The Structure of Kanamycin B

抄録

In the course of a research for kanamycin (kanamycin A)¹⁾ purification, kanamycin B¹⁾ and kanamycin C²⁾ were isolated from the culture broth of Streptomyces kanamyceticus¹⁾. Kanamycin B was obtained in pure form by Schmitz, Fardig, O’Herron, Rousche and Hooper⁸⁾, who isolated deoxystreptamine and 3-amino-3-deoxy-D-glucose after acid hydrolysis of N-acetyl-kanamycin B. Wakazawa, Sugano, Abe, Fukatsu and Kawaji⁴⁾ reported that partial hydrolysis mixture of kanamycin B still retained some biological activity against B. subtilis, and later they⁵⁾ isolated a crystalline degradation product which had antibacterial properties.

It has been determined that in kanamycins A^6,7,8,9) and C¹⁰⁾ two aminosugars link to 4- and 6-positions of deoxystreptamine, while in neomycin-group (neomycins B C^11,12d) and paromomycin¹³⁾ the 4,5 hydroxyls of deoxystreptamine are substituted. It should be noted that neomycins are more toxic than kanamycins A and C. As compared with kanamycin A and neomycin S, kanamycin B has more than twice less toxicity than neomycins and has more than five times toxicity than kanamycin A. As reported by Wakazawa et. al.⁴⁾, kanamycin B can be determined separately from A.

In the present paper, our experiments on the structure of kanamycin B are described.

Kanamycin B base, which was prepared by the process of Wakazawa et al⁴⁾ and was recrystallized from ethanol-water, showed [α]²⁴_D+ 126° (c, 0.7 in water) and decomposed over the range of 170~190°C. It was soluble in water, but hardly soluble in organic solvent. Its molecular weight was reported to be 1,170 (Rast method, urea as solvent) by Schmitz et al.³⁾ and 385~560 (Barger method, water as solvent) by Wakazawa et al.⁴⁾ The crystals obtained in our laboratory showed molecular weight of 430~590 by the Rast method (urea as solvent, kanamycin A as standard).

N-Acetylkanamycin B^3,4) was prepared and, from its hydrolyzates, deoxystreptamine hydrochloride (molecular weight 235) was isolated in the yield of about 30% by weight. The elemental analyses of kanamycin B base and its N-acetyl derivative, together with the above data, suggested the molecular formula C₁₈H₃₇N₅O₁₀ for kanamycin B base.