2- deoxy-2-aminoglycosides

These methods complement other approaches [159] to the preparation of 2-deoxy-2-aminoglycosides and serve to further emphasize the rich diversity of products available from the glycals. 

Aminoglycoside Biosynthesis. The biosynthesis of the aminoglycosides has been extensively studied and reviewed (117—119). Perhaps the most interesting aspect is the biosynthesis of 2-deoxystreptamiae (1, R = H), in which the C-1 and C-6 of a D-glucose molecule become the C-1 and C-2 of 2-deoxystreptamiae by way of the intermediate 2-deoxy-j //(9-iaosose. The details of this conversion are stiU unclear. 

Fig. 7 Schematic representation of the conformational differences (highlighted with a dotted box) exhibited by aminoglycosides in the binding pockets of RNA (a) and some of the enzymes involved in bacterial resistance (b). The glucose, 2-deoxy-streptamine and ribose units are numbered as I, II and III respectively...

Fig. 9 Schematic representation of the target conformationally locked aminoglycosides (2-4) and the deoxy derivatives (5, 6). The numbering employed for the different sugar units is indicated for neomycin-B (compound 1)...

Following on the discovery of streptomycin and its streptamine-based relatives (Figure 1.2), a new generation of the aminoglycosides derived from 2-deoxy-streptamine (DOS) was not long in coming (Figure 1.3). For a variety of reasons, many of these compounds have not been employed as hnman therapeutics for... 

The facile formation of the iodo compound, and the subsequent reduction with tributyltin hydride opens a new access to 2-amino-2,3-dideoxy-D-glucose (D-lividosamine) present in various aminoglycoside antibiotics [92], The same strategy been used in the synthesis of C-lO -C-l fragment of boromycin [93]. Displacement of the C-3 imidazylate ester of a 2-azido-2-deoxy-a-D-altropyranose derivative with benzoate occurred readily [94], compared with the corresponding tosylate [95],... 

D. H. R. Barton and R. Subramanian, Reactions of relevance to the chemistry of aminoglycoside antibiotics. Part 7. Conversion of thiocarbonates into deoxy-sugars, J. Chem. Soc. Perkin Tram. 7 1718 (1977). 

Antibiotic 34-1 (207) is the most recent of several known antibiotics (34-2 X-14881 E=8-0-methyl-3, 34-3 6-deoxy-8-0-methylrabelomycin 155, 34-4 8-0-methylrabelomycin 156). All are active against gram-positive bacteria and were isolated from Streptomyces fradiae strain 34, which is a construct obtained by intraspecific protoplast fusion of two S. fradiae strains. The parent strains were known as producers of the aminoglycoside antibiotic neomycin and the macrolide antibiotic tylosin, respectively [146]. Because of its reduced C-1 carbonyl, 207 resembles emycin A and hatomarubigin C (203), its closest relative. 

Inosamydns (compounds 93-06 see pg. 321) are monoaminocyclitol-contain-ing aminoglycosides produced by S. hygroscopicus they are structurally related to the neomycin, paromomycin, and ribostamycin families but contain a 2-deoxy-scyllo-inosamine instead of 2-deoxystreptamine 1 as the aglycon imit [89]. 

A few other fluorinated kanamycins, including 5-deoxy-5-epi-fluoroamikacin, 5-deoxy-5-ep(-fluoroarbekacin, and their related analogs, have been prepared to study the fluorination-toxicity relationship. In contrast to the low toxicities of the 5-fluoro derivatives [121], these epi-fluoro compounds showed acute toxicity values identical to those of arbekacin and amikacin [122]. This indicates the importance of stereo-electronic effects of the fluoro group at position 5 of the 2-deoxystreptomine moiety in toxicity of aminoglycoside antibiotics. 

Trehalosamine (433), an a,a-(l l)-linked disaccharide produced by Streptomyces lavendulae, is an aminoglycoside antibiotic composed of D-glucose and 2-amino-2-deoxy-D-glucose [252],... 

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