45 gm per ml; acetone 0.25 gni i)er ml; 



benzene 0.15 gm per ml; ether 0.03 gm per ml; and 

 water, 0.1 to 0.2 mg per ml (1, 3). Ultraviolet ab- 

 sorption spectrum maximum at 278 niju (J^lcm 276) 

 (E = 25,000). Infrared spectrum given in refer- 

 ence 1. [a]; = —35° (c = 1 per cent in chloroform). 

 Buffered aqueous solutions (pH 5.0) have a half- 

 life of >3 months. Less stable at pH 3 or 10. C = 

 60.55%; H = 8.42%; N = 1.78%; O— CHg = 4.01%; 

 N— CH3 = 3.10%o- Equivalent weight 870. pKb = 

 7.56. C4i.4.>H67-69NOi5-i6 . Hvdrolysis lu methanoUc 

 HCl yields, like carbomycin, methyl mycarose 

 isovalerate. Vigorous acid hydrolysis yields, again 

 like carbomycin, mycaminose. Other evidence in- 

 dicates that carbomycin B may differ from carbo- 

 mycin in more than one double position, and may 

 contain one oxygen atom less (1). Hydrochloride: 

 White crystals. More soluble in water than the 

 base, but less so than carbomvcin A hydrochloride 

 (2). 



Biological activity: Resembles carbomycin (1). 

 Stimulates rat growth without concomitant fecal 

 microflora changes, when administered intraperito- 

 neally, but has no growth-stimulatory effect and 

 produces marked changes in intestinal microflora 

 when given orally (2). 



Toxicity: LD50 (mice) 300 mg per kg intrave- 

 nously. Other routes are comparable to carbo- 

 mycin (1). 



References: 



1. Hochstein, F. A. and Murai, K. J. Am. 



Chem. Soc. 76: 5080-5083, 1954. 



2. Dick, E. C. and Johansson, K. R. Anti- 



biotics & Chemotherapy 7: 349-358, 1957. 



3. Tanner, F. W. et al. U. S. Patent 2,785,104, 



March 12, 1957. 



Carcinoniycin 



Produced by: Streptomyces carcinomycicus , 

 Streptomyces sp. (4), S. gannmycicus (2), and *S. 

 ganmycicus (3). 



Synonyms: Gannmycin; carzinomycin (4). 



Method of extraction: Precipitated from broth- 

 filtrate with 50 per cent ZnCh . Precipitate ex- 

 tracted with Na2HP04 at 25°C. Zn3(P04)2 filtered 

 off and supernatant dialyzed against running wa- 

 ter at 0°C for 48 hours. One per cent NaCl is added 

 and the antibiotic reprecipitated bj^ addition of 

 acetone. Precipitate taken up in water and freeze 

 dried. Cannot be extracted with organic solvents. 



Chemical and physical properties: Dark brown 

 powder. 



Biological activity: Active against Ehrlich carci- 

 noma (ascites form) in mice. No activity on bac- 

 teria or fungi. 



Toxicity: Mice tolera.te 500 mg per kg int raven- 



