Carba-Oligosaccharides

SCHEME 8.2 Carba-sugars as stable chemical probes. 

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VIII. Synthesis of Biologically Active Carba-oligosaccharides. 74... 

Carba-oligosaccharidic Alpha Amylase Inhibitors and Related Compounds. . 81... 

In the present article, the preparation of carba-sugars, amino carba-sugars, and biologically active carba-oligosaccharides will be described. 

Carba-glycosylamines [2,3,4-trihydroxy-5-(hydroxymethyl)-1 -cyclohex-ylamine] and related compounds are well known to exist as components of the antibiotic validamycin complex and carba-oligosaccharidic alpha amylase inhibitors. ... 

Treatment of 51 with an excess of sodium benzoate in DMF resulted in substitution and elimination, to yield the cyclohexene derivative (228, 36%). The yield was low, but 228 was later shown to be a useful compound for synthesis of carba-oligosaccharides. <9-Deacylation of228 and successive benzylidenation and acetylation gave the alkene 229, which was oxidized with a peroxy acid to give a single epoxide (230) in 60% yield. Treatment of 230 with sodium azide and ammonium chloride in aqueous 2-methoxyeth-anol gave the azide (231,55%) as the major product this was converted into a hydroxyvalidamine derivative in the usual manner. On the other hand, an elimination reaction of the methanesulfonate of 231 with DBU in toluene gave the protected precursor (232, 87%) of 203. 

Several mono-carba-oligosaccharidic alpha amylase inhibitors, such as acarbose and its homologs, amylostatins, trestatins, oligostatins, adipo-sins, and so on, have been isolated from cultures of micro-organisms, and considerable interest in the biochemistry and chemistry of this class of inhibitors has been stimulated. The characteristic core-structure for inhibitory action is composed of a trihydroxy(hydroxymethyl)cyclohexene moiety and a 4-amino-4,6-dideoxy-D-glucopyranose moiety, bonded by way of an imino linkage at the allylic position. A similar structural unit has been found in the antibiotic validamycins. 

Here again, it is as probes that carba-oligosaccharides find their best applications. Compounds 7 and 8 were both submitted to the action of a-(l-3/4)-fucosyltransferase in the presence of GDP-fucose. Only 7 was accepted and fucosylated to give the Lewis analog 9 showing that this enzyme has a different mode of action regarding the synthesis of Lewis s (Scheme 8.3) [16]. 

This mixture was then oxidized and homologation of the resulting ketone provided 136. After hydrogenolysis, methyl 5 a-carba-maltoside was isolated [64]. A characteristic of this method is that the rearrangement is done on the disaccharide itself. This method can thus also lead to carba-oligosaccharides through cascade rearrangements [66]. 

The preparation of amino cyclitols as building blocks for carba-oligosaccharides related to cell-surface glycans from intermediate 90 has been described." ... 

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