DESCRIPTIONS OF ANTIBIOTICS 



399 



U. Hosoya, S. et al. J. Antibiotics (Japan) 



8A: 5-8, 1955. 

 15. Hosoya, S. et al. J. Antibiotics (Japan) 



8A: 48-50, 1955. 

 IG. Ito, T. et al. J. Antibiotics (Japan) 8A: 



103, 1955. 



17. Hattori, K. et al. J. Antibiotics (Japan) 



8A: 137, 1955. 



18. Hattori, K. et al. J. Antibiotics (Japan) 



8B: 312-315, 1955. 



19. Hosova, S. and Hamamura, N. J. Anti- 



biotics (Japan) 8B: 417-418, 1955. 



20. Hosoya, S. et al. Chemotherapy 3: 10-15, 



1955. 



21. Hosoya, S. et al. Chemotherapy 3: 215- 



223, 1955. 



22. Hoso.va, S. and Hamamura, N. J. Anti- 



biotics (Japan) 9A: 129-131, 195(3. 



23. Nakano, H. et al. J. Antibiotics (Japan) 



9A: 172-175, 195(5. 



24. Hattori, K. et al. J. Antibiotics (Japan) 



9A: 176-181, 1956. 



25. Fujino, T. et al. Med. J. Osaka Univ. 8: 



579-584, 1958. 



Tubercidin 



Produced by: Streptomyces sp. 



Method of extraction: Broth-filtrate treated with 

 charcoal at pH 8.0. Elution with 80 per cent acidic 

 aqueous acetone. Acetone evaporated in vacuo. 

 Aqueous residue washed with butanol, adjusted 

 to pH 8, and extracted with butanol. Extract 

 concentrated in vacuo, then cooled to precipitate 

 tubercidin. Crystallized from boiling water. 



Chemical and physical properties: Basic sub- 

 stance; m.p. 247-248°C (decomposition). Insoluble 

 in acetone, ethyl acetate, chloroform, benzene, 

 and petroleum ether. Sparingly soluble in water, 

 methanol, and ethanol. Very soluble in water 

 above pH 10 or below pH 4. Stable at pH 2 to 10 

 when boiled for 5 hours. CUH14N4O4 : C = 49.76%; 

 H = 5.31%; N = 21.21%. Picrate: m.p. 229-231°C 

 (decomposition). pKa = 5.2 to 5.3 (10°C). Ultra- 

 violet absorption spectrum maxima at 227 and 270 

 myu in acidic solution, and at 270 ni/i in neutral or 

 alkaline solution. Infrared spectrum given in 

 reference 1. Positive diazo, Nessler, benzol, Bial 

 (pentose), and Wheeler-Tollen (pentose) tests. 

 Negative FeCls , Liebermann, Denige (tertiary 

 alcohol), Fehling, ToUen, and sodium nitroprus- 

 side tests. Negative Molisch test becomes positive 

 on acid hydrolysis. 4-Amino-7-(D-ribofuranosyl)- 

 pyrrolo-(2,3-d)-pyrimidine (2, 3). 



Biological activity: Active on mycobacteria, but 

 not on other bacteria. Verv slight activity on C. 



albicans. Active in vitro on NF mouse sarcoma, 

 but not on Ehrlich ascites carcinoma in vivo. 



Toxicity: LD50 (mice) about 45 mg per kg intra- 

 venously. 



References: 



\. \nzai,K.et al. J. Antibiotics (Japan) lOA: 

 201-204, 1957. 



2. Suzuki, S. and Marumo, S. J. Antibiotics 



(Japan) 13A: 360, 1960. 



3. Suzuki, S. and Marumo, S. J. Antiobitics 



(Japan) 14A: 34-38, 1961. 



Tubermycins 



Produced by: Streptomyces misakiensis. 



Method of extraction: Broth-filtrate extracted 

 with ethyl acetate at pH 2.4. Re-extracted into 

 0.2 A^ NaOH. Aqueous extract adjusted to pH 2.4 

 and extracted with ether. Extract concentrated 

 to dryness in vacuo. Crude residue taken up in 

 acetone and chromatographed on alumina (80 per 

 cent aqueous acetone as developer) to separate 

 tubermycins A and B. Crystallized from aqueous 

 acetone. 



Chemical and physical properties: Tubermycin 

 A: Monobasic acid. Long, fine, yellow needles; 

 m.p. 174°C. Ultraviolet absorption spectrum max- 

 ima (methanol) at 256 {EVL 3510) and 365 rati 

 (.Elem 570), which shift to 254 and 370 mp in acidic 

 methanol. Infrared spectrum given in reference 1. 

 Equivalent weight, 282. pKa = 7.6. One C— CH3 

 group. CnHieNoO.^ : C = 72.9%; H = 5.38%:; N = 

 9.9%,. Probably an alkyl-substituted phenazine 

 with a carboxyl function. Tubermycin B: Phen- 

 azine-a-carboxylic acid. Yellow needles; m.p. 

 243°C. Ultraviolet absorption spectrum maxima 

 (methanol) at 251 (Eum 3790) and 364 m^ (£'lcm 

 600) , shifting to 249 m// and 367 mn in acidic meth- 

 anol, but unchanged in alkaline methanol. Infra- 

 red spectrum given in reference 1. C13H8N2O2 : 

 C = 69.51%; H = 3.5%,; N = 12.29%; no C-CH3 

 group. Equivalent weight, 230. pKa = 7.0. Both A 

 and B are very soluble in alkaline water and sul- 

 furic acid (red solution). Moderately soluble in 

 acetone, acetic acid, dioxane, and dimethylforma- 

 mide. Sparingly soluble in methanol, ethanol, ethyl 

 acetate, benzene, and ether. Hardly soluble in 

 water. Positive hydroxamic acid test. Negative 

 Fehling, FeCls , maltol, ninhydrin, and diazo 

 reactions. 



Biological activity: Tubermycin A: Active on 

 mycobacteria at 1.25 to 20 fxg per ml. Tubermycin 

 B: Active on mycobacteria at 10 to 50 ^g per ml. 

 Inactive against bacteria and fungi. Serum de- 

 presses activity somewhat. 



