236 



DESCRIPTIOXS OF ANTIBIOTICS 



(c = 0.3 per cent in glacial HAc). Gives yellow- 

 green color in alcoholic FeCls (6) and dark green 

 in FeCla and dimethjdformamide. Chartrexisin di- 

 hydrate: Yellow rhombic plates, m.p. 234-235°C 

 (crystallized from acetonitrile) (9); or greenish 

 yellow crystals, m.p. 180°C. Fluoresces in ultra- 

 violet light. Stable for several hours at pH 2 to 10 

 at 22°C (1). Pentabenzoate: m.p. 204-206°C (formed 

 with benzoyl chloride in i)yridine) (6). Penta- 

 acetyl derivative: m.p. 270°C. Alkali-insoluble (6). 

 Chartreusin decomposes both by heating to 250°C 

 and by acid hydrolysis to give a weakly acidic 

 aglycone, C19H10-12O6 . Acid hydrolysis products 

 also include D-fuco.se and D-digitalose. Aglycone: 

 Yellow needles, subliming at 260°C (crystallized 

 from toluene or pyridine) or m.p. 310-311 °C (6, 

 9). Soluble in aqueous alkali, but not in common 

 organic solvents. Negative flavonol test (9). Char- 

 treusin is believed to be a derivative of 2-phenyl- 

 naphthalene or 2,3-benzofluorene, containing a 

 lactone group, two phenolic hydroxyls, and two 

 o.xygens of undetermined nature. There is an ad- 

 ditional methyl or methylene group present, and 

 one of the phenolic groups is glycosidically bound 

 to a disaccharide chain composed of I)-fucose and 

 l)-digitalose (10). C = 59.49, 59.09, 59.89, or 

 59.71%; H = 5.43, 5.30, 5.19, or 5.26% (1, 2, 6, 9). 

 C32H34-36O14 (6, 9, 10) or CisHisOs (1, 2, 4). 



Biological activity: Active in vitro on gram-posi- 

 tive bacteria and mycobacteria. Active on certain 

 gram-negative bacteria (Neisseria andHeniophilus). 

 Active on Xocardia asteroides, various Strepto- 

 niyces spp., and Actinomyces bovis. Active on vari- 

 ous bacteriophages. Slightly active (10 to 40 /zg 

 per ml) on influenza A(FM-l), influenza B (Lee), 

 HVJ (hemagglutinating virus of Japan or Sendai 

 virus) in contact tests. Active in tissue culture on 

 influenza PR 8. Not active on fungi or Tricho- 

 monas (1, 3, 7-9, 11). Not active in vivo on Strep- 

 tococcus hemolyticus, pneumococcus type I, Sal. 

 schottmuelleri, M. tuberculosis, C . albicans, Histo- 

 plasma capsulatuni , Trypanosoma equiperdum , 

 Endamoeba histolytica, Syphacia obvelata, influ- 

 enza A or SK viruses, or sarcoma 180 (9). 



Toxicity: Chartreusin: LDn (mice) 2500 mg per 

 kg subcutaneously (1). Xn chartreusin: LDso 

 (mice) 250 to 300 mg per kg intravenously (1-3). 

 Said to have a cumulative toxicity (1). 



References : 



1. Leach, B. Fj. et cd. J. Am. Chem. Soc. 75: 



4011-4012, 1953. 



2. Ishii, Y. et al. J. Antil)iotics (Japan) 8A: 



96-99, 1955. 



3. Ghoine, M. and Zavaglio, V. Giorn. micro- 



V)iol. 1: 176-184, 1955. 



4. Grein, A. et al. Giorn. microbiol. 1: 310- 



315, 1955. 



5. Shibata, M. et al. Ann. Kept. Takeda Re- 



search Lab. 15: 45-48, 1956. 



6. Arcamone, F. et al. Antibiotics & Chemo- 



therapy 6: 283-285, 1956. 



7. Calhoun, K. M. and Johnson, L. E. Anti- 



biotics & Chemotherapy 6: 294-298, 1956. 



8. Miyakawa, T. Virus 7: 394-399, 463, 1957. 



9. Berger, J. et al. J. Am. Chem. Soc. 80: 



1636-1638, 1958. 



10. Sternbach, L. H. et al. J. Am. Chem. Soc. 



80: 1639-1647, 1958. 



11. Anzai, O. Virus 8: 174-181, 1958. 



Chloramphenicol 



Produced by: Streptomyces venezuelae (5, 26). 

 Also produced by S. phaeochromogenes var. chloro- 

 myceticus (0, 10), »S. omiyaensis (10), Streptomyces 

 sp. (22, 71), and by chemical synthesis (16). 



Synonyms: Chloromycetin; sintomicetin; levo- 

 mycetin; synthomycin; antibiotic 8-44. 



Method of extraction: lA. Acidified liroth-fil- 

 trate extracted with ethyl acetate, amyl acetate, 

 cyclohexanone, butanol, or methyl isobutyl ke- 

 tone. Extract solvent distilled off in vacuo. Resi- 

 due e.xtracted into diethyl ether or nitromethane. 

 Chromatographed in aluminum oxide. Solvent in 

 active fractions evaporated off; residue taken up 

 in water and washed with petroleum ether. Con- 

 centration of aciueous solution gives crystals. 

 Recrystallized from methylene dichloride, ethyl- 

 ene dichloride, and diethyl ether petroleimi ether 

 (1, 8, 17). IB. Broth-filtrate extracted with ethyl 

 acetate at pH 8.5 to 9.0. Extracts concentrated, 

 kerosene added, and the whole washed with 0.01 

 A^ H0SO4 , 5 per cent NaHCOs , and distilled water. 

 Solvent dried, then distilled off in vacuo at 37°C. 

 Cooling yields crystals (8). II. Broth-filtrate 

 extracted with ether. Extract evaporated to dry- 

 ness. Residue washed with hot benzene, leaving 

 crystals. Recrystallized from benzene-methanol. 

 Purified by chromatography on alumina from 30 

 per cent methanol in CHCI3 . Eluate concentrated 

 to dryness. Residue crystallized from chloroform-5 

 per cent methanol (3). III. Adsorbed from broth- 

 filtrate at pH 5.6 on activated carbon. Eluted with 

 acidic acetone. Eluate adjusted to pH 4.0 to 5.0 

 and solvent distilled off in vacuo. Taken up in 

 ether. Ether dried, concentrated, decolorized, 

 and evaporated to dryness. Residue taken up in 

 hot water. Antibiotic crystallizes out on drying 

 (17,22). 



Chemical and physical properties: Neutral sub- 

 stance (1). Free base: Colorless needles or elon- 



