DESCRIPTIONS OF ANTIBIOTICS 



289 



HO- 

 HO— I 



OH 



OH 



References: 



1. Patrick, J. B. el al. J. Am. Chom. Soc. T«: 



2652, 1956. 



2. Allen, i\. R., Jr. J. Am. Chem. Soc. 78: 



5691-5692, 1956. 



Hygroscopins 



Produced by: Streptoniyces hyqroscopicus (1, 2). 



Synonyms: Hygroscopiii A and elaiomycin are 

 similar or closely related. 



Method of extraction: Broth extracted with 

 butyl acetate at pH 2.0. Extract washed with 

 sodium bicarbonate solution, then concentrated 

 in vacuo. Concentrate extracted with methanol. 

 Extract chromatographed on carbon to give three 

 fractions. Fraction I (eluted with methanol) gives 

 hygroscopin B on distillation. Fraction II (eluant, 

 methanol) contains hygroscopins A and B, which 

 are separated b}^ distillation or carbon chroma- 

 tography. Fraction III (eluant, ethyl acetate) 

 gives hygroscopin C (1,3). 



Chemical and physical properties: H yi/roscopiii 

 A: Oil; b.p.„.„o3 64°C. [a]o^ = +84.7° (methanol). 

 Ultraviolet absorption spectrum maximum at 235 

 m;u (ethanol). Refractive index: no 1.4830. Ci:)H34- 

 OisN-j . Hygroscopin B: Oil; b.p.o.oos 70°C or b.p.d.o 

 108°C. [a\\* = -38.8° (methanol). Ultraviolet 

 absorption spectnun maximum at 233 m/i (etha- 

 nol). Refractive index: tiv 1.4935. Infrared spec- 

 trum given in reference 1. C10H2SO3N2 : C = 

 63.53%; H = 10.05%; N = 10.07%,. Molecvdar 

 weight, 290 ± 10. Hygroscopin (': Not charac- 

 terized (1 , 3). 



Biological activity: Hygroscopin A: Active on 

 fungi, yeasts, influenza A virus (in tissue culture), 

 and M. tuberculosis var. hominis H37Rv. Tran- 

 siently active on Yoshida sarcoma (rats) at 1 mg 

 l)er kg. Hygroscopin B: Active on influenza A 

 virus (as above) but not on fungi, yeasts, or myco- 

 bacteria. Same activity as hygroscopin A on 

 Yoshida sarcoma. 



Toxicity: Hygroscopin A: LD.^i (mice) 8.75 mg 

 per kg intraperitoneally. Hygroscopin B: Ll):,ii 

 (mice) 1928 mg per kg intraperitonealh*. 



Eeferences: 



1. Tatsuoka, S. et al. J. Antil)iotics (Japan) 



7B: 329-332, 1954. 



2. Nakazawa, K. et al. J. Agr. Chem. Soc. 



Japan 28: 296-299, 1954. 



3. Tatsuoka, S. et al. J. Antibiotics (Japan) 



8A: 31, 1955. 



Hygrostatin 



Produced by: Streptomyces hygrostaticus. 



Synonym: Similar to musarin. 



Method of extraction: Mycelium collected and 

 washed with water. Extraction from mycelium 

 with methanol or acetone. Solvent concentrated. 

 Concentrate extracted with butanol at pH 6.5. 

 Precipitation from butanol with ether. Precipitate 

 dissolved in a 1:1 mixture of benzene and metha- 

 nol, and chromatographed over alumina. Elution 

 carried out by increasing the methanol content of 

 the mixture. Further purification by coiuiter- 

 current distribution in a chloroform-methanol-pH 

 7.0 phosphate buffer system (1:1:0.5). Active frac- 

 tions evaporated and dissolved in butanol. Upon 

 addition of ether, a precipitate forms, which then 

 is dried. 



Chemical and physical properties: Pale yellow 

 powder. Decomposes 129-131 °C. Contains N but 

 no S or halogens. Very soluble in methanol and 

 pyridine. Soluble in ethanol, butanol, and iso- 

 l^ropanol. Slightly soluble in benzene, chloroform, 

 and acetone. Insoluble in ethyl acetate, ether, 

 petroleum ether, dioxane, and water. Dark red to 

 purple color with concentrated sulfuric acid. 

 Orange-brown to red-purple with concentrated 

 HCl. Negative biuret, FeChj , Benedict, ninhy- 

 drin, Fehling, and Tollen tests. Acid hydrolysate 

 also ninhydrin-negative. [a]o = -(-43° (c = 1.21 

 per cent in methanol). Light absorption maximum 

 at 240 niM (E\7m 360) and a shoulder at 255 to 270 

 nxfj.. Stable for 30 mimites at 100°C at neutrality. 

 Unstable at acid and alkaline pH values. 



Biological activity: Active against filamentous 

 fungi, yeasts, and gram-i)ositive bacteria. Inactive 

 against gram-negative bacteria and Clostridia 



Toxicity: LD50 (mice) 8.6 mg per kg intrave- 

 nously, 21.7 mg i)er kg intraperitoneally, 246.7 mg 

 per kg subcutaneously, and 530 mg per kg orally. 

 Necrosis at the site of injection. Autopsy shows 

 bleeding in the lungs. Nontoxic at 500 /xg per ml 

 when sprayed on plant leaves. 



Reference: 1. Kojo, K. et al. Yakugaku Kenkyu 

 30: 654-664, 1958. 



