DESCRIPTIONS OF ANTIBIOTICS 



327 



110°C (decomposition). Very soluble in methanol, 

 ethanol, acetone, and butanol. Soluble in dilute 

 aqueous acids and moderately soluble in water 

 and ligroin. Insoluble in hexane, carbon tetra- 

 chloride, and n-dibutyl ether. More soluble in 

 aqueous alkaline solution than erythromycin or 

 carbomycin. Ultraviolet absorption spectrum 

 maximum at 290 to 295 m/u (e = 50), a broad, low 

 intensity peak (4, 16, 18). Infrared spectnun given 

 in references 1 and 4. [a]i, = —65° =b 1° (c = 2 per 

 cent in methanol). Positive Fehling (slow) and 

 Tollen tests. Negative FeCl.s and ninhydrin tests. 

 Rf = 0.5 on paper chromatography with benzene 

 saturated with formamide. pK,.,' = 8.5. C.i.5H6i-63- 

 0,2N (12, 16): C = 61.11%; H = 8.98%; N = 2.15%. 

 Molecular weight, about 715. Equivalent weight, 

 690 (1, 16, 18). Forms a crystalline solvate with 

 chloroform, m.p. 120-122°C (decomposition) in 

 which the chloroform is tenaciously bound, as well 

 as other solvate-hydrate complexes. Methanolysis 

 of oleandomycin under mild acidic concHtions 

 gives "desoleandomycin," C2SH49NO9 , a colorless 

 substance, m.p. 116-118°C, and CsHi604 , the 

 methylglycositle of L-oleandrose (2-desoxy-L- 

 glucomethylose-3-methyl ether). Acid hydrolysis 

 products include desosamine (18). Oleandomycin 

 hydrochloride (anhydrous): m.p. 125-128°C (1) or 

 134-135°C (4). Hydrochloride (Dihydrate) : Crys- 

 talline; m.p. 134-135°C. Very soluble in water. 

 [a]o = 56.8° (c = 2 per cent in methanol). Stable in 

 aqueous solution at room temperature for several 

 hours, over a wide range of pH. Stal)le in the dry 

 state or in anhydrous solvents. Unstable to acid 

 pH on heating (4, 18). Sulfate: Long, white needles. 

 Soluble in water (4). Phosphate: Crystalline; 

 m.p. 150°C (decomposition). Water-soluble (16). 

 Oleandmycin is composed of a polyhydroxy, 

 polymethyl ketolactone ("oleandride") gly- 

 cosidically bound with the desoxy sugars L- 

 oleandrose and desosamine (3). Partial structure 

 is given in reference 16. Complete structure (21): 



OCH3 



O O 



CH3 J ] CH3 



O [ I CH3 



CH3 CH3 



Biological activity: In vitro: Active on gram- 

 positive bacteria at <0.19 to 6.25 ng per ml. In- 

 active on gram-negative bacteria, except for the 

 following: Listeria monocytogenes (3.12 /ig per ml) , 

 Neisseria (3.12 to 6.25 ^g per ml), Br. bronchi- 

 septica (7 to 25 /xg per ml), and H. influenzae (0.078 

 Mg per ml) (1,4). Not active on C. albicans. Activ- 

 ity diminished by serum and urine (7). Synergistic 

 action with tetracycline on certain gram-positive 

 organisms in vitro and in vivo (6). Cross-resistance 

 with erythromycin, spiramycin, carbomycin, and 

 streptogramin (5). In vivo: Active on Leptospira 

 iclerohaemor rhagiae infections (hamsters) (14) ; 

 Streptococcus hemolyticus, D. pneumoniae, Staph. 

 aureus, FJntero<-occus, Sal. typhimurium (mice), 

 Rickettsia rickettsii (eggs) and other rickettsiae, 

 as well as psittacosis (eggs, mice) and other intra- 

 cellular parasites (1, 4, 9). Active on certain 

 protozoa (1). Active, at high doses, on tuberculosis 

 and syphilis (7, 8). Not active on trypanosomiasis, 

 trichophytosis (8), Rickettsia akari, SK enceph- 

 alomyelitis, or influenza A viruses (9). Stimulates 

 growth of chicks (15) and turkey poults (17). 



Toxicity: Hydrochloride: LD50 (mice) 460 to 600 

 mg per kg intravenously, about 4 gm per kg by 

 gavage, 8.2 gm per kg orally, and 2.5 gm per kg 

 subcutaneously (8, 13). LI).^n (rat) 376 ± 5 mg per 

 kg (12) or 550 mg per kg (1) intravenously, 10.0 

 gm per kg subcutaneously, and >10.0 gm per kg 

 orally (8). Toxicity to hamsters increased over a 

 a period of H^ years from the time the drug was 

 introduced into the laboratory (14). Highest con- 

 centration permitting migration of epithelial cells 

 in tissue culture is 20 mg per ml (20). 



Utilization: Used in infections caused by gram- 

 positive organisms and antibiotic-resistant 

 staphylococci (2,9-11). Used in combination with 

 other antiliiotics (6). 



TridccI yhilcaiuhnuyci n 



Produced by: Acylation of oleandomycin. 



Chemical and physical properties: C41H67NO3 . 

 Insoluble in distilled water and buffered aqvieous 

 solutions (pH 4 to 7). Ultraviolet spectrum like 

 that of oleandomycin. Can be separated from 

 parent compound by paper chromatography 

 (formamide-saturated benzene) (16). 



Biological activity: Has about one third the 

 activity of oleandomycin on Sarcina lutea. (Jives 

 higher blood levels in human Iteings than oleando- 

 mycin (16) . 



Toxicity: Well tolerated by human beings (19). 



References : 



1. Sobin, B. A. et al. Antibiotics Ann. 827- 



830, 1954-1955. 



2. Ross, S. Antibiotics Ann. 600-603, 1955- 



1956. 



