328 



DESCRIPTIONS OF ANTIBIOTICS 



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Chem. Soc. 15N, 1956. 



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Med. 93:388-393,1956. 



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7. P\ist, B. et al. Schweiz. med. Wochschr. 



86: 1245-1246, 1956. 



8. Fust, B. et al. Helv. Med. Acta 23: 714- 



741, 1956. 



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1956. 



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Ann. 44-47, 1956-1957. 



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Med. 4: 703-707, 1957. 



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58, 1957. 



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Chemotherapy 7:419-424, 1957. 



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256-258, 1957-1958. 



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Oligoniycins 



Frudueed by: Streptomyees sj). resembling S. 

 diastatoehromogenes (1), and Streptomyees sp. (7). 



Synonym: The originally described oligomycin 

 contained mostly oligomycin A (10). 



Remarks: All the antibiotic activity could be 

 retained in the mycelium if the pH of the culture 

 were controlled (7). 



Method of extraetion: I. Broth clarified with 

 Celite 535 and adjusted to pH 2.0 with HCl. 

 Precipitate which forms extracted with ethyl 

 acetate. Extract decolorized with Darco G-60, and 

 distilled off in vacuo. Residue treated with Skelly- 

 solve A and ground to a brown powder. Crystal- 

 lized from glacial acetic acid-cold distilled water, 

 then from ethanol -water. P\u-ification and separa- 



tion of the components by chromatography on 

 Celite 545 pretreated with the acpieous phase of 

 Skellysolve B - dioxane -ethanol - water mixture 

 (200:72:26:18.5) and developed with the organic 

 phase, giving comjjonents C, A, and B, in that 

 order (11). Component A-eontaining fractions: 

 Evaporated and cooled to give a semisolid product . 

 To an ether solution of this, Skellysolve B is added 

 to incipient precipitation. Crystallized on stand- 

 ing to give Form I of A (Al); m.p. 139-141°C. 

 Slow crystallization from ether-Skellysolve B 

 mixtures or dilute acetic acid solutions gives Form 

 II (All); m.p. 150-151°C (decomposition). Re- 

 crystallization of All from acetone-methanol 

 gives Al. Component B: Recrystallized from 

 methanol to give Form I (BI) ; m.p. 160-161°C. BI 

 changed to BII, m.p. 169-170°C, on standing at 

 room temperature for several months. Recrystal- 

 lization of BII from methanol gives BI. Compo- 

 nent C: Crystallized from ether-petroleum ether 

 (1:1) (7). 



('he)nical and physical properties: Complex con- 

 taining three components. A, B, and C. Neutral 

 unsaturated alcohols possibly containing ketone 

 groups. Complex: Colorless hexagonal crystals; 

 m.p. 135. 8-136. 3°C. Soluble in most common or- 

 ganic solvents but not in petroleum ether, cyclo- 

 hexane, or water. [a]'n' = —51° (c = 3 per cent in 

 methanol) (1). Oligomycin A: Exists in two crys- 

 talline forms, Al and All (see "Method of Extrac- 

 tion"). Al: Long needles; m.p. 140-141°C. All: 

 hexagonal crystals; m.p. 150-151 °C (decomposi- 

 tion). Both very soluble in acetone, soluble in 

 ethanol, ether, aiul glacial acetic acid; scarcely 

 soluble in benzene; insoluble in water and Skelly- 

 solve B. [a]t' = 54.5° (c = 4.4 per cent in dioxane) 

 (All). Al: C = (J7.76%; H = 9.51%; O = 22.30%; 

 C— CH;i = 16.4%; C24H40O6 . Diacetate: m.p. 112- 

 113°C. [a]V = -86.1° (c = 1.74 per cent in ethanol). 

 Oligomycin B: Two crystalline forms, BI and BII 

 (see "Method of Extraction"). BI: Platelets; 

 m.p. 160-161°C. [«1;'" = 49.5° (c = 1.03 per cent 

 in methanol). C = 66.60%,; H = 9.07%,; O = 

 2.40%; C— CH, = 18.9%. CssH.ieOe. BII: m.p. 

 169-170°C. Both very soluble in acetone; soluble in 

 benzene and ether; scarcely soluble in ethanol and 

 glacial acetic acid; insoluble in water and Skelly- 

 solve B. Diacetate: m.p. 135.5-136.5°C. [a]'p = 

 —66.6° (c = 0.63 per cent in dioxane). Oligomycin 

 C: Rod-shaped crystals; m.p. 198-200°C. Very 

 soluble in acetone and glacial acetic acid; soluble 

 in ethanol and ether; scarcely soluble in benzene; 

 insoluble in water and Skellysolve B. [a];,' = 

 -80.7° (c = 3.70 per cent in cUoxane). C = 69.9%; 

 C— CH;, = 19.3%. C-inHjeOe .A,B, and C: All have 



