Kanamycin 3 -deoxy-, synthesis

T. Tsuchiya and S. Umezawa, Studies of antibiotics and related substances. XXI. The synthesis of deoxy and chlorodeoxy derivatives of kanamycin, Bull. Chem. Soc. Jpn. 38 1181 (1965). 

T. Tsuchiya and S. Umezawa, Studies of antibiotics and related substances. XXI. The synthesis of deoxy and chlorodeoxy derivatives of kanamycin. Bull. Chem. Soc. Jpn. 38 1181 (1965). T, Suami, L. Hough, M. Tsuboi, T. Machinami, and N. Watanabe, Molecular mechanisms of sweet taste. V. Sucralose and its derivatives, J. Carbohydr. Chem. 73 1079 (1994). 

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. 

Kanamycin B has also been synthesized by S. Umezawa et al. by coupling a suitably protected neamine (Table 2, 75) with 3-amino-3-deoxy-D-glucose. The synthesis of kanamycin C has been accomplished by the same researchers through the glycosylation of 4, 6 -isopropylidine-l,3,2 -tri-N-benzyloxycarbonylparomamine (Table 2, 78) with tri-O-benzylglycosylchoride, obtained from 3-acetamido-3-de-oxyglucose. 

There were two approaches to new derivatives, (a) total synthesis or (b) partial synthesis from natural antibiotics. The initial approach by Umezawa and coworkers involved the total synthesis of 3 -0-methyl-kanamycin A (Ref. 195) (175) and 3 -deoxykanamycin A (Refs. 195a and 196) (176), which involved the condensation of the protected pseudodisaccharide 179 with the 3-0-methyl- and 3-deoxy-glycosyl chlorides (177 and 178), respectively. The functionalization of the 3 -hydroxyl group caused a remarkable effect on the antibacterial activity. The 3 -deoxykanamycin was as active as the parent antibiotic, and, moreover, it was active against both Escherichia coU carrying R factor and resistant Pseudomonas, which inactivate kanamycin by the 3 -0-phosphorylation... 

Included among the modified components of aminoglycoside antibiotics reported during the past year were 3, 4, 5,6-tetradeoxy- and 5- and 6-deoxy-and 5,6-dideoxy-neamine removal of HO-6 from the 2-deoxystreptamine residue of neamine decreased the antimicrobial activity relative to that of the parent neamine, whereas removal of HO-5 enhanced the activity, especially against kanamycin-resistant strains. l,2, 3,6 -Tetra-JV-benzyloxycarbonyl-5,6-0-cyclo-hexylideneneamine has been synthesized and converted into nebramine derivatives for use in the synthesis of tobramycin and 4"-epi-tobramycin. 2, 4, 6 -Triacetyl-3,3 -0-carbonyl-3 -deoxydihydrostreptobiosamine, a precursor for the synthesis of 3"-deoxydihydrostreptomycin, has been synthesized from benzyl a-dihydrostreptobiosaminide. The synthesis involved chlorination of the key... 

When the A-tosylaziridine 11 was opened with fluoride (KHFj, DMF, 150°C) initially the 2-fluoride 12 was produced, but over time the thermodynamic product 13 formed, presumably by reversal back to 11. This reaction was also utilized in the synthesis of fluorinated kanamycin derivatives." These and other syntheses of 4 -deoxy-4 -fluorokanamycins A and B are covered in Chapter 19. The synthesis of a fluorinated analogue of the acceptor of bovine (l- 4)-P-D-galactosyl transferase is mentioned in Chapter 3, and the conformational analysis of some deoxyfluoro sugars by H-n.m.r. spectroscopy is detailed in Chapter 21. The use of e.i. and c.i. mass spectrometry to determine the location of a fluorine atom in deoxyfluoro glucosides is outlined in Chapter 22. 

Umezawa s group has reported the synthesis of 4 -deoxy-kanamycin via the coupling of an appropriately derivatized 6-amino-4,6-dideoxy-D-x j /n-hexosyI chloride with a streptamine derivative. The enzymic phosphorylation and antibacterial activity of the modified antibiotic were examined. Ribostamycin has been converted into butirosin B and its 3, 4 -dideoxy derivative, thus formally... 

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