DESCRIPTIONS OF ANTIBIOTICS 



283 



at an alkaline pH l)y most organic solvents (ben- 

 zene, chloroform, ether, amyl acetate, and tolu- 

 ene). Back-extraction in water at pH 2.0. After 

 two or three purifications in this manner, concen- 

 tration of organic solvent solution permits crystal- 

 lization (1, 3). 



Chemical and physical properties: Macrolide, 

 containing desosamine. White plate crystals, hav- 

 ing a bitter taste; m.p. 76-80°C (1) or 70-75°C (3). 

 Very soluble in most organic solvents, but only 

 slightly soluble in water. Infrared data given in 

 reference 3. [a^i^ = +32° (c = 1 per cent in CHCLi) 

 (1), or [a]o = -7.0° (CHCl:i) (3). Stable at room 

 temperature between pH 2 and 9, but rapidly 

 destroyed at 100°C. C28H48NO8 . Molecular weight, 

 530. Hydrochloride: m.p. 120°C. Very soluble in 

 water, ethanol, methanol, and chloroform. Poorly 

 soluble in other organic solvents. Precii)itated 

 from aqueous solutions by picric acid and Rei- 

 necke salt (1, 3, 6). Criseomycin reacts with 

 methyl iodide to form a ((uaternary salt: C29H51- 

 NOsI, m.p. 193-195°C. [«]„ = +31.0° (ethanol). 

 This salt has the same formula, melting point, and 

 infrared spectrum as the picromycin quaternary 

 salt formed with methyl iodide, but differs in rota- 

 tion (5). 



Biological activity: Active mainly against gram- 

 positive bacteria, including mycobacteria. Active 

 against Neisseria. Inactive against most gram- 

 negative bacteria and C. albicans. Cross-resistance 

 in vitro between carbomycin, erythromycin, and 

 griseomycin. Not inactivated in vitro by human 

 serum or whole blood (1). Destroyed in the liver 

 (-t). 



To.ririty: LDoo (mice) 1330 mg per kg subcutane- 

 ously, 210 mg per kg intraperitoneally. Orally, 2100 

 mg per kg is not toxic, (iriseomycin is absorbed 

 by the gastrointestinal wall (1). Nontoxic to 

 rabbits when applied cortically {()). 



References: 



1 . Van Dijck, P. J. et al. Antibiotics & ('hemo- 



therapy 3: 1243-1240, 1953. 



2. DeSomer, P. et al. Resumes Communs. Oth 



Intern. Congr. Microbiol. 1: 161, 240, 1953. 



3. Belgian Patent 522,647, September 30, 1953. 



4. DeSomer, P. et al. Antibiotics & Chemo- 



therapy 4: 546-550, 1954. 



5. Vanderhaeghe, H. Cited in reference 4. 



6. DeSomer, P. Giorn. microbiol. 2: 216-232, 



1956. 



Griseoviridin 



Produced by: Streptomyres griseus and S. griseo- 

 viridus (1, 5). These same strains also produce 

 etamycin (viridogrisein) (1). 



Method of extraction: Culture-broth adjusted to 

 pH 4.4 and filtered on Hyflo Super-Cel. Extraction 

 of the filtrate at pH 7.2 with 0.5 volume of ethylene 

 dichloride. Concentration of the extract in vacuo 

 yields a precipitate of crude griseoviridin, which 

 is added to boiling absolute methanol and filtered 

 on paper. To the filtrate, Nuchar C190N is added; 

 after refiuxing for 5 minutes, the suspension is 

 filtered through paper. Crystallization is allowed 

 to proceed by storing the filtrate at 8°C. The 

 crystals are washed with cold absolute methanol 

 and dried in vacuo (1). Crvstallized from pvridine 

 (2). 



Chemical and physical properties: Neutral sub- 

 stance. Griseoviridin base: Plate crystals; m.p. 228- 

 230°C. Soluble in pyridine; moderately soluble in 

 lower alcohols; sparingly soluble in water and 

 nonpolar solvents. Ultraviolet absorption spec- 

 trvnii maximum at 220.5 ni/j (e = 44,000) and an 

 inflection at 277.5 mju (e = 1500). Infrared data 

 given in reference 2. [a]" = —237° (c = 0.5 per 

 cent in methanol). Contains no thiol, methoxyl, or 

 methylimino groups. Positive Baeyers and chro- 

 mate-nitric acid tests. Negative FeCh , Folin- 

 Ciocalteau, Sakaguchi, and Jacobs-Hoffman tests. 

 Acid hydrolysis products include cysteine, serine, 

 and an unidentified ninhydrin-positive substance 

 (3). C2.2H.>9()7N,S : C = 54.9%; H = 5.8%; O = 

 24.4%; N = 8.7%; S = 6.2%. Molecular weight, 

 485 to 490 (1-3). Griseoviridin crystallizes from 

 methanol in two different forms, depending on the 

 temperature of the solvent dtu-ing crystallization. 

 Form A (a hemimethanolate) is obtained at 

 >30°C; form B at <30°C. B loses solvent in air to 

 give A. Form A: Large crystals; m.p. 160°C. 

 [aJu = —237° (c = 0.5 per cent in methanol). 

 Crystallographic data given in reference 2. Reac- 

 tion product with HCl: Needles; m.p. about 180°C 

 (decomposition) (3). Partial structure of griseo- 

 viridin (4) : 



CHs 



N— C— S— CH,— CH— C— 



/ I I 



_C=0 N 



/ \ 



o 



\ II 



N— CHo— [C5(OH)]— CH— C=CH— C— 



/ I I 



OH O O 



I I II 



CH.,CHCH2CH=CHC— 



Biological activity: Active in vitro against a 

 variety of gram positive and gram-negative Ijac- 

 teria and actinomycetes at a level of 0.1 to 10 yug 



