Kanamycine

Among the older aminoglycoside derivatives, kanamycin A and sisomicin were, at one time, a significant part of medical practice, but have now been largely replaced by the compounds Hsted in Table 1. Streptomycin is stiH used in a few restricted situations. 

N-ethyl kanamycin A (153) has some resistance to APH(3 ), ANT(2 ), and AAC(3). Butakacin [59733-86-7] C22H N 0 2 t i l-A/-(3)-2-hydroxy-4-aminobutyl derivative of kanamycin A (154), has antimicrobial properties similar to amikacin. A similar effect was seen with the l-A/-(l,3-dihydroxy-2-propyl) derivative of kanamycin B, propikacin [66887-96-5] C22H42N 022 (155). Methylation of the 6 -amine reduces susceptibility to AAC(6 ) (156). 

The 1-epi analogue of tobramycia (4) was slightly less active than the parent, but the 3-epi was almost iaactive (166). Epimerization at the 1-position had a more detrimental effect with kanamycin A (166,167). 

R" = H), were isolated from Streptomjces hofunensis (181,182). Of these, factor 5 has the best antibacterial activity, and is comparable ia poteacy to kanamycin A (5, R = H). 3 -Deoxyseldomycia factor 5 (183) was fouad to be more active than the parent compound, while the 3 -epi analogue was less active (184). 

Kamlet-Taft solvent parameters, 2, 123 Kanamycins episulfides... 

L-(-)-7-Ami no-a-hydroxybutyric Acid N-hydroxysuccinim ide 6 -Monobenzyloxy[Pg.58]

Preparation of 1-[L-l-)-y-Bemyloxycarbonylamino-a-Hydroxybutyryl]-6 -Carbobenzoxy-kanamycin A A solution of 1.6 grams (4.6 mmol) of L-(-)-7-benzyloxycarbonylamino-... 

Preparation of the Monosulfate Salt of 1-[L-(-l-y-Amino-a-HydroxybutyrylJKanamycin A One mol of 1-[L-(-)-7-amino-o-hydroxybutyryl] kanamycin A is dissolved in 1 to 3 liters of water. The solution is filtered to remove any undissolved solids. To the chilled and stirred solution is added one mol of sulfuric acid dissolved in 500 ml of water. The mixture is allowed to stir for 30 minutes, following which cold ethanol Is added to the mixture till precipitation occurs. The solids are collected by filtration and are determined to be the desired monosulfate salt. 

A portion (950 ml) of the rich eluate was adjusted to pH 6.0 by the addition of sulfuric acid. Ultrawet K (7.0 g) in 70 ml water was added slowly to the neutralized eluate to precipitate kanamycin B dodecylbenzenesulfonate which was collected by filtration after adding filter-aid (Dicalite). The cake was washed with water and extracted with 100 ml methanol. After filtering and washing with methanol, sulfuric acid was added to the filtrate until no more kanamycin B sulfate precipitated. After addition of an equal volume of acetone to provide more complete precipitation, the kanamycin B sulfate was collected by filtration, washed with methanol and dried in vacuo at 50°C. 

The yield was highest with starch or dextrin, intermediate and about the same with sucrose, glucose, maltose and lactose and poorest with glycerol. Kanamycin was produced by media containing soybean meal, peanut meal, cottonseed meal, corn steep liquor, peptone, yeast extract or meat extract, with or without sodium nitrate. Commercially available soybean meal was recognized to be one of the best nitrogen sources. The addition of corn steep liquor, peptone, yeast extract or nitrate to the soybean meal promoted the production of kanamycin. 

The brownish white kanamycin (5 g) was dissolved in 50 ml of 60% aqueous methanol, insoluble material was removed and to the filtrate 40 ml of 60% aqueous methanol containing 2,000 mg of ammonium sulfate was added, and the precipitated kanamycin sulfate was collected, washed with 50 ml of 80% aqueous methanol, and dried. Thus. 4.5 g of kanamycin sulfate was obtained as a light brownish powder. 

Streptomyces kanamycetius Bekanamycin sulfate Kanamycin sulfate Streptomyces layendulae Cycloserine... 

Soybean meal, by fermentation Bacitracin Clavulanic acid Cycloserine Erythromycin Gentamicin sulfate Kanamycin sulfate Micronomicin Novobiocin Oleandomycin Oxamniquine Oxytetracycline Paromomycin Ribostamicin Sisomicin... 

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