286 



DESCRIPTIONS OF ANTIBIOTICS 



to pH 6 to 7, calcium precipitated as the oxalate, 

 and the whole filtered. Filtrate adsorbed on IRC- 

 50 (Na+ phase), eluted with 1 ,V H0SO4 , and pre- 

 cipitated as the pentachlorophenol derivative. 

 Purified by conversion to the sulfate, followed by 

 fractional crystallization from an aciueous metha- 

 nolic solution of the /^-(/>'-hydroxyphenylazo)ben- 

 zene sulfonate (2). 



Chemical and physical properties: Basic amino 

 polysaccharide. Base: White amorphous powtier. 

 Soluble in water and methanol. Insoluble in com- 

 mon organic solvents. [a]f = -|-63° ± 2° (c = 1 

 per cent in water). C20H47O15X5 . Molecular 

 weight, 610 (2, 3). Methanolysis in the presence of 

 HCl gives a product which was termed "pseudo- 

 neamine," CisHooOtN.-j , composed of 1,3-diamino- 

 4,5,6-trihydroxycyclohexane (meso) (also present 

 in neomycin and kanamycin) and D-glucosamine. 

 Two possible structures for pseudoneamine were 

 proposed : 



OH 



NH, H 



H / \ OH 

 H OH\ 



NHo H 



H 



CH.OH 



H 



H 



H 



H (). 



H \ 

 H OH/ 



OH 



NHo H 



Sulfate: White amorphous powder. No charac- 

 teristic infrared or ultraviolet al)sorption spec- 

 trum, [a if," = -f 50-52° (c = 1 i)er cent in water) 

 and does not vary with pH. Rf = 0.4(1 on paper 

 chromatography (methanol 2 i)or cent aqueous 

 NaC'l, 2:1), paper impregnated with NaHSOj at 

 pH 2.4. Positive ninhydrin, diazo p-nitroaniline 

 (for primary amino groups), and periodic acid 

 tests. Negative nitroi)russide (secondary amino 

 groups), Fehling, Sakaguchi, Pauly, and I'llson- 

 Morgan tests. Furfural formed on treatment with 



acid. Total N = ().2%; N (Van Slyke) = G.0%; N 

 (Sorensen) = 3%. p-(p' -Hydroxy phenylazobenzene 

 sulfonate: Orange crystals; m.p. 220°C (decom- 

 position). Thermostable from ])H 2 to 10. la]f:' = 

 +37° (c = 0.5 per cent in methanol) (2). N -Benzoyl 

 hydroxymycin: White needles; m.p. 232°C (decom- 

 position). [a\f = +36° ± 2° (c = 0.3 per cent in 

 methanol). Biologically inactive (2). 



Biological activity: Active on gram-negative and 

 gram-positive bacteria and mycobacteria. Active 

 on Endamoeba histolytica at 5 to 10 jug per ml (2). 

 Weak activity in vitro on Trichomonas vaginalis 

 (1). Not affected by serum or glucose. Active on 

 mycobacteria resistant to streptomycin. Active in 

 mice on infections caused by Staph, aureus, Diplo- 

 coccus mucosus, K. pneumoniae, Sal. typhosa, E. 

 coli, and Ps. aeruginosa. Less active on D. pneu- 

 moniae and Streptococcus hemolyticus infections. 

 As active as streptomycin on tuberculosis in mice 

 and guinea pigs (2). Active in mice on T. vaginalis 

 (1). No antiviral activity in vivo. 



Toxicity: LD50 (mice) 125 ± 5 mg per kg intra- 

 venously, 1020 =h 110 mg per kg subcutaneously. 

 Does not have neon\ycin-like toxicity (2). 



References : 



1. Vaisman, A. and Hamelin, A. Comjjf. rend. 



247: l(i3-165, 1958. 



2. Hagemann, (.J. et al . Ann. pharm. frang. 16: 



585-596, 1958. 



3. Bartos, M. J. Ann. pharm. frang. 16: 596- 



600, 1958. 



4. Schaffner, C. P. Personal communication. 



Hy tli'oxyst rep toni vein 



Produced by: Streptoini/ccs rubrireticuli (formerly 

 referred to as S. rcticuli) (1, 11). This strain also 

 produces rotaventin. S. griseocarneus (2, 3, 5, 6, 8). 

 These strains also produce an antifungal substance 

 in low yield (9). Streptoniyces sp. This strain differs 

 from the above, but belongs to the reticuli group 

 (12). 



Synony}ns: Reticulin (1, 10), antil)iotic NA 232- 

 Ml (2). 



Method of extraction: I. See I under strepto- 

 mycin. II. Culture-broth acidified, filtered, neu- 

 tralized, and adsorbed on IRC-50. Eluted with 0.5 

 A'^ H2SO4 . Eluate neutralized, concentrated, and 

 acetone added to give the crude substance. Puri- 

 fied by chromatography on Darco G-60-Celite 545 

 (2). 



Chcniical and physical properties: Differ?, from 

 streptomycin by one oxygen atom present as a 

 hydroxyl group on the methyl group of the strep- 

 tose moiety (2) (see Chapter 6). Solul)lo in water, 

 ethanol, and dilute acids (9). [a]„ = -790° (2). 



