Kanamycin 3 -amino-3 -deoxy-, preparation

Numerous reports describe the modification of natural amino-glycoside antibiotics or products derived from them by conventional methods. 1-/ -Alkylated kanamycins can be prepared very efficiently by utilizing an O N acyl migration to protect the sugar amino-groups selectively, leaving the deoxy-streptamine amino-groups free-, a formylation-deformylation sequence then... 

The manner in which the three amino sugar moieties are combined in kanamycin (8) was deduced from the results of methylation, periodate-oxidation, and partial-hydrolysis studies. Hydrolysis of kanamycin with 6 N hydrochloric acid at 100° for only 15 minutes yields, as shown by paper chromatography and by preparative chromatography, two disaccharide components which were shown to be 2-deoxystreptamine kanosaminide and 2-deoxystreptamine 6-amino-6-deoxy-D-glucopyrano-side. Thus, both of the aminodeoxyhexoses must be linked glycosidically to the 2-deoxystreptamine, and not one to the other. It is interesting to note that the amount of each disaccharide formed during the period of hy-... 

Kanamycin A, the oldest compound of this type, has been synthesised by two Japanese research groups. S. Umezawa and co-workers linked the protected 6-0-(3-amino-3-deoxy-a-D-glucopyranosyl)-2-deoxystreptainine (Table 2, 77) with the blocked glycosylchloride, prepared from 6-amino-6-deoxyglucose. Nakajiama and co-workers have reported the synthesis of kanamycin A from the protected 4-0-(6-amino-6-deoxy-a-D-glucopyranosyl)-2-deoxystreptamine (Table 2,80) and the tri-O-benzylglycosylchloride, obtained from 3-acetaniido-3-deoxy-glucose. 

B (517) has also been synthesized from ribostamydn by introducing the 3 -deoxy and N -[(S)-4-amino-2-hydroxybutyryl] groups. Neomydn and paromomycin have been converted into their 5"-amino-5"-deoxy analogues, via the corresponding 5"-bromides, and 3 -deoxyparomamine (available by hydrolysis of lividomycin) has been transformed, by way of the action of nitromethane on its 6 -aldehyde derivative, into isomeric 6 -C-aminomethyl-3 -deoxyparomamines (519). The use of the Tipson-Cohen procedure to prepare 3, 4 -unsaturated derivatives of butirosin and kanamycin is mentioned in Chapter 12. 

Deoxy-3-fluoro-D-glucose has been used to prepare 4-amino-3-fluoro-2-hydroxybutanoic acid derivatives which were coupled to kanamycin A and B via amide links to N-1 of the streptamine unit. ... 

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