DESCRIPTIONS OF ANTIBIOTICS 



201 



teria. Not active on gram-negative bacteria or 

 yeasts. 



Toxicity: LD50 (mice) 0.35 mg per kg intrave- 

 nously. 



Reference: 1. Sensi, P. et al. Antiliiotics & 

 Chemotherapy 8: 241-244, 1958. 



Antibiotic PA 86 



Produced by: Streptomyces riniosus. 



Method of extraction: Whole culture filtered with 

 a filter-aid at acid pH. Filtrate extracted with 

 Initanol at pH 7.8 to 9.0. Butanol evaporated in 

 vacuo with addition of water, and cooled to give 

 a precipitate. Taken up in hot methanol, filtered, 

 and water added. Solvent is evaporated off until a 

 solid precipitates. May also be extracted from 

 the broth-filtrate with benzyl or amyl alcohol. 

 Recrystallized from methanol -water or hot 50 per 

 cent aqueous acetone. 



Chemical and physical properties: Tetraene. 

 White needles, small plates, or rosettes; m.p. 

 230-235°C (decomposition). Soluble in acjueous 

 alcohols. Low solubility in water, alcohols, ethers, 

 and ketones. Ultraviolet absorption spectrum 

 ma.xima at 279, 291, 304, and 318 m^. Infrared 

 spectrum given in reference 1. Optically inactive 

 in common solvents. Unstable in acid. C = 60.30% ; 

 H = 8.30%; N = 3.41%o. No S, P, or halogens. 



Biological activity: Active on yeasts and fila- 

 mentous fungi. 



Reference: 1. British Patent 719,878, December 

 8, 1954. 



Anlihiolics PA 108, PA UliX, PA l.J.JB, and 

 PA 148 



Produced by: Streptomyces sp. 



Synonyms: Macrolide-type antiljiotics related to 

 spiramycin, narbomycin, leucomycin, borrclidin, 

 and angolamycin. 



Method of extraction: Extraction of filtered broth 

 with ethyl acetate or methyl isobutyl ketone. Sol- 

 vent evaporated to dryness in vacuo. Further 

 purification by countercurrent distribution in the 

 system benzene-cyclohexane-95 per cent ethanol- 

 water, 5:5:8:2 by volume. Coefficient distribu- 

 tions in that system: PA 108 = 0.43; PA 133A = 

 1.50; PA 133B = 0.50; PA 148 = 0.17; carbomy- 

 cin = 0.41; carbomycin B = 0.67; erythromycin = 

 0.24; oleandomycin = 0.25. 



Chemical and physical properties: PA 108: 

 m.p. 121-123°C. Proposed empirical formula: 

 CssHesNOu . [a]f = -36.8° (c = 1 per cent in 

 CHCI3). Light-absorption maximum at 279 m^ 

 (£■10^289). PA 133 A: Amorphous material melts 

 at 87.2-88.0°C. Tentative empirical formula: 



C.25H4,,N06 . [a]f = +39.6° (c = 0.5 per cent in 

 methanol). Light-absorption maxima at 226 m^ 

 (Elfra 183) and at 275 m/x {Eu^ 9.0). PA 133B: 

 m.p. 99.8-101°C. Tentative empirical formula: 

 C25H45NOUJ . [a]n' = +22.5° (c = 0.5 per cent in 

 methanol). Light absorption maximum at 223 

 m^ (£'icm 184). PA 148: Amorphous material; melts 

 at 115-118°C. Tentative empirical formula: 

 CssHesNOu . [at^ = -69.3° (c = 0.5 per cent in 

 methanol). Light-absorption maximum at 238 m/x 

 (£•!;?,„ 153) with a shoulder at 280 m^- Infrared 

 absorption spectra and paper chromatograjihy 

 data given in reference 1. 



Biological activity: PA 108: About as active as 

 carbomycin against B. subtilis in a cylinder plate 

 assay. PA 133A and PA 133B: About one fourth 

 as active as carbomycin against B. subtilis in a 

 cylinder plate assay. 



Reference: 1. Murai, K. et al. Antil)iotics & 

 Chemotheraijy 9: 485-490, 1959. 



Anlihiotic PA 114 



Produced by: Streptomyces olivaceus (2). The 

 organism produced a nimiber of minor components 

 in addition to PA 114A, B, and B-3, described be- 

 low (4). 



Synonyms: PA 114A is identical to E 129A and 

 staphylomycin Mi . PA 114B is the same as E 

 129B but differs from staphylomycin S (3). 



Method of extraction: Broth-filtrate extracted 

 with methyl isol)utyl ketone or other solvents, in- 

 cluding ether, benzene, ethyl acetate, butanol, or 

 chloroform (1, 2). I'^xtract concentrated and 

 chilled with precipitation of 114A. Addition of 

 hexane to the supernatant gives a precipitate. 

 Precipitate taken up in methylene chloride. Im- 

 purities precipitated l)y addition of carbon tetra- 

 chloride and concentration. Addition of hexane 

 to the concentrate gives 114B. 114A is purified 

 by countercurrent distribution (benzene-metha- 

 nol-water, 2:1:1). 114A crystallizes from hot n- 

 butyl ethyl ketone or methanol-water. 114B and 

 114B-3 also purified by countercurrent distribu- 

 tion (toluene-methanol-water, 4:3:1). Further 

 purified by chromatography on silica gel followed 

 by redistribution countercurrently. Crystallized 

 from methanol or toluene-hexane (1,4). 



Chemical and physical properties: Complex: 

 Amorphous yellow powder. Soluble in lower alco- 

 hols, chloroform, acetone, dioxane, Vjenzene, ether, 

 and methylene chloride. Sparingly soluble in 

 water and carbon tetrachloride. Insoluble in hex- 

 ane. Infrared spectrum data given in reference 2. 

 PA II4A: Neutral polypeptide. Colorless needles; 

 m.p. 200°C (decomposition). Ultraviolet absorp- 



