Streptamine, deoxy derivs

In a similar investigation on the deoxy derivative (33) of iSr,Ar -dibenzoyl-streptamine, Folkers and coworkers isolated a crystalline dialdehyde compound which is, accordingly, 2,4-dibenzamido-2,4,5-trideoxy-a t/io-hexodialdose (34). The compound showed no aldehyde carbonyl absorption in its infrared spectrum and was, therefore, assigned a cyclic structure. It gave a crystalline bis(diethyl dithioacetal). 

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 linkage of the hexosamines to 2-deoxystreptamine was indicated to be at positions 4 and 6 by the periodate oxidation of kanamycin, in which only the 2-deoxystreptamine survived. Conclusive evidence was afforded by the isolation of di-A -acetyl-2-deoxy-5-0-methyl-streptamine from the hydrolysis products of methylated tetra-Af-acetylkanamycin. In addition, the isolation, from this hydrolyzate, of 3-acetamido-3-deoxy-2,4,6-tri-0-methyl-a-D-glucose demonstrated that kanosamine is present as the pyranoid form in kanamycin. Earlier evidence that both hexosamines are present in kanamycin as pyranoid forms had been obtained from periodate-oxidation studies on tetra-iV-acetylkanamycin. At pH 2.5, this derivative rapidly consumes 2 moles of periodate per mole, with the formation of 1 mole of formic acid and no formaldehyde. Examination by paper chromatography of the products of hydrolysis of the reaction mixture by strong acid showed the presence of 2-deoxystreptamine and kanosamine but not of 6-amino-6-deoxy-D-glucose. 

A synthesis of hexa-acetyl streptamine (14) from 2-acetamido-2-deoxy-D-glucose is outlined in Scheme 5. The tritium-labelled 2,6-dideoxystreptamine (15) has been prepared from a trihydroxycyclohexanone derivative by a sequence of standard reactions that included the reduction of the ketone group with sodium borotritide. ... 

Variously derivatized 2-deoxy- and 2,5-dideoxy-streptamines have been synthesized 2,5-dideoxystreptamine was prepared from kanamycin by a simple procedure, and 5 0-(2,3-dideoxy-a-D-e 7r/iro-hexopyranosyl)-2-deoxy-strepta-mine dihydrochloride was obtained by glycosidation of a 2-deoxystreptamine derivative with tri-O-acetyl-D-glucal and hydrogenation. " The preparation of a 5-aminocyclohexanetetrol from kanamycin A is mentioned in Chapter 18. 

Selective periodate oxidation of neamine derivatives can lead to novel aminoglycosides, which are analogues of sorbistin antibiotics, as shown in Scheme 2 likewise cleavage of the C-3,C-4 bond of the neosamine unit led to the acetalated glycoside (10) of 2-deoxy-streptamine. ... 

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... 

There have been many syntheses reported this year in quest of compounds with improved biological activity. Syntheses which involve glycosylation of streptamine derivatives have included the preparation of 4-0-(2-amino-2-deoxy-a-D-glucopyranosyl)- and 4-0-(6-amino-6-deoxy-a-D-glucopyranosyl)-2,5-dideoxystreptamine, the latter showing remarkable antimicrobial activity, ... 

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... 

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. ... 

Purified transamidinase preparations from S. griseus and 5. hikiniensis and a crude preparation from S. hluensis catalyzed, when incubated in the presence of L-arginine, the formation of phosphate esters of N-amidino-scyZ/o-inosamine, N-amidino-streptamine and N-amidino-2-deoxy-streptamine from phosphate esters of scy/Zo-inosamine, streptamine and 2-deoxy-streptamine, respectively. None of the enzyme preparations, however, catalyzed the addition of a second amidine group to these monoguanidinated molecules. It is not known whether this second guanidine group is derived via another transamidination reaction or by a different mechanism. 

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