380 



DESCRlPi'IOXS OF ANTIBIOTICS 



mulas: C24H2oOgN4 or C24H0.2O8X4 . Weak acid. 

 Infrared absorption spectrum given in reference 1. 

 Maxima of light absorption in methanol at about 

 380 an<l 245 m^. Stable at room temperature for 24 

 hours and at 100°C for 15 minutes between pH 2.0 

 and 7.0. Above pH 8.0, decomposition occurs. Pho- 

 tosensitive at pH 7.0 and higher. Dark greenish 

 brown alcoholic FeCls test. Deep yellow color in 

 concentrated sulfuric acid. In aqueous sodium hy- 

 droxide, the solutions are dark greenish brown, 

 changing to red with evolution of ammonia. 

 Orange-red precipitate with 2,4-dinitrophenj-l- 

 hydrazine. 



Biological activifi/: Active against gram-positive 

 and gram-negative bacteria. Very active against 

 adenocarcinoma 755 in mice and against HS No. 1 

 in rats. Moderately active against sarcoma 180 

 and leukemia 1210. 



Reference: 1. Rao, K. V. and Cullen, W. P. 

 Antibiotics Ann. 1959-19()0, pp. 950-953. 



Streptothricin 



Produced by: Sireptomyces laveitdulae strains (1, 

 3, 15), Sireptomyces sp. (15, 17, 18), Sireptomyces 

 (jriseus f. farinosus (32). The culture described in 

 reference 17 may also produce streptomycin; the 

 one described in reference 18 may also produce 

 streptolin. 



Synonym: See streptothi'icin-like antibiotics. 



Method of extraction: Adsorl)ed from broth-fil- 

 trate on activated charcoal at neutral pH. Eluted 

 with dilute mineral acid (A) , acidified ethanol (B) , 

 or formic acid in aqueous methanol (C) . Eluates 

 A or B neutralized, then concentrated in vacuo at 

 50°C. Residue taken up in absolute ethanol, fil- 

 tered, evaporated, then taken up in water (1, 3, 

 13). Eluate C concentrated in vacuo; methanol and 

 acetone added in excess to precipitate crude strep- 

 tothricin (13). Precipitated as phosphotungstate 

 or picrate, then purified by salt conversion (11, 13, 

 20, 23). Fractional crystallization of a pure rein- 

 eckate (11) or crystalline helianthate (12). Puri- 

 fication by chromatography on alumina (20) or a 

 Darco G-60-filter paper pulp mixture, with metha- 

 nol as solvent and developer in both instances (13). 

 Can also be chromatographed on an activated- 

 carbon column from a neutral aqueous solution 

 and eluted with very dilute acetone (1 per cent; 

 volume per volume ) (27, 34). 



Chemical and physical properties: Tribasic sub- 

 stance (27). Sulfate: Amorphous white powder. 

 Decomposes at 213-217°C. Soluble in water and 

 dilute mineral acids. Destroyed by strong acid. 

 Insoluble in ether, petroleum ether, and chloro- 

 form (1). Ultraviolet absorption spectrum shows 



only end-al)sorption (11). Positive Benedict, Tol- 

 len, neutral KMn04 , Fehling (boiling), biuret, 

 ninhydrin, Pauly, Elson-Morgan, and anthrone 

 (weak) tests. Negative Hopkins-Cole, Millon, 

 FeCls , nitroprusside, Molisch, Sakaguchi, and 

 Schiff tests (11, 27). pKa values of 7.1, 8.2, and 10.1 

 (27). Van Slyke N = 20 to 25%. No O— CH3 , 

 N — CH3 , or acetyl groups (11, 27). Hydrochloride: 

 White powder, [a]^ = — 49°(c = 1 per cent in 

 water) (13, 20). C2oH34Ns09-3HCl: C = 38.22%; 

 H = 5.79%; N = 17.79%; CI = 16.34% (27). Ther- 

 mostable. More stable to acid than to alkali (11). 

 Reineckate: Clusters of fine platelets. Sinters at 

 184 °C; decomposes at 192-194 °C. C2iH390.3NnS8Cr2 

 (base: C .,H2.507N5) : C = 24.95%; H = 4.12%; 

 N = 24.0%; Cr = 10.32%; S = 25.8% (11). Heli- 

 anthate: m.p. 220-225°C (decomposition) (12), or 

 225-230°C (13). Streptothricin also forms crystal- 

 line complex salts with calcium chloride and other 

 alkaline earth metal halides. H ydrochloride-C aCli 

 complex: m.p. about 225 °C (decomposition). 

 [a]f = -46.5° (c = 0.95 per cent in water) (20). 

 Streptothricin cannot be hydrogenated (27). Acid 

 hydrolysis products include: L-/3-h'sine, streptoli- 

 dine, and2-amino-2-desox3'-a,D-gulose. 



NH2 H H NHo H 



H— C C— C— C- 



-C— COOH 



H H H H H 



Scheme 11. L-^-Lysine (/3,e-diamino-n-caproic- 

 acid). 



COOH 



-C- 



-C— CHoNHo 



I 

 OH 



H2N 



Scheme 12. Streptolidine (roseonine, geamine): 

 2-amino-4-(l-carboxy-l-hydroxy-2-amino)ethyl-2- 

 imidazoline. 



H— C— OH 

 H— C— NH2 

 H— C— OH 

 HO— C— H 



H— C— O — 



I 

 CH2OH 



Scheme 13. 2-Amino-2-desoxy-a-D-gulose (a-D- 

 gulosamine). 



