DESCRIPTIONS OF ANTIBIOTICS 



401 



Method of extraction: Powdered mycelium ex- 

 tracted in a Soxhlet apparatus with petroleum 

 ether for 5 days, ether, acetone (2 days each), and 

 80 per cent methanol (5 days), in succession. Pe- 

 troleum ether extract evaporated. Valinomycin 

 precipitates slowly from the residual oil. Precipi- 

 tate is fractionally crystallized from n-dibutyl 

 ether. Some additional valinomycin is obtained 

 from the methanolic extracts (1). 



Chemical and physical properties: Polypeptide. 

 Colorless rectangular plates; m.p. 190°C. Does 

 not sublime at low absolute pressure. Readily 

 soluble in common organic solvents; practically 

 insoluble in water, 2 N HCl, and 2 A' aqueous 

 alkali. Xmax'"'''"^ 281 m^- Infrared spectrum given in 

 reference 3. [a]l° = -|-31.0° (c = l.G per cent in 

 iienzene). No color in concentrated H2SO4 . Nega- 

 tive ninhydrin test. C = 58.34%; H = 8.25'^r; 

 N = 7.48%; C.36H6oOi2N4 . Hydrolysis products 

 include D- and L-valine, lactic acid, and a-hy- 

 droxyisovaleric acid. Structural formula (2, 4): 



3. Brockmann, H. and Schmidt -Kastner, G. 



German Patent 926,806, April, 1955. 



4. Brockmann, H. and Geeren, H. Ann. Chem. 



Liebigs 603:216-231,1957. 



5. Schmidt -Kastner, G. Personal communica- 



tion. January 19, 1959. 



Vancomycin 



Produced by: Streptomyces orientalis (3). Cer- 

 tain strains produce one or more antibacterial sub- 

 stances other than vancomycin (9). 



Synonym: Similar to ristocetin. 



Method of extraction: I. Adsorbed at pH 7 to 

 8 from broth-filtrate on Permutit DR (0H~ phase). 

 Eluted with 1 per cent glacial acetic acid in 30 per 

 cent ethanol or acetone. Eluate concentrated in 

 vacuo, and aqueous residue adsorbed on carbon at 

 pH 5 to 7. Eluted with 50 per cent aqueous ethanol 

 at pH 2.0 (sulfuric acid). Eluate concentrated in 

 racuo, with Ba(OH)o added to maintain pH at 

 >2.5. Precipitated as the picrate, then converted 



W,C 



cV^^ W o / 



G^ 



He- 





/ 



/ 



CH, 



~CH 

 NH 



\ 



O 

 HN 



X 



^^O 



^ 



.^. 



CH. 



:^^ r?^ 



G^ 



/ 



\ 



-CH 



\ C: 



/ 



/ // 

 / ^ c 



" H\ 

 OH., 



\ 



CH. 



C " ^ r^C 



^^ ,0 







CH, 



Biological activity: Active on the following or- 

 ganisms (minimal inhibitory concentration): 

 Staph, aureus (1:30,000), B. subtilis (1:20,000), 

 .1/. tuberculosis (human, virulent) (1:900,000). 

 Active in vivo on Trypanosoma brucei (mice) at 

 half the maximal tolerated dose (2, 3). 



References: 



1. Lindenbein, W. Arch. Mikrobiol. IT: 3(51- 



383, 1952. 



2. Brockmann, H. and Schmidt-Kastner, G. 



Chem. Ber. 88: 57-01, 1955. 



to the hydrochloride; precipitated from ethanol 

 by ether or acetone, or by concentration to dryness 

 in vacuo. Purified by (a) passing through a mixed 

 IR-120 (H+ form)-IR45 (OH- form) column. Efflu- 

 ent concentrated to give free base. Or (b) neutra- 

 lizing a 20 per cent methanolic solution of the 

 hydrochloride with 10 per cent NaOH to pH 8.0 

 at 25°C to give the free base (1,9). II. Co-precipi- 

 tated or adsorbed from broth on divalent metal 

 hydroxides generated in situ as follows: 1 per cent 

 ZnS04 added to broth filtrate, and pH adjusted 



