Kanamycin B

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). 

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. 

Kanamydn A Kanamycin B Escherichia coli Klebsiella pneumoniae Pseudomonas aeruginosa... 

The next problem for H. Umezawa was to use his findings to design new kanamycin derivatives effective against resistant bacteria. The synthetic work was undertaken in cooperation with his brother. Prof Sumio Umezawa of Keio University, and one of the writers (T. Tsuchiya). The first useful derivatives active against resistant bacteria, namely, 3, 4 -dideoxy-kanamycin B (dibekacin) and 3 -deoxykanamycin A, were prepared in 1971. These were also found active against Pseudomonas known to have intrinsic resistance. These results supported the truth of H. Umezawa s theory. In the synthesis of dibekacin, the Tipson-Cohen method for introducing unsaturation, developed by one of the writers (D. Horton, 1966) for pyranoside... 

Kamlolenic acid, physical properties, 5 35t Kanamycin A, 3 25, 30 Kanamycin B, 3 35... 

Scheme 4.19. Synthesis of 3, 4 -dideoxy kanamycin B analog and pyranmycin.

Scheme 4.22. Synthesis of pyranmycin and kanamycin B analogs with AHB group at N-1.

Recently, Hanessian has reported methods for direct modification of tobramycin. Tobramycin (or nebramycin) differs from kanamycin B only in its 3 -deoxygenation, which makes tobramycin immune from the modification catalyzed by APH(3 ). A library of tobramycin analogs bearing various functionalities at 0-5 was prepared (Scheme 4.23). In general, these tobramycin analogs were less active than tobramycin (Table 4.15). However, compounds 157 and 159 showed activity against P. aeruginosa (ATCC 27853) (MIC = 12.5 fig/mL). 

Jezowska-Bojczuk et al. studied the interaction of Cu + ion with kanamycin B (5), which has an additional 2 -amino group as compared to kanamycin A (4), and in particular explored the involvement of this group in metal coordination by use of potentiometric, UV-vis, CD, and EPR methods. The presence of five amino groups in kanamycin B results in a significant lowering of the Ka value of one of its amino nitrogens (pA a = 5.74) with the Ka values for other amino... 

TABLE 8.1. Stability Constants (log p and pA Values) of Kanamycin B, Amikacin and Tobramycin Complexes with Cu +... 

Jezowska-Bojczuk et al." compared the coordination modes of tobramycin (6) with Cu + with respect to kanamycin B (tobramycin possesses a 3 -H as opposed to the 3 -OH functionality encountered in kanamycin B). The copper complexes of tobramycin formed at various solution pH values were observed to closely resemble those of kanamycin B (Table 8.1). However, the UV-vis spectrum of... 

Kanamycin is an aminoglycoside complex produced by Streptomyces ka-namyceticus. It is comprised of three components, kanamycin A being the major component and kanamycins B and C minor congeners. Kanamycin is active against many pathogenic bacteria and has been used parenterally for treatment of bovine respiratory disease, mastitis, and other infectious conditions. A popular combination used in horses and cattle with respiratory disease is kanamycin and penicillin G. It is also used orally for treatment of bacterial enteritis because limited absorption occurs after oral administration. 

Kanamycin B (4-0-[2,6-diamino-2,6-dideoxy-cx-D-glucopyranosyl]-6-0-[3-amino-3-deoxy-a-D-glucopyranosyl]-2-deoxystreptamine) [4696-79-8] M 483.5, m 170-179°(dec),... 

H. Umezawa, S. Umezawa, T. Tsuchiya, and Y. Okazaki, 3, 4 -Dideoxy kanamycin B active against kanamycin-resistant Escherichia coli and Pseudomonas aeruginosa, J. Antibiot. 24 485 (1971). 

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