DESCRIPTIONS OF ANTIBIOTICS 



385 



tion, and desorbed bj' gradient elution with water 

 to 50 per cent ethanol. Active fractions concen- 

 trated, then chromatographed on Dicalite (lower 

 phase of an ethyl acetate-cyclohexane-pH 5.0 

 Mcllvaine's buffer (7:1:8) as solvent and the 

 upper phase as developer). Active fractions con- 

 taining streptovitacin A are azeotropically dis- 

 tilled and freeze dried. A can be crj^stallized from 

 acetonitrile. Recrystallized from acetonitrile, 

 n-butanol, ether, and ethjd acetate. Can also be 

 purified by countercurrent distribution (n-amyl 

 alcohol -isoamyl alcohol -water, 12:17:29) (2). B 

 can be crj^stallized from n-butanol-cyclohexane, 

 and recrystallized from acetonitrile-ether. 



Chemical and physical properties: Complex with 

 five components, two major isomeric ones, A and 

 B, and three minor, C, D, E (1). Neutral sub- 

 stances. Streptovitacin A: Exists in two crystalline 

 modifications (crystallographic data given in ref- 

 erence 2). Orthorhombic form shows transforma- 

 tion to the monoclinic form at 147°C. Monoclinic 

 form melts at 156-161°C. Soluble in water; less 

 soluble in polar organic solvents; essentially in- 

 soluble in nonpolar solvents. Only end-adsorption 

 in ultraviolet light. Infrared spectrum given in 

 reference 2. Little rotation at the sodium D line; 

 optical activity in dioxane shown by rotary dis- 

 persion curve in reference 2. Stable at 70°C for 60 

 days in dry form. Relatively stable in aqueous 

 solution at acidic but not alkaline pH (2). Rf = 

 0.38 on paper chromatographj' (water-saturated 

 ethyl acetate, paper impregnated with 0.1 .1/ phos- 

 phate solution at pH 4.0) (1). CioHmNO.:, : C = 

 60.71%; H = 8.05%; N = 4.73%; O = 27.00%; 

 C— CHs = 7.7% (2). No titratable groups. Alka- 

 line degradation products include ammonia, a 

 small amount of 2,4-dimethyl-2-cyclohexanone, 

 and hydroxydimethylcyclohexanone. A is 3-[2-(5- 

 hydroxy - 3,5 - dimethyl - 2 - oxocyclohexyl) - 2 - 

 hydroxyethyl] glutarimide (see structural formula 

 below). Monoacetate: m.p. 165-168°C (7). Strepto- 

 vitacin B: Crystalline substance; m.p. 124-128°C. 

 Solubilities probably the same as A. Only end- 

 absorption of ultraviolet light. Infrared spectrum 

 and optical activit.y given in reference 2. Rf = 

 0.45 (same system as for A). C16H23NO5 : C = 

 60.66%; H = 7.87%; N = 4.71%; O = 27.57%; 

 C— CH3 = 8.6% (2). B is 3-[2-(4-hydroxy-3,5- 

 dimethyl - 2 - oxocyclohexyl) - 2 - hydroxyethyl]- 

 glutarimide (see structural formula below). Di- 

 acetate: m.p. 155-158°C (7). Streptovitacin C-z and 

 streptovitacin D: C2 : m.p. 91-96°C. C = 60.53%; 

 H = 7.98%; N = 4.67%; O = 27.71%; C— CH3 = 

 8.2%. C2 is 3-[2-(3-hydroxy-3,5-dimethyI-2-oxo- 

 cyclohexyl)-2-hydrox3'ethyl] glutai'imide. 1): Ring- 



hydroxylated cycloheximide; m.p. 67-69°C. C = 

 60.42%; H = 7.89%; N = 4.83%; O = 27.00%; 

 C— CH., = 9.0%. For both: C15H23NO5 (7). 



O 



o 



R" CH3 



Streptovitacin A: R = R' = H; R" = OH. 

 Streptovitacin B: R = R" = H; R' = OH. 

 Streptovitacin C: R' = R" = H; R = OH (7). 



Biological activity: Streptovitacins A and B: Ac- 

 tive on Sacch. pastorianus at 5 Mg per ml. Active 

 on Trichomonas vaginalis (1). In vivo: Active, if 

 given 24 hours after implantation, on sarcoma 180 

 (ascites), Ehrlich ascites carcinoma (some effect 

 on solid forms at high doses) in mice. Walker 

 adenocarcinoma (rat), Gu^rin adenocarcinoma 

 (rat), Jensen sarcoma (in rats), RC carcinoma, and 

 leukemia L-4946 (mice). Not effective on the 

 Murphy-Sturm lymphosarcoma. Less effective on 

 established tumors. Affects the ability of sarcoma 

 180 to regenerate (4, 5). Active on Eagles's KB epi- 

 dermoid carcinoma in tissue culture (6). 



Toxicity: Symptoms at high dose levels include 

 listlessness, diarrhea, and hematuria (4). 



References: 



1. Sokolski, W. T. e/r//. Antil)iotics Aim. 1958- 



1959, pp. 551-554. 



2. Eble, T. E. et al. Antibiotics Ann. 1958- 



1959, pp. 555-559. 



3. Herr, R. R. Antibiotics Ann. 1958-1959, 



pp. 560-564. 



4. Evans, J. S. el al. Antibiotics Ann. 1958- 



1959, pp. 565-571. 



5. Field, J. B. et al. Antibiotics Ann. 1958- 



1959, pp. 572-579. 



6. Smith, C. G. Proc. Soc. Exptl. Biol. Med. 



100: 757-759, 1959. 



7. Herr, R. R. J. Am. Chem. Soc. 81: 2595- 



2596, 1959. 



Streptozotociii 



Produced by: Streptomyces achromogenes var. 

 128 (1). 



Method of extraction: Filtration of broth at pH 

 4.0. Broth concentrated in vacuo to 0.08 volume 

 and added to 5 volumes of acetone. Precipitate 

 discarded. Acetone concentrated to an aqueous 

 solution and freeze dried. Chromatography on 



