222 



DESCRIPTIONS OF ANTIBIOTICS 



3. Berger, J. and Goldberg, M. W. J. Clin. 



Invest. 28: 1046, 1949. 



4. JampoLsky, L. M. and Goldberg, M. W. J. 



Clin. Invest. 28: 1046, 1949. 



5. Cooperman, J. M. et. al. Proc. See. Exptl. 



Biol. Med. 76: 18-20, 1951. 



6. Sugiura, K. and Sugiura, M. M. Cancer 



Research 18: (Suppl. 1) 290, 1958. 



Bottroniycin 



Produced by: Streptomyces bottropensis (1). 



Synonym: B-Mycin (1). 



Method of extraction: Broth-filtrate extracted 

 with butyl acetate. Extract concentrated azeo- 

 tropically. Concentrate washed with NaHCO? 

 solution and water, then extracted with phosphate 

 buffer (pH 2). Aqueous extract washed with ether 

 to remove butyl acetate; residual ether evaporated 

 and crude Ijottromycin precipitated by adjusting 

 to pH 9. Purification by chromatography on Flori- 



Positive bromine test. Rf = 0.94 on paper chro- 

 matography (water-saturated butanol with 2.5 

 per cent acetic acid). Salicylate: White crystals; 

 m.p. 160-161 °C. Acetate: Amorphous; m.p. 138- 

 148°C (decomposition). Poorly soluble in water. 



Hydrochloride: Cream-colored amorphous sub- 

 stance; m.p. 190-210°C (decomposition). Poorly 

 soluble in water. Acid hydrolysis products include 

 seven ninhydrin-positive substances, including 

 glycine, valine, and two unidentified crystalline 

 amino acids: (I) CioHuNO. (m.p. 176-177°C) and 

 (II) CeHgNaO.S (m.p. 197.5-201 .5°C). Degrada- 

 tion with boiling acetic anhydride yields two crys- 

 talline acetyl products: (III) C21H34N4O4 (m.p. 

 165-170°C) and (IV) C19H23N3O4S. Compound IV 

 is the methyl ester of an N-acetyl dipeptide com- 

 posed of I and II. I and II were identified as a- 

 amino-/3-phenylbutyric acid and |8-(2-thiazole)-/3- 

 alanine, respectively (3, 4). The structure of IV 

 is: 



-CH(CH3)— CH^CONH— CH— CHo— COOCH3 

 "^ / NH C. 



I a 



c=o 



s 



N 



CH3 



sil with chloroform as solvent and developer, or 

 by means of precipitates formed with organic 

 acids such as salicylic, benzoic, acetic, picric, or 

 anthranilic acids (2). Can also be adsorbed on 

 carbon and eluted with acetone-HCl; on IRC-120 

 and eluted with 10 per cent NaCl; on Magnesol 

 and eluted with benzene-methanol; or on Florisil 

 and fractionally eluted with chloroform containing 

 7.5 per cent ethanol. Active fractions acidified with 

 0.1 A' H2SO4 , and organic solvent removed in 

 vacuo. Precipitated from aqueous residue by ad- 

 justing pH to 9 (1). 



Chemical and physical properties: Weak sulfur- 

 containing base. Glittering, white amorphous 

 powder; m.p. 143-147°C (decomposition). CssHjg- 

 NtOsS: C = 58.94%; H = 7.78%; N = 12.53%,; 

 S = 3.88%. Molecular weight, about 770. pKa' = 

 about 6.5. Readily soluble in most organic solvents. 

 Insoluble in hexane, cyclohexane, and petroleum 

 ether. More soluble in ice water than water at 

 30°C. [a]f = -14.2° (c = 0.5 per cent in 96 per cent 

 ethanol). Ultraviolet absorption spectrum maxi- 

 mum at 203 ni/i and a weak shoulder at 240 m/j. 

 (1, 2). Infrared data given in reference 2. Less 

 stable at alkaline than acid pH (2). Negative nin- 

 hydrin test. One primary amino group (Van 

 iSlyke). No acetyl or N-alkyl groups. Two to 

 three C-methyl groups and one methoxyl group. 



Bottroniycin contains this methyl ester grouping 

 and is biologically inactivated on its removal (5) . 



Biological activity: Active on gram-positive bac- 

 teria and mycobacteria. Not active on gram-nega- 

 tive bacteria, except for Hemophilus, Neisseria, 

 and Brucella. No cross-resistance with carbomycin 

 or erythromycin. 



References: 



1. British Patent 762,736, December 5, 1956. 



2. Waisvisz, J. M. et al. J. Am. Chem. Soc. 



79: 4520-4521, 1957. 



3. Waisvisz, J. M. e/ a?. J. Am. Chem. 8oc. 79: 



4522-4524, 1957. 



4. Waisvisz, J. M. et al. J. Am. Chem. Soc. 



79: 4524-4527, 1957. 



5. Waisvisz, J. M. and Van der Hoeven, M. G. 



J. Am. Chem. Soc. 80: 383-385, 1958. 



Boviiiocidiii 



Produced- by: Streptomyces sp. 



Synonym: /3-Nitropropionic acid. 



Remarks: This comjiound had been isolated pre- 

 viously from plants and fungi. 



Method of extraction: Broth-filtrate adjusted to 

 pH 2.5 and extracted with ethyl acetate. Back- 

 extraction into pH 9.0 water. After adjustment of 

 pH to 2.5, extraction with ethyl acetate. Ethyl 

 acetate washed with water and evaporated to dry- 



