Streptamine synthesis

Perhaps the greatest utility of (36-39) (and many of their precursors, such as 41, 42 and 48) is as starting points for the synthesis of highly functionalized cyclohexanes. For example, (38) has been converted in five steps (overall yield 70-75%) to streptamine (57) the key step is selective ring-opening with hydrazine to give intermediate (56) (75AG(E)630). 

Crystallography, of melezitose, II, 14 Cuto-cellulose, III, 187 Cyanohydrins, in synthesis of higher-C sugars, I, 1-36, 37, 38 Cyclization, of hexose derivatives, III, 53 Cycloamyloses, III, 254 305 V, 266 Cyclohexane, 1,3-diamino-2,4,5,6-tetra-hydroxy-. See Streptamine. 

The enantiomeric purity of the bicyclic 3,6-dihydro-277-l,2-oxazine 3 was determined by H NMR of the D-camphor-10-sulfonyl derivative and was found to be >95%. The configuration of this compound was assigned by comparison with the reported optical rotation data, as (1 S,4R). This synthetic approach was utilized in the enantioselective synthesis of conduramine and streptamine analogs91. 

Aminocyclitols are oxidized if they have axial hydroxyl groups, and here, again, the axial hydroxyl groups are attacked. The sensitive amino group must be protected during the oxidation—conveniently, by means of a ben-zyloxycarbonyl group. He3ms and Paulsen i catalytically oxidized iV-ben-zyloxycarbonyl-DL-myo-inosamine-4 (74r-75) to iV-benzyloxycarbonyl-DL-2-keto-mj/o-inosamine-4 (76-77) in the presence of Adams catalyst this constituted the first synthesis of a cyclic amino ketone. This reaction is an important step in the streptamine syntheas devised by these authors. 

At one time, there was much interest in using dibromotetrols for the synthesis of streptamine (107, R = H), and thence, streptomycin (151, G = guanidino). Reaction of certain dibromo tetraacetates (74 and 105) with ammonia in hot dioxane gives small yields of diaminotetrols, the configurations of which have not been fully established, but the products differ from natural streptamine. ... 

Ito and co-workers have reported the synthesis of ribostamycin from 3, 4 -dibenzyl-tetra-N-(benzyloxycarbonyl)-neamine and 2,3,5-tri-O-benzyl-D-ribofurano-sylchloride (Sect. III.2.). An alternative synthesis of ribostamydn and biologically inactive isomers starts with 4-acetyl-N,N -dicarbo-benzoxy-2-deo3 streptamine, which reacts with 2,3,4-tri-O-benzoyl-D-ribofurano l chloride in the presence of AgC104-Ag2C03 to the tricyclic 5-0-j3-D-ribofurano l-2-deoxystreptamine Butirosin has been synthesised by S. Umezawa and co-workeis from protected ribostamycin (Sect. III.2.3). 

Another synthesis of 95 (and 97) reported by Umezawa and co-workers involved the condensation of 6-azido-2,3,4-tri-0-benzyl-6-deoxy-a-D-glucopyranosyl chloride (98) with the protected 2-deoxy-streptamine 99. The 4- (100) and 6-glycoside (101) were obtained, and from these were prepared 95 and 97, respectively. 

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. ... 

A mutant strain of Micromonospora purpurea synthesized gentamicin antibiotics on being fed with the inososes (505) and (506), which are presumably converted into streptamine and 2-deoxystreptamine, respectively, prior to incorporation into the intact antibiotics. A mutant strain of S.fradiae synthesized the pseudotrisaccharide ribostamycin (see Vol. 10, p. 131) instead of the pseudotetrasaccharide neomycin. After a second and reverse mutation, new colonies again synthesized neomycin, indicating that ribostamycin may be an intermediate along the biosynthetic pathway leading to neomycin. A chemical synthesis of neomycin C (507) from a derivative of ribostamycin is shown in Scheme 85. ... 

Yoshikawa M, Kamigauchi T, Ikeda Y, Kitagawa I (1981) Chemical transformation of uronic acids leading to aminocyclitols. IV. Synthesis of hexaacetyl-streptamine from N-Acetyi-D-glucosamine by means of electrolytic decarboxylation. Chem Pharm Bull 29 2582-2586... 

Recently the techniques of mutation and genetic manipulation have introduced new approaches to restructuring these pathways so that new metabolites are synthesized. In its simplest form a mutation can be introduced to prevent the synthesis of an intermediate substrate (such as M in Figure 6.19), and a replacement for it can be fed to the fermentation. With luck this replacement may be introduced into the metabolites. The effect is similar to the supplying of precursors for the side chain of the penicillins. This technique was used in 1969 to replace the amino sugar 6-deoxystreptamine in neomycin B with its analogue streptamine in hybrimycin A1 (Figure 6.12). 

Viomycin has been shown to inhibit protein synthesis but not to cause codon misreading in the bacterial ribosomal system. Thus, the base properties of antibiotics alone seem not to be enough to cause miscoding, which confirms the notion that streptamine or deoxystreptamine moieties of aminoglycoside antibiotics are essential for miscoding 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... 

---