316 



DESCRIPTIONS OF ANTIBIOTICS 



Neonocardin 



Produced hy: Xocaidia kuroishi (2). 



Method of extraction: Broth containing mycelium 

 heated to 100°C for 20 minutes, then cooled and 

 filtered. Treated with diatomaceous earth at pH 

 2.0, then ad.'^orbed on activated carVjon at pH 5 

 to 7. Carbon washed with water, methanol, and 

 ether. Elution into 0.04 .V HCl-methanol. Addi- 

 tion of ether to eluate precipitates neonocardin. 

 Reprecipitated from absolute methanol with 

 ether. Can be extracted from the dried mycelium 

 with distilled water (3). 



Chemical and physical properties: Hydrochloride: 

 Yellow-gray or grayish white powder (3). Found 

 to differ from other known antibiotics on paper 

 chromatography (4). 



Biological activity: Culture-filtrate active on 

 gram-positive and gram-negative bacteria (1). 



Toxicity: Mice tolerate 2 mg intraperitoneally 

 (3). 



References: 



1. Uesaka, I. J. Antil)iotics (Japan) 3: 



27-34, 1950. 



2. Uesaka, I. J. Antibiotics (Japan) 5:75-79, 



1952. 



3. Uesaka, I. J. Antibiotics (Japan) 5: 154- 



159, 1952. 



4. Ueda, S. and Uesaka, I. J. Antibiotics 



(Japan) 5: 170-171, 1952. 



Netropsin 



Produced by: Streptoniyces netropsis (2), Sirepto- 

 myces sp. resembling S. netropsis (7, 12), Strepto- 

 niyces sp. (6, 13), S. amhofaciens (6), Streptoniyces 

 sp. belonging to the S. reticuli group (15), Strepto- 

 niyces sp. (16). 



Synonyms: Antibiotic lA-887 (7), sinanomyciii 

 (12), congocidin (11, 13), antibiotic T 1384 (13), 

 antibiotic K 117 (16). 



Method of extraction: I. Broth-filtrate stirred 

 with ammonium oxalate at pH 6.5 to precipitate 

 Ca"*"*", then stirred with orange II at pH 5.5 to 

 precipitate the antibiotic. Dye precipitate fil- 

 tered with Super-Cel, then dye dissociated from 

 the antibiotic by stirring with 80 per cent acetone- 

 20 per cent methanol containing methanolic tri- 

 ethylamine sulfate. Super-Cel-netropsin sulfate 

 mixture washed with acetone-methanol, then ex- 

 tracted with cold distilled water and BaCl-i to 

 give the HCl salt. Adjusted to pH 2.0 with H2SO4 

 to precipitate Ba"^+, then treatment with IR-4 ion 

 exchange resin to remove excess SOT- A saturated 

 aciueous solution of the amorphous product gives 

 crystals on standing (2). II. Broth-filtrate ad- 

 sorbed on IRC-50 cation exchange resin (eciuili- 



brated to pH 7.5 with NaOH). Fluted with 0.46 iV 

 HCl or methanolic HCl. Active fractions adjusted 

 to pH 6.0 and excess Ca'*^^ removed as oxalate. 

 Filtrate concentrated in vacuo, then cooled to 

 give crystals of antibiotic. Recrystallized from 

 water or methanol. Purification on alumina (3, 11). 

 III. Adsorption from broth-filtrate on acidic 

 clay at pH 7.6 and extraction of myceliimi with 

 80 per cent acetone (pH 5.0). Elution from clay 

 with 80 per cent acetone (pH 2.0). Eluate concen- 

 trated in vacuo, adjusted to pH 2.0, and lyophil- 

 ized. Solid extracted with ethanol and pre- 

 cipitated on addition of ether. Purification by 

 chromatography on alumina from ethanol-meth- 

 anol (3:1) and development with methanol. Pre- 

 cipitated from active fractions with ether (7). 



Chemical and physical properties: Unstable, di- 

 acidic base. HCl salt: Fine needles; m.p. 167-173°C 

 (decomposition) or long, thin, colorless, hydrated 

 prisms exhibiting oblique extinction. Soluble in 

 methanol and ethanol; moderately soluble in 

 water and water-saturated n-butanol. Insoluble 

 in almost all other nonpolar solvents. No optical 

 activity in water. Ultraviolet absorption spectrum 

 maxima at 295 m/. {EZn 423) and 238 niju (^llm 430) . 

 Infrared spectrum given in reference 2. Positive 

 Sakaguchi, Dragendorfi (N— CHu), Ehrlich alde- 

 hyde (3), Weber-Rose, and Bayer tests. Negative 

 ninhydrin, biuret, Tollen, Fehling, maltol, Mo- 

 lisch, fuchsinaldehyde, miu'exide, amino anti- 

 pyridine (phenol), 2,4-dinitrophenylhydrazine, 

 Elson-Morgan, FeCls , and Hanke-Koessler tests. 

 Inactivated by 0.2 A' NaOH in <2 hours at 25°C. 

 C = 42.9%; H = 5.78%; N = 28.1%; CI (total 

 and ionic) = 13.7% (2, 7, 10-12). Sulfate: Long 

 colorless needles; m.p. 224-225°C. CisH-ibNioOs- 

 i^H2S04 . More soluble in hot than in cold water. 

 Insoluble in common organic solvents. Ultraviolet 

 absorption spectrum maxima at 236 mn (£'iem 429) 

 and 297 m/x (Eum 436). Differentiated from strep- 

 tot hricin and streptomycin by paper chromatog- 

 raphy (water-saturated n-butanol containing 2 

 per cent p-toluenesulfonic acid). Hydrogenation 

 product is biologically inactive (1, 2, 7, 10). Pic- 

 rate: Sheaves of yellow needles; m.p. 205 or 232°C 

 (decomposition). Browns and sinters at 225°C 

 (1, 7, 10). Helianthate: Orange plates; m.p. 215°C 

 (decomposition) (10). :\Iild alkaline hydrolysis 

 gives either glycocyamidine or guanidinoacetic 

 acid, ammonia, and /3-[4-(4-amino-l-methyl-2- 

 pyrrolecarboxamido) - 1 -methyl -2 -pyrrolecarbox- 

 amido]propionamide (netropsinine). The latter 

 compound was also obtained from congocidin and 

 antibiotic T 1384 (10, 11, 13). Structure of netrop- 

 sin (13) given in Chapter 6. /3-[4-(4-guanidino- 



