2<)0 



DESCRIPTIONS OF ANTIBIOTICS 



l-sorhodoiii veins 



Produced by: Streptnnii/ces pnipiirasrens (1). 

 This culture also produces rhodomycius A and B. 



Remarks: See rhodomycins. 



Method of extraction: See rhodomycin A. Crude 

 isorhodomycin A from paper chromatography 

 taken up in a small amount of ethanol. A drop of 

 concentrated HCl added. Cooling gives crystals 

 (2). 



Chemical and physical properties: Isorhodomycin 

 A: Dark red prisms; m.p. 220°C. Soluble in water 

 and low-molecular weight alcohols. Very slightly 

 soluble in benzene and chloroform. Insoluble in 

 ether and i)etroleum ether. Red fluorescence under 

 ultraviolet light. Ultraviolet light -absorption 

 spectrum maxima at about 235, 305, 525, 551, 563, 

 and 610 niyu (methanol). [q|606-7ro = +268° dz 30° 

 (c = 0.1 per cent in methanol). Cjo-iiHog-siOsN ■- 

 HCl: C = 54.25%; H = 6.84%; O = 27.92%; N = 

 3.12%; CI = 7.3%. Perchlorate: Thin red needles; 

 m.p. 177°C (2). Isorhodomycin B: Crimson-red 

 substance (3). 



Biological activity: Active on Staph, aureus (2). 



References : 



1. Lindenbein, W. Arch. Mikrobiol. 17: 361- 



383, 1952. 



2. Brockmann, H. and Patt, P. Chem. Ber. 



8a: 1455-1468, 1955. 



Kanamycin A 



Produced by: Streptomyces kanamyceticus. 

 Broths contain a second, butanol -soluble sub- 

 stance, active on B. subtilis (2), as well as kana- 

 mycin B (see next abstract). Rf values for the B. 

 subtilis factor, kanamycin A and B, respectively, 

 are 0, 0.1 to 0.26, and 0.21 to 0.37 on paper chro- 

 matography (2 per cent p-toluene sulfonic acid) 

 (9). 



Method of extraction: I. Adsorbed from l)roth- 

 filtrates on IRC-50 (Na+ form), and eluted with 

 HCl. Eluate neutralized, diluted, and resorbed 

 on IRC-50 (regenerated with NH4OH). Eluted 

 with 0.2 X NH4OH; eluate concentrated in vacuo, 

 diluted with methanol, and adjusted to pH 8.0 

 to 8.2 to precipitate kanamycin sulfate. Repeated 

 recrystallization from methanol-water at pH 7.8 

 to 8.2. Converted to the base by treatment of an 

 aqueous solution of the sulfate with a strongly 

 basic ion exchange resin, concentration, and 

 crystallization with methanol-ethanol (6). II. 

 Broths treated with IRC-50 and eluted as in I. 

 Eluates adjusted to pH 6.0 to 8.0, evaporated 

 in vacuo, and lyophilized. Powder taken up in 

 methanol, filtered, and acetone added to give a 



l)recipitate. Precipitated as the reineckate, then 

 converted to other salts (2, 3). 



Chemical and physical properties: Tetraacidic 

 l)ase. Base: Soluble in water. Insoluble in non- 

 polar organic solvents (10). [afo = +146° (c = 1 

 percent in 0.1 X H)S04). Po.sitive ninhydrin, Mo- 

 lisch, and Elson-Morgan tests (6). The two latter 

 tests were at first mistakenly reported as being 

 negative (2). Blue-violet color with the biuret 

 test (24). Negative reducing sugar, Tollen, Saka- 

 guchi, and maltol tests (6). Stable; can be auto- 

 claved for 1 hour at 120°C in aqueous solution 

 with only 10 per cent loss of activity (10). Acid 

 hydrolysis products include 2-desoxystrept amine 

 (1 ,3-diamino-4,5,6-trihydroxycyclohexane, which 

 is also obtained from neamine) and two amino 

 sugars: 6-amino-6-desoxy-D-glucose and 3-amino- 

 3-desoxy-D-glucose (also known as kanosamine). 

 C = 44"8%; H = 7.5%; N = 11.3%. C.sHseN^Ou . 

 Structural formula (6, 7, 17) of kanamycin A given 

 in Chapter 6. Sulfate: White, irregular, prismatic 

 crystals (hydrate) (6) or plates (3). No melting 

 point; decomposes over a wide range above 250°C 

 (6). Soluble in water but insoluble in organic 

 solvents (2). [atf = +121° (c = 1 per cent in 

 H2O) (3). Hydrochloride: Hygroscopic, white, 

 amorphous powder. Very soluble in water, soluble 

 in methanol, and slightly soluble in ethanol. In- 

 soluble in acetone, ethyl acetate, butyl acetate, 

 ether, benzene, and petroleum ether. No charac- 

 teristic absorption maxima in ultraviolet light 

 (2). Infrared spectrum given in reference 2. [a],^ = 

 + 103° (c = 1 per cent in H2O). More stable at pH 

 6 to 8 than pH 2.0 (2). Reineckate: Darkens at 

 191-193°C, decomposes at 211-213°C (24). Picrate: 

 Crystalline; m.p. 225-230°C (decomposition) (6). 

 Tetra-X -acetyl kanamycin: Crystalline; m.p. 250- 

 255°C (decomposition) (6). Characteristics of a 

 variety of Schiff bases formed by kanamycin 

 given in reference 6. 



Biological activity: Active on gram-positive and 

 gram-negative bacteria, including actinomycetes 

 and mycobacteria. Relatively inactive on strepto- 

 cocci, diplococci, Clostridia, and Pseudomonas. 

 Not active on fungi (2, 18). Most active at alka- 

 line pH (18). Active /"« vivo (mice and guinea pigs) 

 on M. tuberculosis H37Rv, but is less effective 

 than isoniazid and slightly less so than strepto- 

 mycin. No cross-resistance with p-aminosalicylic 

 acid, cycloserine, streptovaricin, streptomycin, 

 or isoniazid. Partial cross-resistance with phleo- 

 mycin when E. coli is used as the test organism, 

 but not when Mycobacterium 607 is used. Cross- 

 resistance with streptothricin, neomycin, and 

 viomycin in vitro. Kanamycin causes fragilitj' of 



