182 



DESCRIPTIONS OF ANTIBIOTICS 



extract neutralized to pH 7.0, concentrated in 

 vacuo, and freeze dried. Purification from a metha- 

 nol solution on alumina. Developed with metha- 

 nol and 90 per cent methanol. Further purifica- 

 tion by partition chromatography on Celite 545 

 with development with a lower phase of CC14-90 

 per cent aqueous phenol-water, 82:18:25. Peak 

 fractions are pooled, diluted with carbon tetra- 

 chloride, and extracted with water. Aqueous ex- 

 tract adjusted to pH 7.0 and extracted with ether. 

 Extract concentrated in vacuo and freeze dried. 

 Recrystallization from 95 per cent ethanol in the 

 cold, 90 per cent aqueous methanol, and 70 per 

 cent aqueous acetone (1). 



Chemical and physical properties: Ci6H2iN706- 

 H2O: C = 43.59%; H = 5.96%; N = 23.64% (Du- 

 mas); N (diazo) = 13.72%,; N (nondiazo) = 

 10.4%; H2O = 2.85%. No specific melting point. 

 Decomposes over a wide temperature range. 

 Very soluble in water; somewhat soluble in acetic 

 acid, formamide, dimethyl sulfoxide, and aque- 

 ous solutions of methanol, ethanol, and acetone. 

 Insoluble in absolute alcohols, acetone, ethyl 

 acetate, and ether. [a]f, = +9.5° (c = 4.7 per 

 cent in water). Stable at alkaline pH and neu- 

 trality, but not at acid pH. Ultraviolet absorp- 

 tion maxima (pH 7.0, phosphate buffer) at 242 

 niM (E]^m 321) and 274 mfx (El^ 549), typical of 

 aliphatic diazoketones. Infrared spectrum given 

 in reference 1 . Liberates nitrogen on acidification 

 with strong acids, with loss of biological activity 

 and ultraviolet absorption characteristics. Posi- 

 tive ninhydrin reaction. Positive biuret reaction 

 after acidification or treatment with l)romine 

 water. Untreated alazopeptin gives a yellow pre- 

 cipitate with the biuret reagents. Acid hydrolysis 

 products include a-alanine, representing 21.4 per 

 cent of the antibiotic. Oxidation with periodic 

 acid yields a peptide, which on acid hydrolysis 

 yields glutamic acid and a-alanine, indicating 

 that the antibiotic is a peptide containing a-ala- 

 nine and a Ce diazoketoamino acid (1). 



Biological activity: Slightly active in mice on 

 sarcoma 180 (ascitic and solid) and Ehrlich car- 

 cinoma (solid form) (4). 



Toxicity: LD50 (rat) 150 mg per kg intraperi- 

 toneally. Toxic to fetuses in utero at one thirtieth 

 of the adult LD50 (3). 



References: 



1. De Voe, S. E. et ul. Antibiotics Ann. 730- 



735, 1956-1957. 



2. Backus, E. J. et al. Antibiotics & Chemo- 



therapy 7: 532-541, 1957. 



3. Thiersch, J. B. Proc. Soc. Exptl. Biol. 



Med. 97: 888-889, 1958. 



4. Sugiura, K. Ann. N. Y. Acad. Sci. 76: 

 575-585, 1958. 



Albofiingiii 



Produced by: Strcptomyces alhus (2) or S. albiis 

 var. fungatus (3). 



Method of extraction: Mycelium washed with 

 acetone, then extracted with A^ HCl in acetone. 

 Extract neutralized with CaCOs ; precipitate 

 forms on dilution with water. Reprecipitated 

 from acidic acetone with petroleum ether. Chro- 

 matographed on alumina from acetone (2). 



Chemical and physical properties: Complex, con- 

 taining .several closely related components. Yel- 

 low powder. Decomposes without melting at 

 190°C. Soluble in chloroform, acetone, and di- 

 methylformamide. Less soluble in alcohols. In- 

 solul)le in water and ether. Ultraviolet absorption 

 spectrum maxima at 240, 255, 305, and 375 mn. 

 Contains C, H, O, and N (2). 



Biological activity: Active on yeasts, filamen- 

 tous fungi, gram-positive bacteria (1), and cer- 

 tain gram-negative bacteria (3). 



References: 



1. Caykovskaya, S. M. and Tyebyakina, A. E. 



Abstr. Communs. Symposium on Anti- 

 biotics. Prague, 1959, pp. 142-143. 



2. Chochlov, A. S. and Liberman. (1. S. Abstr. 



Communs. Symposium on Antibiotics. 

 Prague, 1959, pp. 154-155. 



3. Solovyeva, N. J. et al. Abstr. Communs. 



Symposium on Antibiotics. Prague, 1959, 

 pp. 189-191. 



A 1 bom y eel ill 



Produced by: Strcptomyces albiis (1) iind a Strcp- 

 tomyces sp. resembling S. albus (3). 



Method of extraction: I. Broth-filtrate ex- 

 tracted with ethyl acetate, benzene, chloroform, 

 or butanol at pH 8.0. Back-extracted into acidic 

 water (pH 1.0). The aciueous extract can be: (a) 

 concentrated and adjusted to alkaline pH to pre- 

 cipitate the antibiotic; or (b) extracted into ethyl 

 acetate at pH 8.0 and chromatographed on AI2O3 

 with ethyl acetate as developer. Colorless frac- 

 tion dried in vacuo, taken up in benzene, and 

 again dried in vacuo. Recrystallized from acetone- 

 ether (1:9) (1, 3). II. Adsorbed from broth-fil- 

 trate on a cation exchange resin or activated 

 charcoal. Eluted with 80 per cent acidic acetone. 

 Eluate concentrated in vacuo, then treated as in 

 1(b) (1, 3). 



Chemical and physical properties: Basic sub- 

 stance. Colorless hexagonal crystals; m.p. 166- 

 167°C (1) or l(i4-l()6°C (3). Soluble in xylene, 



