DESCRIPTIONS OF ANTIBIOTICS 



203 



buff-colored henzylamine salt. A 50 per cent aque- 

 ous methanol solution of this salt is adjusted to 

 pH 2.5 and extracted with ether; this gives free 

 base on evaporation to dryness (1). 



Chemical and physical properties: Labile, lac- 

 tonic acid (I) has a biologically active, stable, 

 crystalline monobenzj-lamine salt (II). It is a 

 colorless, amorphous powder which darkens on 

 standing, [afo = —161° (c = 1 per cent in metha- 

 nol). Ultraviolet absorption spectrum has one 

 peak at 218.5 ni/n (E'l^m 358). Positive permanga- 

 nate and bromine tests. Negative FeCh (yellow- 

 green), Fehling, 2,4-dinitrophenylhvdrazine, Tol- 

 len alcoholic silver nitrate, and sodium hypoiodite 

 tests. No S, N, or halogens. CieHis-aoOs : C = 

 64.67%; H = 6.29%, 2 methyl groups, but no 

 methoxyl group. pKa = 5.3 (50 per cent aqueous 

 ethanol). Neutral equivalent, 292. Soluble in most 

 organic solvents. Insoluljle in water. Infrared 

 spectrum given in reference 1. II: m.p. 128-131°C. 

 [a]v, = —130° (c = 1 per cent in methanol). Neu- 

 tral equivalent, 373. pKa = 8.9 (50 per cent aque- 

 ous ethanol). Infrared spectrum in reference 1. 

 Soluble in methanol. Slightly soluble in water and 

 ethyl acetate. Insoluble in he.xane and ether (1). 



Biological activity: Active on gram-positive bac- 

 teria including Clostridium perfringetis, Strepto- 

 coccus pyogenes, D. pneumoniae, Erysipelothrix 

 rhusiopathiae . and Corynebacterium diphtheriae 

 (0.19 to 0.78 Mg per ml). Less active on Staph, 

 aureus strains resistant to other antibiotics. Mod- 

 erately active on some gram-negative bacteria, 

 including E. coli. Not active on mycobacteria. 

 Very active on Trichomonas vaginalis and Enda- 

 moeba histolytica. Slightly active on yeasts and 

 saprophytic fungi; moderately active on phyto- 

 pathogenic fungi. In vivo, toxicity is too great to 

 give effective doses (2). 



Toxicity: LDso (mice) 12.5 mg per kg subcu- 

 taneously, 25 mg per kg orally (2). 



Utilization: Possibly against plant di-sease (2). 



References: 



1. Koe, K. B. e/ a?. Antibiotic.-^ Ann. 672-075, 



1956-1957. 



2. English, A. R. et al. Antibiotics Ann. G76- 



681, 1956-1957. 



Antibiotic PA 147 



Produced by: Streptomyces sp. 



Method of extraction: Broth-filtrate extracted 

 with methyl isobutyl ketone. Extracts concen- 

 trated in vacuo. Back-extracted into pH 6.8 phos- 

 phate-acetic acid buffer. Buffer adjusted to pH 2 

 and e.xtracted with ethyl acetate. Extract concen- 

 trated in vacuo. Purified by chromatography on 



alumina from ethyl acetate concentrate. Forms a 

 crystalline barium salt. 



Chemical and physical properties: (3-Carbo.xy- 

 2,4-pentadienal lactol.) Ba salt: Faintly yellow, 

 crystalline powder. Cr-HioOe-BaHoO: C = 35.83%; 

 H = 3.12%; Ba = 34.03%; H^O =3.10%; CH3-C = 

 2.24% ; CH3CO = 3.08%. Optically inactive. Ultra- 

 violet absorption spectrum maximum at 272 mfx 

 {e = 2200). F/eeacrrf.'CeHeO.'i. Ultraviolet maximum 

 272mAi (e = 17200). Reacts with benzylamine to give 

 a purple-red solid. Structural formula of free acid 

 given in Chapter 6. H ydrogenation product: Color- 

 less oil; b.p. 120-125°C. Optically inactive. 



Biological activity: Ba salt has weak activity 

 against Pasteurella niultocida (62.5 Mg per ml). 

 Even less active on other bacteria (mainly gram- 

 positive bacteria and Hemophilis). Not active on 

 yeasts (2). 



Toxicity: Free acid: LD50 (micej 315 mg per kg 

 (route unknown) (2). 



References: 



1. Els, H. et al. J. Am. Chem. Soc. 80: 878- 



880, 1958. 



2. Sobin, B. A. Personal communication, 1958. 



Antibiotic PA 150 



Produced by: Streptomyces sp. (2). 



Method of extraction: Mycelium extracted with 

 water-saturated butanol. Extract concentrated in 

 vacuo until antibiotic precipitates. Purification by 

 fractional precipitation from a methanolic calciiun 

 chloride solution with water, followed by conver- 

 sion to a crystalline salt {e.g., monosodium or 

 triethylamine sulfate double salt). Precipitation 

 of the crystalline amphoteric form from an aque- 

 ous alcohol solution of the salt by neutralization 

 with dilute acid or alkali and cooling (2). 



Chemical and physical properties: Amphoteric 

 heptaene. Yellow substance. Antibiotic and salts 

 show gradual darkening and decomposition up to 

 260°C. Slightly soluble in pyridine and dimethyl- 

 formamide; less soluble in methanol, ethanol, 

 propanol, butanol, and dioxane. Insolul^le in 

 water, acetone, methyl isobutyl ketone, ethyl ace- 

 tate, chloroform, benzene, and methyl cyclohex- 

 ane. Solubility in alcohols enhanced by water. 

 Triethylamine sulfate and sulfate salts soluble as 

 above. HCl and monosodium salts more soluble 

 in polar solvents. Ultraviolet absorption spectrum 

 maxima at 340, 358, 377 (EiL 1033), and 397 m/x 

 (80 per cent aqueous methanol). [a]f,^ = +294° 

 (pyridine) or —34° (dimethylformamide-0.1 N 

 HCl). Po.sitive Fehling and 2,4-dinitrophenyl- 

 hydrazine tests. Weakly positive ninhydrin test. 

 Blue color in concentrated H2SO4 . Infrared spec- 



