282 



DKSCRII'TIOXS OF ANTIBIOTICS 



transferred 1o the solvent. Solvent conoent rated 

 in vacuo. A is purified by countercurrent distribu- 

 tion (ethyl acetate-phosphate buffer, pH 5.8). 

 Crystallized from ethyl acetate. Recrystallized 

 from methanol (6). 



Chemical and physical properties: Orange-yellow 

 needles; m.p. 194-197°C (decomposition). Ultra- 

 violet absorption spectrum maxima at 265 m^u 

 (£'}L 1980) and 362 m^ (E^L 330) (methanol). 

 Infrared spectrum given in reference 6. CnHu- 

 O6N2 : C = 59.51%; H = 4.36%; N = 8.02%; 

 O — CH3 = 7.3%. Insolul:>le in water, ether, and 

 benzene. Slightly soluble in ethyl acetate and 

 ethanol. Soluble, but destroyed, at alkaline reac- 

 tion. More stable at pH 2.0 than 7.0. Monomethijl 

 ester of A: Yellow crystals; m.p. 149°C. The struc- 

 ture of griseolutein A, l-methoxy-4-[(hydroxy- 

 acetoxy)methyl]-9-carboxyphenazine (6, 7), is 

 given in Chapter 6. 



Biological activity: Active on gram-positive and 

 gram-negative bacteria (1). Activity affected by 

 cysteine and serum, Init not by cystine. More 

 active at acid than alkaline pH (2, 4). 



Toxicity: >2 gm per kg or >500 mg per kg are 

 not to.xie to mice subcutaneously (2, 4). 



References: 



1. Umezawa, H. et al. J. Antibiotics (Japan) 



4: 34-40, 1951. 



2. Ogata, Y. J. Antibiotics (Japan) 4: 213- 



218, 1951. 



3. Okami, Y. J. Antibiotics (Japan) 5: 477- 



480, 1952. 



4. Ogato, T. et al. J. Antibiotics (Jai)an) 7A : 



15-16, 1954. 



5. Nakamura, S. et al. J. Antibiotics (Japan) 



lOA: 265-266, 1957. 



6. Nakamura, S. et al. J. Antibiotics (Japan) 



12A: 55-58, 1959. 



7. Yagishita, K. J. Antibiotics (Japan) 13A: 



83-96, 1960. 



Griseoluleiii li 



Produced by: A mutant of the Streptomyces 

 griseoluteus culture that produces griseolutein A. 



Method of extraction: Broth-filtrate extracted 

 with butyl acetate at pH 2.0. Extract concen- 

 trated in vacuo to precipitate griseolutein B. Crude 

 powder dissolved in dioxane, then concentrated 

 to give crystalline substance (2, 4). Puritted by 

 countercurrent distribution between pH 5.8 phos- 

 phate buffer and ethyl acetate. Acidification of 

 active fractions gives crystals. Recrystallized 

 from pyridine-dioxane-ether (7). 



Chemical and physical properties: Contains a 

 phenazine nucleus (6). Yellow prisms. Browns at 



al)out 160°C, darkens at 180°C, and chars at 220°C. 

 Solul)le in aciueous NaHCO.'s and pyridine. Spar- 

 ingly soluble in dioxane and methyl ethyl ketone. 

 Insoluble in toluene, ether, and butyl acetate. 

 Ultraviolet absorption spectrum maxima at 281 to 

 283 niM (EiL 296) and 342 to 344 niyu (J5}L 170) 

 (methanol). Infrared absorption spectrum given 

 in reference 1. [a\',i' = —6° (c = 0.7 per cent in 

 pyridine) (7). Infrared spectrum given in reference 

 4. Unstable in aciueous solution. C47HibObN2 (3). 

 The structure of griseolutein B (l-methoxy-4(a,/3- 

 dihydroxyethoxymeth3'l)phenazine - 9 - carboxylic 

 acid) (8-10) is given in Chapter 6. Diacetyl griseo- 

 lutein B: Light yellow prisms (7). Alkaline hy- 

 drolysis of this derivative gives griseoluteic acid 

 (7)." 



Biological activity: Active on gram-positive and 

 gram-negative bacteria, mycobacteria, and pro- 

 tozoa (2, 3, 5). Antirickettsial activity (3). Only 

 slight cross-resistance between A and B. Active 

 in mice on Staph, aureus infections (2). Active on 

 Ehrlich carcinoma in mice (5). B has weaker anti- 

 bacterial activity than A, especially against Pr. 

 vulgaris (4). Diacetyl griseolutein B is biologically 

 active (8). 



References: 



1. Yagishita, K. et al. J. Antibiotics (Japan) 



6A: 113-116, 1953. 



2. Ogata, Y. et al. J. Antibiotics (Japan) 



6A: 139, 1953. 



3. Ogata, Y. Japan. J. Med. Sci. & Biol. 6: 



493-501, 1953. 



4. Osato, T. et al. J. Antibiotics (Japan) 



7A: 15-16, 1954. 



5. Umezawa, H. Giorn. microbiol. 2: 160- 



193, 1956. 



6. Nakamura, S. et al . J. Antibiotics (Japan) 



lOA: 265-266, 1957. 



7. Nakamura, S. Chem. Pharm. Bull. 6:539- 



543, 1958. 



8. Nakamura, S. Chem. Pharm. Bull. 6: 



547-550, 1958. 



9. Nakamura, S. J. Antibiotics (Japan) 12A: 



26-27, 1959. 

 10. Yagashita, K. J. Antibiotics (Japan) 13A: 

 83-96, 1960. 



Griseoiiiyciii 



Produced by: Streptomyces griseohis (1, 3). 



Synonyms: Griseomycin is similar or identical 

 to proactinomycin B, and is isomeric with picro- 

 mycin (6). Related to amaromycin (1) andlomycin 

 (2"). 



Method of extraction: Whole culture acidified to 

 pH 2.0 and hltered. Broth-iiltrate can be extracted 



