DESCRIPTIONS OF ANTIBIOTICS 



261 



polar solvents and at acidic and alkaline pH in 

 aqueous solution. Peak gradually disappears in 

 0.1 A'^ NaOH. Infrared speotrvun given in reference 

 1. [aJc = +38.4° (c = 2.8 per cent in absolute 

 ethanol). Gives a deep purple color when placed 

 in light having a wave length of 256 n^fx. ni^ = 

 1.4798. Positive iodoform test. Negative FeCln , 

 Benedict, ninhydrin, Sakaguchi, periodic acid, 

 xanthate (for OH~ groups), hydro.xamate (ester 

 groups), sodium nitroprusside (for methyl ke- 

 tone), and Ehrlich tests. Stable in neutral or 

 acidic aqueous solutions, but in 0.1 A' NaOH de- 

 composes into a yellow jiroduct of unknown char- 

 acter. C13H26N2O3 : C = 60.12%; H = 10.06%; 

 N = 10.95%. Molecular weight, 244. Acid hydrol- 

 ysis products include racemic «-hydroxyoctanoic 

 acid. Contains an aliphatic a,|8-unsaturated 

 azoxy group and exists in the l)-threo configura- 

 tion (1, 3, 6). Structural formula is given in Chap- 

 ter 6. 



Bidhxjical artivilji: Active on human and bovine 

 varieties of M . (tthcn-nlosis but not on other types 

 of mycobacteria. Very slight activity on fungi. 

 Not active on bacteria. Not active in vivo (mice 

 and guinea pigs) on tuberculosis (2). 



Toxicity: LD50 (mice) 43.7 mg per kg intra- 

 venously, 62.5 mg per kg subcutaneously (2). 



References: 



1. Haskell, T. H. et al. Antibiotics & Chemo- 



therapy 4: 141-144, 1954. 



2. Ehrlich, J. et al. Antibiotics & Chemo- 



therapy 4: 338-342, 1954. 



3. British Patent 730,341, May 18, 1955. 



4. Anderson, L. E. et al. Antibiotics A: Chem- 



otherapy 6: 100-115, 195C). 



5. Ohkuma, K. et at. J. Antibiotics (Japan) 



lOA: 224-225, 1957. 



6. Stevens, C. L. ci at. J. Am. Chem. Soc. 



80: 6088-6092, 1958. 



Kluiopli,\ liii 



Produced 1)1/: Strcptonn/cc.'i ntelariosporiis var. 

 nielanosporofaciens. The same organism ])roduces 

 melanosporin. 



Synonym: Similar to azalomycin B. 



Method of extraction: See melanosporin. 



Chemical and physical properties: White crys- 

 tals; m.p. 178-183°C (decomposition), [a];" = 

 — 49° (in chloroform). Soluble in chloroform, 

 acetone, and ethyl acetate. Slightly soluble in 

 lower alcohols. Insoluble in water, ether, and 

 benzene. Tentative empirical formula: (CeHioO)),,. 

 Light-absorption maximum at 252 m/x. Infrared 

 absorjjtion spectr(un given in reference 1. 



Biological activity: Active against gram positive 

 bacteria. 



Toxicity: Mice tolerate 100 mg per kg intra- 

 peritoneally. 



Reference: 1. Arcamone, F. M. et al. GioriK 

 mierobioi. 7: 2(17-2](i, 195i). 



FIikIoitij fins 



Produced by: Strcptomyces c/h/'/s (closely related 

 to S. hi/f/roscopicus) (7, 12), and Sti'cptomyces sj). 

 (2, 13). 



Synonyms: Helixins A and B. Related to medi- 

 ocidin. A second, nonpolyenic, ether-soluble anti- 

 biotic (9-20F-1) present in cTidomycin l)r()ths may 

 be the same as helixiu C (2, 13). 



Method of extraction: Mycelium and precipitate 

 from acidified broth extracted successively with 

 butanol. Extract evaporated with addition of 

 water. Residue treated with ether and boiling 

 benzene, then suspended in water and retreated 

 with ether. Aqueous layer (pH 8.5 to 9.0) centri- 

 fuged. Supernatant acidified to preci])itate dark 

 brown gummy antibiotic. Taken up in 0.05 A^ 

 NaOH and precipitated with glacial acetic acid; 

 or, taken up in absolute alcohol and reprecipitated 

 with amyl acetate (2, 8). May also be extracted in 

 the same way as candidin and separated into com- 

 ponents A and B l)y covuitercurrent distribution 

 (ethyl acetate-n-propanol-0.1 .V aqueous NH4AC, 

 3:1:3) (13). 



Chemical ami physical propciiiis: ('(Duplex: 

 Yellow-brown powder. Soluble in alcohols con- 

 taining 10 to 20 per cent water, methyl Cellosolve, 

 dimethylformamide, pyridine, glacial acetic acid, 

 0.2 A^ NaOH, or HCl. Soluble in water at pH 2.0 

 or below and at pH 7.0 or above; insoluble in water 

 at pH 4 to 6. Partiallj' soluble in methanol and 

 ethanol; sparingly soluble in dioxane. Insoluble 

 in ether, chloroform, benzene, ethyl acetate, ace- 

 tone, and other nonpolar solvents. Can be pre- 

 cipitated from aqueous solution by Na"*", Ca^""", or 

 Mg"'"+. Surface-active and forms emulsions easily. 

 Slowly diffusible. Low nitrogen content (about 

 3.7 per cent). Stable to acid and alkali and to auto- 

 claving at pH 7.0. pK,.,' = 2.5; pKa^ = 5.5 to 6.5; 

 pKa^ = 9. Contains two major components: A, 

 a tetraene; and B, a hexaene. A greater amount of 

 the tetraene was present in the helixin complex 

 than in the endomycin complex. The helixin I) 

 component is i)resent in varying quantities in 

 endomycin. Rf values for A and B are 0.04 and 

 0.37 (water-saturated n-butanol), 0.09 and 0.38 

 (water-saturated n-butanol on paper buffered 

 with 0.1 A' sodium phos])hate at pH 12.0). and 



