246 



DESCRIPTIONS OF ANTIBIOTICS 



extract passed through Florisil cohimu.s to remove 

 most dark-colored impurities. While l)eing 

 shielded from bright daylight to prevent further 

 pigment formation, the columns are washed with 

 the same solvent to remove the active material. 

 Bright yellow eluate concentrated in vacuo, and 

 recrystallized by dissolving in hot pyridine and 

 adding ethanol or by dissolving in hot acetic acid 

 and adding water. 



Chemical and physical properties: Slender green- 

 ish yellow needles or rods; m.p. 255-2(iO°C (decom- 

 position). Can be sublimed at 240°C without loss 

 of activity. Neutral substance, practically insol- 

 uble in water and petroleum ether; slightly soluble 

 in methanol, higher alcohols, and ethyl acetate; 

 and more soluble in pyridine, glacial acetic acid, 

 and dio.xane. Soluble in concentrated HCl and can 

 be recovered unchanged from it by adding water. 

 Dry crystals are photosensitive, and turn brown 

 on exposure to light. Stable from pH 3 to 7 and to 

 heating to 100°C. [a]^ = +16° (c = 1 per cent in 

 acetic acid). Ultraviolet maxima at 247 to 287 m^u 

 and a broad band between 390 to 400 m/x. Gives 

 inactive red solution in alkali. On hydrogenation 

 with platinum oxide as catalyst and glacial acetic 

 acid as solvent, 4 moles of hydrogen are taken up. 

 The colorless product, recrystallized from hot 

 ethanol, is devoid of biological activity and melts 

 at 208°C; ultraviolet maxima at 240 and 355 m/i. 

 Analysis of this hydrogenation product gave a 

 formula of C22H28O7 . Molecular weight 360. C = 

 65.46%; H = 6.96%; O = 27.47%,. From this anal- 

 ysis the tentative formula C22H20O7 is proposed 

 for chrysomycin, since the original compound 

 could not be analyzed satisfactorily. 



Biological activity: Active against B. cereus 

 phage at 0.01 Mg per ml, and other phages, includ- 

 ing staphylophage, streptophage, enterococci 

 phage, and cholera phage at 0.2 mg per ml by the 

 paper-disc method. Phagocidal to five bacterial 

 viruses. Has antibacterial activity (active mainly 

 against gram-positive bacteria) and slight anti- 

 fungal activity. 



Toxicity: Mice (20 gm) tolerate 2 mg in peanut 

 oil intraperitoneally; 5 mg by the same route pro- 

 duces transient paralysis and loss of appetite. 



Reference: 1. Strelitz, F. et al. J. Bacteriol. 

 69: 280-283, 1955. 



Ciniianiycin 



Produced by: Streptoniyces cinnanwnieiis (1) f. 

 cinnamonieus (4). 



Method of extraction: Broth-filtrate passed 

 through a column of IRC-50 (H+) and eluted with 

 0.1 N HCl. Neutralized to pH 6.0 with IR-4B. 



Effluent concentrated in vacuo and freeze dried. 

 Solid dissolved in 80 per cent methanol (acpieous) 

 and chromatographed on alumina. Development 

 with aqueous methanol (1). Countercurrent dis- 

 tribution (n-butyl alcohol and a volatile ammo- 

 nium acetate buffer, 0.2 M, pH 5.4) indicates the 

 presence of two substances, one of which is unre- 

 lated to cinnamycin (2). 



Chemical and physical properties: Cream-colored 

 powder. Basic polypeptide. Soluble in water, hy- 

 drated alcohols, and glacial acetic acid. Insolu- 

 ble in ether (1). Ultraviolet absorption spectrum 

 shows end-absorption at 230 m^t- Infrared spec- 

 trum given in reference 2. Acjueous solutions are 

 levorotatory. Stable at pH 2 to 9 for 30 minutes 

 at 92°C. Photo-stable. Not inactivated by pepsin 

 or trypsin (1). Dialyzes through cellophane. Iso- 

 electric point pH 5.0 (2). Contains N and S; no 

 halogen. Positive Sakaguchi and biuret tests. 

 Negative ninhydrin, FeCls , Molisch, maltol, Tol- 

 len, and reducing sugar tests. No sulfhydryl or 

 disulfide groups (1). Acidic and basic hydrolysis 

 products include aspartic acid, arginine, glutamic 

 acid, proline, phenylalanine, valine, mesolanthio- 

 nine, and /3-methyl lanthionine (C7H14N2O2S), 

 which has also been isolated from subtilin and 

 nisin (1, 2). 



Biological activity: Active on gram-positive rods 

 and mycobacteria (5 to 55 fxg per ml) ; very active 

 on Clostridium botulinuni (0.085 Mg per ml); not 

 active on gram-positive cocci, gram-negative bac- 

 teria, or yeasts (1). Tested against phytopatho- 

 gens and compared with duramycin (4). 



Toxicity: LDso (mice) 5 to 10 mg per kg intra- 

 peritoneally; 400 mg per kg or less is nontoxic 

 subcutaneously (3). 



References: 



1. Benedict, R. G. et al. Antibiotics & Chemo- 



therapy 2: 591-594, 1952. 



2. Dvonch, W. et al. Antibiotics & Chemo- 



therapy 4: 1135-1142, 1954. 



3. Ambrose, A. M. Antibiotics & Chemother 



apy 4: 1242-1244, 1954. 



4. Lindenfelser, L. A. et al . Antibiotics & 



Chemotherapy 9: 690-695, 1959. 



Cladomyciii 



Produced by: Streptomyces lilacinus (2). 



Method of extraction: Broth extracted with ethyl 

 acetate. Extract concentrated in vacuo at <40°C. 

 Precipitated from concentrate on addition of pe- 

 troleum ether. Taken up in ethyl acetate, washed 

 with HCl (pH 2.0) and NaOH (pH 10.0) solutions, 

 concentrated in vacuo at <40°C, and precipitated 

 as before. Purified by chromatography on a cellu- 



