DESCRIPTIONS OF ANTIBIOTICS 



307 



nol. Extract concentrated. Addition of ether to 

 concentrate for precipitation. III. Mycelial ex- 

 tract (hot methanol) evaporated to dryness under 

 reduced pressure. Broth-filtrate acidified to pH 

 3.5 to 4.0 with dilute H.3PO4 . Resulting precipitate 

 and residue from mycelial extraction treated with 

 1 per cent neutral sodium phosphate buffer. Buffer 

 extracted with n-butanol; butanol evaporated to 

 dryness in vacuo at 45°C. Residue taken up in 

 methanol; concentration in vacuo. Addition of 

 ether to residual solution gives musarin (3). 



Chemical and physical properties: Acid. Yellow- 

 ish or colorless substance. Sodium or potassivun 

 salts soluble in water, methanol, ethanol, and 

 butanol; insoluble in ether and acetone. Acid 

 precipitable with HCI, H.,P()4 , or H2SO4 from 

 neutral solution. Form? inactive precipitates with 

 BaCh , HgCls , or copper acetate. Free acid is 

 unstable as dry powder; sodium salt is stable. 

 Activity unaltered at pH 2 or 11 at room tempera- 

 ture for 30 minutes, but destroyed at 100°C under 

 these conditions. Sodium salt: Decomposes at 

 about 170°C without melting. [a]f = +35.1° ± 

 l.t)° (c = 1.21 per cent in methanol). Ultraviolet 

 absorption spectrum maxima at 240 m^u {E\"cm 375) 

 and 267 mn (E^lm 200) (ethanol). Free acid: C = 

 57.75%; H = 8.34%; N = 3.70%. C:ioHcnOnN, . 

 No S, P, or halogens. Equivalent weight about 

 5000. Negative Molisch, Millon, biuret, Salkowski, 

 Liebermann (steroids and cholesterol), and murex- 

 ide tests. No color with H2SO4 in acetic acid or 

 with I2 . Positive Axenfeld (protein) test (3). Fails 

 to pass a porcelain filter (2). Treatment with 

 methanol containing a few drops of methanolic 

 HCI gives an inactive product, soluble in acetone 

 and chloroform but insoluble in 1 per cent neutral 

 phosphate buffer, [a]^ = +32.2° ± 2.0° (c = 0.995 

 per cent in methanol) (3). 



Biological activity: Active against certain fungal 

 l)lant pathogens including fusaria, gram-positive 

 i)acteria, and mycobacteria. Not active on gram- 

 negative bacteria (3). 



References: 



1. Meredith, C. H. Phytoi)athology 33: 403, 



1943. 



2. Thaysen, A. C. and Butlin, K. B. Nature, 



London 156: 781-782, 1945. 



3. Arnstein, H. R. V. et al. J. Gen. ^licrobiol. 



2: 111-122, 1948. 



4. Mfg. Chemist 22: 47, 1951. 



.Mutoniycin 



Produced by: Streptomyres utroolivaceus var. 

 mutomycini. 



Method of extraction: The antibiotic is present 

 mainly in the mycelium liut can be extracted to a 



les.ser extent from the broth. To extract from the 

 broth, the mycelium is filtered off and the litiuid 

 acidified with HCI to pH 3.0. A precipitate forms, 

 which is extracted with acetone (neutralized with 

 NaOH to pH 7.0). The acetone-extract is clarified 

 with 0.4 per cent charcoal and evaporated at 40°C. 

 During concentration, the antibiotic precipitates 

 out. Precipitate dissolved in chloroform at 45°C. 

 After concentration of the chloroform, the anti- 

 biotic is precipitated by addition of 5 volumes of 

 petroleum ether. Repeated crj^stallization from a 

 65:35 chloroform-benzene mixture. From the 

 mycelium, the antibiotic is extracted with acetone. 

 Acetonic extract jjurified further as indicated 

 above. 



Chemical and physical properties: White powder 

 consisting of needle-shaped crystals; m.p. 141.5- 

 142.0°C. Insoluble in water, ether, 5 per cent so- 

 dium hj^droxide, sodium carbonate, and hydro- 

 chloric acid. Soluble in ethanol and acetone and 

 to a lesser extent in chloroform and benzene. Solu- 

 bility is increased in organic solvents by a reduc- 

 tion of the pH, but the antibiotic is less stable at 

 acid than at alkaline pH. Molecular weight 

 (Rast), 124. C = 65.5%; H = 9.1%; O = 25.5%. 

 Suggested empirical formula: C7H11.1...O2 . No 

 characteristic light alisoi-jjlion in the ultraviolet 

 range. 



Biological activity: Active against respiratory- 

 deficient mutants of sta{)hylococci. Not active 

 against other liacteria. Slightly inhil)its Ehrlich 

 carcinoma in mice. 



Toxicity: Mice tolerate single oral or subcu- 

 taneous injection of 0.5 to 1.0 gm per kg. 



Reference: 1. Cause, C. F. Antibiotiki 4(3): 

 20-23, 1959. 



M_> celiii 



Produced by: Streptoniyces roseoflavus (1), and 

 possibly by S.fradiae (dextromycin-producer) and 

 iS. diastatochromogenes (3). 



Method of extraction: Mycelium extracted with 

 methanol, ethanol, or acetone. Methanol-extract 

 concentrated in vacuo. Ethanol and Ba(OH)2 

 added to precipitate impurities. Ba"^"^ removed 

 with CO2 . Alcohol layer concentrated to precip- 

 itate mycelin. Chromatographed on alumina from 

 acetone (1). 



Chemical and physical properties: Prisms. Black- 

 ens at 260°C and decomposes at 263°C. Soluble in 

 chloroform, butanol, methanol, ethanol, amy] 

 alcohol, acetone, and benzene. Insoluble in water, 

 ether, and petroleum ether. No N or S. Negative 

 Molisch test. Stable to heat and acid, and to alkali 

 in aqueous acetone solution (1). 



Biological activity: Active on filamentous fungi; 



