DESCRIPTIONS OF ANTIBIOTICS 



255 



Synont/Ni.s of 7-chloro-G-demethly tetracycline: 

 Deinethylchlortetracycline, decloinycin, leder- 

 inycin. 



Chemical and physical properties: I. 6-De- 

 methyltetracycline hydrochloride hemihydrate : 

 m.p. 203-209°C (decomposition). C21H24N2CIO8.5 : 

 C = 52.52%; H = 5.34%; N = 6.05%; CI = 7.51%; 

 H2O = l.m%. [a]f = -259° (c = 0.5 per cent in 

 0.1 jV H2SO4). Ultraviolet absorption spectrum 

 maxima essentially the same as the corresponding 

 (i-methylated tetracycline (1). II. 7-Chloro-6- 

 demethyltetracycline sesquihydrate : m.p. 174- 

 178°C (decomposition). C21H24N2CIO9.6 : C = 

 51.13%; H = 4.93%; N = 6.00%; CI = 7.39%; 

 H2O = 4.45%. [a]f = -258° (c = 0.5 per cent in 

 0.1 A^ H2SO4). Both I and II and their epimers 

 (synthetic) are considerably more resistant to 

 alkaline or acidic degradation than other tetra- 

 cj'clines. Ultraviolet absorption spectrum maxima 

 of II are essentially the same as corresponding 

 6-methvlated tetracyclines (1). Structural formu- 

 las(l): 



R H OH H H H N(CH3)2 



OH I 

 OH O 



I: R = H 

 II: R = CI 



Biulogical activity: I and II: 24 and 75 per cent, 

 respectively, of the activit}- of chlortetracycline 

 against Staph, anrens. II is also active against 

 Staphylococcus, Streptococcus, Klebsiella, and 

 pneumococcal infections in mice (2). 



Toxicity: II has a low order of toxicity. Ab- 

 sorbed slowly from the gastrointestinal tract. 

 Produces very high serum concentrations, prob- 

 ably because it is cleared slowly by the kidney (1). 



Utilization: P^ffective in the treatment of a 

 number of himian diseases (3). 



References : 



1. McCormick, J. R. D. et at. J. Am. Chem. 



Soc. 79: 4561-4564, 1957. 



2. Sweeney, W. M. et al. Antibiotics <fc Chemo- 



therapy 9: 13-22, 1959. 



3. Finland, M. et al . Antibiotics Ann. 375- 



446, 1959-1960. 



De.serloniycin 



Produced by: Streptomyces ftarofungiiii . This 

 strain also produces flavofungin. 



Method of extraction: Extracted with organic 

 solvents from broth and mycelium. 



Chemical and physical properties: Snow-white, 

 glittering hexagonal crystals; m.p. 189-190°C. 

 Low solubility in water, absolute alcohols, ether, 

 and acetone; higher solubility in aqueous alcohols. 

 Positive bromine, KMn04 , ninhydrin, and Kuhn- 

 Roth (C-methyl) tests. Very soluble in neutral 

 aqueous solution. C33H60-62O14N. Does not con- 

 tain N — Me or acetyl groups. Gives hydrogenated 

 and acetylated products. 



Biological activity: Active on gram -positive and 

 gram-negative liacteria (1 to 25 Mg per ml). Inhibits 

 leukemic and Ehrlich ascites carcinoma cells in 

 vitro. Cystostatic (10 yug per ml) and cytolytic (50 

 to 100 Mg per ml) on fibroblast, HeLa, and Crocker 

 sarcoma cells by tissue culture method. 



Toxicity: LD50 (mice) 1.35 mg per kg intrave- 

 nously, 2.6 mg per kg intraperitoneally, 5.3 mg per 

 kg subcutaneously, and 12 to 15 mg per kg orally. 



Reference: 1. Uri, J. el al. Nature, London 

 1«2: 401, 1958. 



D 



lazoinvcins 



Produced by: Streptomyces ambofaciens. 



Synonyms: Related to azaserine, DON, and 

 alazopeptin. 



Method of extraction: Concentration of the fil- 

 tered broth to 5 to 10 per cent of original volume; 

 10 volumes of methanol added and the filtrate 

 concentrated. The aqueous concentrate passed 

 through a Dowex 1 acetate column. The effluent 

 contains 6-diazo-5-o.xo-l-norleucine (DON). The 

 cohnnn is eluted with 1 per cent phosphate buffer 

 at pH 7.0. Two active fractions are eluted. Frac- 

 tion A chromatographed on Celite or silica gel and 

 eluted with the system phosphate buffer-n-buta- 

 nol-isopropanol. The active component, diazo- 

 mycin A, converted to its lithium salt and crys- 

 tallized. Fraction B, which still contains some 

 diazomycin A, is purified by countercurrent dis- 

 tribution between phenol and water. Two peaks 

 are observed. Both fractions chromatographed on 

 Dowex 1 acetate resin. One of the fractions is 

 homogenous: diazomycin C. The other fraction 

 can be split into two components, diazomycin A 

 and a new component, diazomycin B. 



Chemical and physical properties: Aliphatic 

 diazo compounds. Very labile at acidic pH values. 

 Most stable between pH 6.0 and 8.0. Light ab- 

 sorption spectrum maxima at 275 and 245 niju. 

 Extinction coefficients at 275 niyu: diazomycin A, 

 520; B, 550; C, 340; at 245 ni/.: A, 315; B, 340; C, 

 210. Ninhydrin reaction: A and C, light gray-blue; 

 B, intense blue. Solubility in methanol: A and C, 

 readily soluble; B, slightly soluble. Rf values (80 

 per cent isopropanol) : A, 0.6 to 0.7; B, 0.2 to 0.3; 



