302 



DESCRIPTIOX.^ OF ANTIBIOTICS 



teria. Not active on B. cereus-»n/c(>idcs grouj). No 

 activitj' on gram-negative bacteria (1, 3). 

 References: 



1. Waksman, S. A. e( al. Soil Sci. 54: 281- 



2()(), 1942. 



2. Waksman, S. A. el al. J. Bacteriol. 5.'?: 



355-357, 1947. 



3. Welsch, M. Rev. beige pathol. et med. exptl. 



Suppl. II: 18, 1947. 



Mikainyciii A 



1^ rod need by: Slreptoniyees niilakdcnsls (1). 



Synonyms: Mikamycin. The main component. s 

 of streptogramin and staphylomycin are thought 

 to be the same as those of mikamj'cin (1). 



Method of exlraclion: Broth-filtrate extracted 

 with ethyl acetate at pH 6.0. Extract washed 

 with water, with dilute HCl at pH 2.0, and with 

 NaHCCJs at pH 7.4. Solvent layer concentrated in 

 vacuo at 27-30°C. Addition to a large volume of 

 petroleum ether precipitates mikamycin. Powder 

 dissolved in methanol, filtered, and solution con- 

 centrated. Concentrate washed with ether, and 

 extracted with chloroform. Chloroform solution 

 chromatographed on HNOs-treated alumina in 

 carbon tetrachloride. Washed with benzene and 

 ethyl acetate. Eluted with methanol. Active frac- 

 tions concentrated and precipitated from ether. 

 Purification by countercurrent distribution 

 (methanol - benzene - chloroform - water, 20:25: 

 15:7). The solvent of the active fractions evapo- 

 rated in racuu and the aqueous residue extracted 

 with chloroform. Extract concentrated to dryness. 

 Redistributed countercurrently (methanol-ben- 

 zene-chloroform-water, 27:28:12:8). Active frac- 

 tions crystallized from benzene (1). 



Chemical and physical properties: Neutral. Yel- 

 lowish white crystalline substance; m.p. 178°C 

 (decomposition). C31H39O9N., : C = 62.08%; H = 

 ().5S%; N (Dumas) = 7.34%. No halogens or S. Mo- 

 lecular weight, 617. [a]^ = —152° (c = 0.5 per cent 

 in methanol). Very soluble in chloroform, metha- 

 nol, ethanol, and acetone. Soluble in methylene 

 chloride, ethylene chloride, benzene, and ethyl ace- 

 tate. Slightly soluble in ether and water. Insolu- 

 ble in petroleum ether, carbon tetrachloride, and 

 hexane. Positive Fehling and diazo tests. Negative 

 maltol, glucosamine, ninhydrin, Millon, and 

 biuret tests. Black-green color with FeClj . 

 Black-brown precipitate with ToUen test (no 

 mirror). Green color and brown precipitate with 

 Benedict test. Labile to alkaline pH; most stable 

 at pH 4.0. Ultraviolet absorption spectrum (meth- 

 anol) maximvuii at 226 ni/x (£{'''1^ 624) and an in- 

 flection at 270 niM (^'llm 200). In 0.1 N NaOH-4 



})or cent methanol, a maximvuu at 293 m^ (£'i"cm 

 462) shifts to 283 niju (^llm 201) after inactivation 

 at this pH. Acidification causes this peak at 283 

 niju to disappear. It reappears on readjustment to 

 alkaline pH. Staphylomycin and streptogramin 

 react similarly. P'orms a dinitrophenylhydrazone: 

 m.p. 160-165°C (decomposition). Infrared data 

 given in references 2 and 3. Paper chromatography 

 (3 per cent NH4CI) shows one spot (Rf = 0.59) for 

 mikamycin, two spots (Rf = 0.60 and 0.39) for strep- 

 togramin, and two spots (Rf = 0.61 and 0.41) for 

 staphylomycin (assay organism, Sarcina liitea). 

 Hydrogenation yields decahydroini kaiii yci n . which 

 has no absorption of ultraviolet light: white 

 plates; m.)). 94°C (decomposition). Contains 

 2C— CHs , IN CH.i , 2C = O, and 5C = C. 

 Monoacetafe: Biologically inactive, yellow-green 

 crystals; m.]). 138°C. Ultraviolet absorption spec- 

 trum maximum at 236 niyu ie = 42,347) and an 

 inflection at 270 m^ (e = 21,621). 2,^-Dimtro- 

 phenylhydrazone: Red crystals; m.p. 180-186°C 

 (decomposition). Acid hydrolysates of mikamycin 

 contain L-proline and glycine. An additional 

 weakly ninhydrin-positive spot was assigned to an 

 N-methyl-containing moiety. Mikamycin may 

 contain a chromophore attached to a peptide 

 chain (1 ). 



Bioloyicid activity: Active on gram-jjositive 

 bacteria (0.1 to 55 yug per ml) ; less active on myco- 

 bacteria (20 to 28 Mg per ml) (1); not active on 

 gram-negative bacteria, fungi, or yeasts. Active 

 in mice on D. pneumoniae infections (1). 



Toxicity: Mice tolerate 250 mg per kg inlraperi- 

 toneally (1). 



References: 



1. Arai, M. et al . J. Antibiotics (Japan) llA: 



14-20, 1958. 



2. Arai, M. et al. J. Antil)iotics (Japan) llA: 



21-25, 1958. 



3. Okabe, K. J. Antiliiotics (Japan) 12A:86- 



89, 1959. 



4. Watanabe, K. et al . J. Antibiotics (Japan) 



12A: 112-113, 1959. 



Mikamycin B 



Produced by: Slreptoniyees niitakaensis. 



Synotiyin: Similar to antiliiotic PA 114B. 



Remarks: Mikamycin was described as probably 

 identical with streptogramin and antibiotic 899. 

 This compound shoidd now be called mikamycin 

 A, since another antibiotic has been found to be 

 produced l)y the same actinomycete and has l)een 

 called mikamycin B. As previously observed for 

 similar antibiotics, such as PA 114, staphylo- 



