186 



DESCRIPTIONS OF ANTIBIOTICS 



Aniiccliii H 



Produced by: Streptornyces plicatus (2, 3). 



Synonyms: Plicacetin, believed to be a pre- 

 cursor of amicetin (1); antibiotic C (2). 



Method of extraction: Broth-filtrate extracted 

 with l-butanol at slightly alkaline pH values, 

 extract concentrated, then back-extracted into 

 water at pH 2.0. Could be precipitated from aque- 

 ous solutions with various aromatic azosulfonic 

 acid dj'es, or adsorbed on and eluted from IRC- 

 50. Precipitated from absolute methanol solution 

 with ether or by raising an aqueous solution to 

 pH 9.0 with NH4OH. Recrystallization from hot 

 water or dilute aciueous methanol gives crystal 

 form I; from ethyl acetate, crystal form II; and 

 from absolute ethanol, crystal form III (1). 



Chemical and physical properties: Crystal I: ni.p. 

 182-184 °C; colorless needles. Crystal II: m.p. 

 160-163°C; colorless needles. Crystal III: m.p. 

 222-225°C; dense prisms. Base: [a]'^ = +181° 

 (c = 2.7 per cent in methanol). Soluble in dilute 

 acid, lower alcohols, chloroform, and methylene 

 chloride. Sparingly solulale in ethyl acetate, ether, 

 and cold water. Insoluble in benzene and petro- 

 leum ether. Ultraviolet absorption spectrum 

 maxima: 257 and 311.5 m/x (0.1 N HCl), 249 and 

 321 niM (pH 7.0, phosphate buffer), 329 m^ (0.1 

 N NaOH). pKa = 2.2, 7.0, and 10.9. Infrared spec- 

 trum of crystal III given in references 1 and 3. 

 Rf value = 0.86 (l-butanol saturated with 0.05 

 M pH 7.0 phosphate buffer) (3). Rf (n-butanol 

 and acetic acid) = 0.28 (2). Soluble in dilute acid. 

 Negative Molisch, biuret, Sakaguchi, ninhydrin, 

 FeCls , and Fehling tests. Positive Ehrlich and 

 Bratton-Marshall tests (both for arylamino 

 groups) (2). Gives insoluble precipitates with 

 picric, picrolonic, styphnic, and phosphotungstic 

 acid. A hydrochloric acid solution reacts with 

 nitrous acid giving a diazo compound (I). This 

 reacts with N-(l-naphthyl)ethylenediamine to 

 give a violet color with a maximum at 550 mju. 

 Alkaline hydrolysis products include cytosa- 

 mine. Acid hydrolysis product is p-aminoben- 

 zoylcytosine. CooHjsNsOt : C = 57.69%; H = 

 6.84%; N = 13.52% (1). Structural formula given 

 in Chapter 6. 



Biological activity: Active on gram-positive bac- 

 teria, including mycobacteria. Negligible activity 

 on gram -negative bacteria and fungi. Has less 

 activity in vitro and in vivo on M. lubercidosis 

 H37Rv than amicetin or baniicetin (3). 



References: 



1. Sensi, P. et al. Antilnotics & Chemother- 



apy 7: 645-052, 1957. 



2. British Patent 707,332, April 14, 1954. 



3. Haskell, T. R. et al. J. Am. Chem. Soc. 

 80: 743-747, 1958. 



LiiiKloni'v cin 



Produced by: Streptornyces sp. (1). 



Synonym: Resembles valinomycin (1, 2). 



Method of extraction: Broth and mycelium 

 treated with a filter-aid, the pH adjusted to 3.5 

 with concentrated HCl, and filtered. The solid 

 residue is extracted with methanol. Methanol 

 removed by evaporation in vacuo at 40°C; the 

 residual suspension diluted with water and freeze 

 dried. Solid extracted in a Soxhlet apparatus for 

 3 to 6 hours with petrol (b.p. 30-60°C). Petrol 

 evaporated to dryness, giving an oily residue 

 which partially crystallizes on standing. Recrys- 

 tallization from petrol or 50 per cent aqueous 

 ethanol. Increased yields can be obtained by 

 chromatographing benzene solutions of the dried 

 mother litpiors on silicic acid and developing 

 with benzene, then chloroform. In large fermen- 

 ters, most of the activity is in the broth (1). 



Chemical and physical properties: Neutral, 

 colorless needles; m.p. 192 °C. [a]" = +19.2° 

 (c = 1.2 per cent in ethanol). Insoluble in water; 

 partially soluble in petrol; very soluble in organic 

 solvents. Sta))le. No characteristic absorption in 

 ultraviolet or visible light. Infrared absorption 

 spectrum given in reference 2. Hydrolysis in alco- 

 holic acid or alkali, followed by treatment with 

 concentrated HCl, gives two products, D(— )- 

 valine and D( — )-a-hydroxyisovaleric acid, both 

 biologically inactive. Rf values of 0.86 (paper 

 impregnated with ethylene glycol, with petrol, 

 b.p. 100-120°C as mobile phase); 0.90 (water- 

 saturated n-amyl alcohol); 0.36 (ethjd alcohol- 

 acetic acid-water, 3:1:6); and 0.89 (ethanol- 

 water, 2:3). C = 60.22%,; H = 8.62%; N = 7.06%; 

 C-Me = 31.7%. C40H68O12N4 . Chemical structure 

 shown at top of p. 187. 



Biological activity: Active on yeasts and fila- 

 mentous fungi. Resistance does not develop 

 readily. Not active on bacteria (1). 



References: 



1. Taber, W. A. and Vining, L. C. Can. J. 



:\Iicrobiol. 3: 953-965, 1957. 



2. Vining, L. C. and Taber, W. A. Can. J. 



Chem. 35: 1109-1116, 1957. 



Amphoniyciii 



Produced by: Streptornyces canus (1, 3), S. vio- 

 laceus (5), and a Streptornyces sp. resembling S. 

 lavendulae (5). 



Synonym: Closely related to crystallomycin 

 and aspartocin. 



