DESCRIPTIONS OF ANTIBIOTICS 



371 



recrystalliziition of the helianthate of the complex 

 gives streptolin A (5). 



Chemical and physical propcrlics: Streptolin coih- 

 plex: Basic substance. Sulfate: White amorphous 

 powder. Helianthate: Crystalline; m.p. 203°C (de- 

 composition) (5). Hydrochloride: [a]^ = —22° (c 

 = 1.8 per cent in water) (1). Positive biuret, nin- 

 hydrin, Shaffer-Somogyi (copi)er reagent), and 

 Park-Johnson ferroferricyanide tests (4). Negative 

 Sakaguchi, maltol, phenylhydrazine, and 2,4- 

 dinitrophenylhydrazine tests (1, 4). Maximal 

 stability at ])H 3 to 3.5 when heated to 120°C for 

 I hour. Less stable in more alkaline or acidic 

 solutions. Diffu.ses poorly in agar (1). CnHgi-ss- 

 N50s(HCl)o or C24H45-47N70n : C = 39.95%; H = 

 6.66%; N = 13.65% (4). Contains no N-alkyl func- 

 tions (3). Streptolin A: Isomeric with streptolin 

 B. Helianthate: Crystalline; m.p. 206°C (decompo- 

 sition). Sulfate: Amorphous, [afo" = —20° (c = 1 

 per cent). Infrared spectrum given in reference 5. 

 Streptolin B: Acid hj'drolysis products include 

 L-/3-lysine, "streptolidine," and 2-amino-2-des- 

 oxy-a,D-gulose (a-D-gulosamine) (6, 8). (See 

 schemes with streptothricins.) 



Biological activity: Complex: Active on gram- 

 positive and gram-negative bacteria (1). Strepto- 

 lin B is more active than A (5). Partial cross- 

 resistance with streptothricin and, in one case, 

 streptomycin (2). Active on the nematode Rhabili- 

 tis brigcjsae (7). 



Toxicity: Complex and streptolin A: 6 mg per 

 kg injected intravenously is lethal to mice (5). 



References: 



1. Rivett, R. W. and Peterson, W. H. J. Am. 



Chem. Soc. 69: 3006-3009, 1947. 



2. Pagano, J. F. el al. Proc. Soc. Exptl. Biol. 



Med. 79: 359-363, 1952. 



3. van Tamelen, E. E. and Smissman, E. E. J. 



Am. Chem. Soc. 74: 3713-3714, 1952. 



4. Smissman, E. E. et al. .1. Am. Chem. Soc. 



75: 2029-2031, 1953. 



5. Larson, L. M. e/ fl/. J. Am. Chem. Soc. 7.1: 



2036-2039, 1953. 



6. van Jamelen (sic), E. E. Quoted in Naka- 



nishi, K. et al. Bull. Chem. Soc. Japan 

 27:539-543, 1954. 



7. Gochnauer, M. B. and McCoy, E. J. Exptl. 



Zool. 125: 377-406, 1954. ^ 



8. van Tamelen, E. E. et al. J. Exptl. Zool. 



78: 4817-4818, 1956. 



9. Dyer, J. R. Quoted in reference 8. 



10. Horowitz, M. I. Thesis, Rutgers Univer- 



sity, 1957. 



11. Hall, H. H. and Benedict, R. G. U. S. 



Patent 2,846,310, August 5, 1958. 



Strep tolydigiii 



Produced by: Streptoniyces lydicus (2). This 

 culture also produces actithiazic acid. 



Synonym: Portamycin. 



Method of extraction: I. Broth adjustetl to pH 

 7.5 to 8.0, heated to 60°C for 10 minutes, cooled 

 to 27.4°C, filtered. A. Filtrate extracted at pH 

 7.5 to 8.0 with methylene chloride. Extract con- 

 centrated until it contains 150 mg of solids per ml, 

 then stirred with pH 4.0 citrate buffer. Addition 

 of Skellysolve B to the methylene chloride causes 

 the free acid form of streptolydigin to precipitate. 

 Precipitate leached with Skellysolve B and ace- 

 tone (3:1), and resulting solution concentrated to 

 an oil. Oil dissolved in acetone. Addition of water 

 precipitates the antibiotic. Countercurrent dis- 

 tribution indicates a biologically inactive product 

 (1, 2). B. Broth-filtrate extracted with methylene 

 dichloride at pH 3.0. Extract stirred with water at 

 pH 7.0; solvent removed by vacuum distillation. 

 Aqueous residue freeze dried. Purified by extrac- 

 tion with ethylene dichloride at pH 2.5 and con- 

 centrated in vacuo. Oily residue taken up in ethj-1 

 ether and precipitated with Skellysolve B (2). II. 

 Can also be isolated by adsorption on IRC-50 (Na+ 

 form), Dowex 1, or Permutit DR, and elution with 

 aqueous neutral or acidic alcohols (2). 



Chemical and physical properties: Strong enol 

 acid. Orthorhombic needles. Loses birefringence 

 at 110°C and melts at 144-150°C. Soluble in com- 

 mon polar organic solvents. Insoluble in water and 

 dilute mineral acids (<1 mg per ml). Ultraviolet 

 absorption spectrum maxima at 234 (El'l^ 139.1), 

 357.5 (E'i%n 590.5), and 370 m/. {E^cm 560.3), with 

 inflections at 295, 309.5, and 342 m^ (0.01 X eth- 

 anolic sulfui'ic acid); or at 261 {STem 223.6), 291 

 (El'ln, 270.7), and 336 mfj. {E\l,n 331), with an inflec- 

 tion at 302 niM (0.01 A' ethanolic KOH). Infrared 

 spectrum given in references 1 and 2. [«]„" = —64° 

 to -67° (c = 2 per cent in 0.005 A' KOH in 95 per 

 cent ethanol) ; or —93° (c = 1.6 per cent in chloro- 

 form). Positive FeCI.3 , Bro in CCU , iodoform, and 

 titanium trichloride (for enediols and enols of 

 1,3-diketones) tests. Negative bromine water, 

 Fehling (Benedict modification), Molisch, 2,6- 

 Dichlorophenol-indophenol reduction, biuret, and 

 ninhydrin tests. No free amino groups. Crystallo- 

 graphic data given in references 1 and 2. Most 

 stable at alkaline pH; less stable at pH 5.0; un- 

 stable at more acidic pH. Loses 50 per cent of 

 activity in a 50 per cent ethanolic solution at 25°C. 

 Stable for 4 months at 4°C. pKa = 5.3 (in 65 per 

 cent ethanol), or 5.7 (in 67 per cent dimethyl- 

 formamide). C.jsHjTOyN-. (2) or C32-35H46-00N2O9-10 

 (1): C = 64.29%; H = 7.68%; N = 4.70%; C— 



