DESCRIPTIONS OF ANTIBIOTICS 



267 



tatively from sohitions of ethanolic ;iimnonia as 

 the ammonium salt, leaving almost all impurities 

 in solution. This colorless, crystalline salt is un- 

 stable in the dry state and decomposes to the 

 pure antibiotic in vacuo (10). 



Chemical and physical properties: Macrocyclic 

 peptide lactone, containing eight amino acids. 

 Weakly basic (1) or amphoteric (3). Base: Color- 

 less amorphous powder (10). Soluble in lower alco- 

 hols and ketone, benzene, chloroform, carbon 

 tetrachloride, carbon disulfide, ethyl acetate, 

 ether, 1 .V HCl, and 1 X NaOH. Slightly soluble 

 in water. Insoluble in petroleum ether (1, 9). 

 \^l° 350 (E\7n. 71) with a shoulder at 303 (^I?,„ 34) 

 (3). [a]f = +7.7° (c = 2 per cent in methanol) (1). 

 Positive tests for an active methylene group, pep- 

 tide bond, ester, and amide groupings (hydroxamic 

 acid test). Brownish red color with F'eCh test. 

 Weakly positive Folin-Ciocalteau and Bayer tests. 

 Negative ninhydrin and Sakaguchi tests (1, 3). 

 pKa' = 7.4 (10 per cent acjueous ethanol). Stable 

 at acid pH and neutrality; inactivated by alkali. 

 Esterihcation destroys microbiological activity. 

 Calculated formula: C44H620„N8-H20: C = 

 59.0%; H = 7.05%; N = 12.3%; N— Me = 5.35%. 

 Molecular weight, 800 to 900. Proposed structure 

 (9): 



OH 



negative bacteria and C. albicans. Active in vivo 

 against experiniental D. pneumomae and Staph, 

 aureus infections in mice and E. histolytica in- 

 fections in rats and dogs. Some antirickettsial 

 activity; no antiviral activity. Active against 

 bovine mastitis, infectious bronchitis of chicks, 

 and panleukemia of cats (1. 4, 6). Active in ovo 

 on pleuropneumonia-like organisms (avian) (7). 

 Intermediate activity on sarcoma 180 in mice (8). 



Toxicity: LD50 (mice) 273.5 mg per kg intra- 

 peritoneally, >2000 mg per kg subcutaneously, 

 >3000 mg per kg orally. Etamycin produces a 

 reversible leukopenia in dogs (1). At certain con- 

 centrations, given orally or subcutaneously to 

 mice, nonedematous weight gain without increased 

 food intake was noted (4). 



References: 



1. Heinemann, B. et al. Antibiotics 



728-744, 1954-1955. 



2. Bartz, Q. R. et al. Antibiotics Ann. 



783, 1954-1955. 



3. Haskell, T. H. et al. Antibiotics 



784-789, 1954-1955. 



4. Ehrlich, J.e/oL AntiVnotics Ann. 790-805, 



1954-1955. 



5. Anderson, L. E. et al. Antibiotics & Chem- 



otherapy 6: 100-115, 1956. 



Ann. 

 777- 

 Ann. 



i5-hy(lr(ixypir()lii lie acid 



H3C 



-Ml 







O I CH— C XH 



L-Threiminc^ ,.,^ ^,j^ 



O 



l.euciue 



L-d-l'hcnvlsa: 



c=o 



1 



CH— X— C— CH— NH— C 



! I 



CH, CH3 



L-.\laniiu' 



Sarcosine 



L-^ , X-l)iiiiethylleuciiie 



Hydrochloride: m.p. 163-170°C (decomposition). 

 Soluble in methanol, ethanol, formamide, and in 

 water to the extent of 4 mg per ml. Slightly sol- 

 uble in acetone, ethyl acetate, and less polar sol- 

 vents. X*'mSc"304 {E\'^^86) with strong end-absorp- 

 tion at <250 (1). 



Biological activity: Active in vitro against gram- 

 positive bacteria, including Clostridia, at a con- 

 centration of 0.04 to 2.5 fj.g per ml. Active on 

 Endanioeba histolytica. Inactive against mostgram- 



6. Thompson, P. E. et al. Antibiotics & 



Chemotherapy 6: 337-350, 1956. 



7. Yamamoto, R. and Adler, H. E. Am. J. 



Vet. Research 17: 538-542, 1956. 



8. Field, J. B. et al. Cancer Research 18: 



(Suppl. 1) 503, 1958. 



9. Sheehan, J. C. et at. J. Am. Chem. Soc. 



80: 3349-3355, 1958. 

 10. Arnold, R. B. et al. J. Chem. Soc. 4466- 

 4470, 1958. 



