408 



DESCRIPTIONS OF ANTIBIOTICS 



antibiotic on ionophoresis. The hydrochloride of 

 A, however, was not inactivated during purifica- 

 tion. Xanthomycin A (i.e., inactive mixture) : Deep 

 red amorphous substance with a bitter taste. 

 Ultraviolet absorption spectrum maxima (abso- 

 lute ethanol) at 288 (E\L 148) and 460 m^ {E\f^ 

 118), and two inflections at 225 and 315 m^ (6). 

 Infrared spectrum given in reference 6. Two 

 weakly basic groups at pK 2.0 and 4.5 (6) or one 

 at 4.8 (10). Evanescent purple color, changing to 

 yellow in alcoholic sodium ethoxide. C23H29-31- 

 N3O7 : C = 60.28%; H = 6.44%; N = 8.88% (6). 

 Xanthomycin A hydrochloride: Bright orange-yel- 

 low rectangular plates (6) or crystalline red-yel- 

 low powder; m.p. 120-125°C (decomposition) (9). 

 Very soluble in water and methanol (1). Acidic 

 solutions are yellow; alkaline are deep red. Color 

 change is reversible with loss of activity. On con- 

 tact with air, the alkaline red solutions change 

 irreversibly to yellow (6). Ultraviolet absorption 

 spectrum maxima at 264 to 267 and 325 to 327 niyu 

 (c = 4.5 mg per 100 ml of water) (1) or at 264.5 

 (El'L 179.4) and 335 m/x (E\L 18.8) (water, pH 2.0). 

 In alkali, the ultraviolet spectrum is altered, but 

 reverts to normal on re-acidification (2). In 0.1 X 

 HCl, a maximum at 265 m^, with a plateau at 340 

 to 380 mn having a maximum at 345 niju, was re- 

 ported (6). Infrared spectrum given in references 

 6 and 10. [aif = +115° (c = 0.4 per cent in water) 

 (6). pK = 3.0 and 7.3 (10). Negative Sakaguchi, 

 ninhydrin, Molisch, FeClj , nitroprusside, acidi- 

 fied stannous chloride, fuchsin, cysteine, maltol, 

 Millon, and Tollen tests (1, 9). Doubtful biuret 

 test (9). Positive Benedict, Bra in CCU , KMnOi , 

 silver nitrate, acidified KI sodium hydrosulfite, 

 and periodic acid tests. Reduces alkaline ferri- 

 cyanide (Park-Johnson). Slight precipitate with 

 2,4-dinitrophenylhydrazine and dimedone. Red 

 solution in hydroxylamine. Can be reduced with 

 loss of color and activity; color but not activity 

 returns on shaking in oxygen. Destroyed by ultra- 

 violet light (2, 3). Most stable at pH 1.0 at 100°C 

 for 25 minutes (1). C23H29-3iN307-2HCl: C = 

 51.85%; H = 6.48%; N = 7.88%; CI = 13.14% 

 (6, 10). C3oH4oN40n-3HCl: C = 48.54%; H = 

 5.06%; N = 7.84%; CI = 13.86% (9). Contains one 

 methoxyl, one methylimide, and two terminal 

 methyl groups (6). Reineckate: Long orange nee- 

 dles; m.p. 165-170°C (decomposition) (1, 2) or 

 190-195°C (4). Very soluble in acetone. Soluble 

 in warm methanol. Insoluble in cold water. CssHjt- 

 N,20i3S4Cr: C = 42.68%,; H = 5.4%; N = 15.43%; 

 S = 12.1%. Molecular weight, 742 (1). Or C29H42- 

 N907S4Cr: C = 43.22%; H = 5.28%; N = 15.49%,; 

 Cr203 = 10.77% (2). Picrate: Dark, reddish brown, 



amorphous powder. Decomposes at 117-120°C (9). 

 Sulfate: m.p. 189-195°C (decomposition). Xantho- 

 mycin B: Not obtained in crystalline form. Hy- 

 drochloride is yellow and has similar solubility 

 properties to those of A (1). Free B is more soluble 

 in water than A and C. Yellow at acidic and pink 

 at alkaline pH. Ultraviolet absorption spectrum 

 maxima at 290 and 330 niM (pH 1-0 or 6.0). At pH 

 11.0, has a single peak at 280 m^u. Reduces alkaline 

 ferricyanide. Xanthomycin C: Relatively inactive 

 substance occurring in minor amounts and be- 

 lieved related to A and B. Less water-soluble than 

 A or B. Has a single peak at 265 to 275 m/j. at pH 

 1.0 to 6.0, and a single peak at 280 m/x at pH 11.0 

 (3). Acid hydrolysis of A gives ethanolamine, 

 methylamine (7, 8, 10), ammonia, and a large 

 amount of dark brown humin-like material (7, 8). 

 Tetrahydroxanthomycin A can be methylated 

 with simultaneous hydrogenation to give a methyl 

 ether. Methyl ether can be oxidized in neutral 

 KMn04 , acidified, and extracted with ether. 

 Ether-insoluble fraction contains xanthomycinic 

 acid I, C7H11N3O10 , colorless prisms, m.p. 147- 

 148°C, with primary amide and carboxyl groups; 

 and xanthomycinic acid II, C4H3O3 , long colorless 

 needles, m.p. 118-119°C (7). 



Biological activity: Very active on gram-positive 

 and gram-negative bacteria (1, 2). Not active on 

 yeasts or fungi (5). Active in contact tests (in 

 mice) on Toxoplasma gondii (9). 



Toxicity: LD50 (mice) 160 Mg pei' kg (1) or 100 

 Mg per kg (2) intravenously. 



References: 



1. Thorne, C. B. and Peterson, W. H. J. Biol. 



Chem. 176: 413-428, 1948. 



2. Mold, J. D. and Bartz, Q. R. J. Am. Chem. 



Soc. 72: 1847-1849, 1950. 



3. Rao, K. V. and Peterson, W. H. 12th 



Intern. Congr. Pure Appl. Chem. 282- 

 283, 1951. 



4. Hosoya, S. e/ «?. J. Antibiotics (Japan) 4: 



467-4()9, 1951. 



5. Hosoya, S. et al. Japan. J. Exptl. Med. 22: 



135-138, 1952. 



6. Rao, K. V. and Peterson, W. H. J. Am. 



Chem. Soc. 76: 1335-1340, 1954. 



7. Rao, K. V. ('/ al. J. Am. Chem. Soc. 77: 



4327-4330, 1955. 



8. Dougall, D. K. and Abraham, E. P. Na- 



ture, London 176: 265, 1955. 



9. Okami, Y. et al. J. Antibiotics (Japan) 



8A: 126-131, 1955. 

 10. Dougall, D. K. J. Chem. Soc. 628-633, 

 1957. 



