Carbon-linked disaccharides

From prior attempts at FruA-catalyzed DHAP additions to glyoxal or glutaric dialdehyde no product had been isolated, probably because the dialdehydes can cause cross-linking of the protein and thereby irreversibly destroy its enzymatic activity. On the other hand, hydroxylated aldehydes were assumed to form stable intramolecular hemiacetals in aqueous solution, which may mask the reactivity of free dialdehydes. Using the branched-chain glutaric dialdehyde 38 as a potential precursor to carbon-linked disaccharide mimetics (Scheme 2.2.5.14), we... 

A. Dondoni, L. Kniezo, and M. Martinkova, A stereoselective hetero-Diels-Alder approach to carbon-carbon linked disaccharides, J. Chem. Soc. Chem. Commun. p. 1963 (1994). 

Anomeric radicals can be trapped by sugars having an exo-methylene group. This principle has been applied to C-2 exo-methylene lactones, opening the way to the interesting new class of carbon-linked disaccharides [113,114] (Scheme 30). 

Reductive metallation must now be performed at room temperature for the electron transfer to proceed at a reasonable rate and under Barbier conditions. At this temperature, the intermediate reagent is stable enough for a carbon-carbon bond formation in the presence of the carbonyl compound (Barbier conditions) because without the latter, it would -eliminate or protonate. This simple procedure is mild enough to be extended to the synthesis of a carbon-linked disaccharide, as shown in Figure 17, for the preparation of the derivative of the C-linked mimic 24 of the a-D-marmopyranosyl(l->2)-D-glucopyra-noside from sulfone 22 and aldehyde 23. ... 

Furthermore, the chelation-controled facially selective cyclocondensation of chiral alkoxy aldehyde 194 with diene mixture 195 in the presence of magnesium bromide in benzene gave the carbon-linked disaccharide (196) as a single product in 79% yield (Scheme 28). 

More recently, Danishefsky reported a fully synthetic route to tunicamin-yluracil (274) derived from tunicamycin (85JA7761) and hikosamine (284) (85JA7762). Cyclocondensation of the ribosederived aldehyde (260) (84JOC1955) (Scheme 35) with diene 259 under catalysis by Eu(fod)3 (83JA3716) afforded an 86% yield of the carbon-linked disaccharide 261. Ozonolysis of 261, followed by oxidative treatment and esterification, furnished the /3-hydroxy ester 262 and its benzyloxymethyl ether 263. 

Work in this area has also been carried out with noncyclic carbohydrates. Reaction of the nitro sugar 289 with cyclopentanedienone gave a mixture of 291 and 290 in a 1.9 1 ratio (Scheme 52) [78]. Dondoni used his masked formyl derivative in a hetero-Diels-Alder approach to carbon-linked disaccharides. Cycloaddition of 293 with ethyl vinyl ether gave a mixture of isomers the major compound, 294, is shown in Scheme 52. The cycloadduct was then converted to 295 via standard methods [79]. 

SYNTHETIC STRATEGIES FOR CARBON-LINKED DISACCHARIDES AND PSEUDOSACCHARIDES... 

In a further study on the carbon-linked disaccharides, the Wittig ylide (69)," a C4 synthon, derived from ethyl acetoacetate, was envisaged as a homolagative precursor for the... 

Isoxazolines (52) and (53) were obtained from coupling of the xylose nitrile oxide (54) with the alkene (55) (Scheme 3). Reductive hydrolysis of these products gave the carbon-carbon linked disaccharides (56) and (57), the latter by way of a C-2 epimerisation during the reaction. ... 

Bidirectional chain extension of dihydroxy dialdehydes gives rise to carbon-linked disaccharide mimetics (e.g., 43, 45, 46) by simple one-pot operations [115,117]. The latter may be obtained as single diastereomers in good overall yield even from racemic precursors (especially cycloolefins), if the tandem aldolization reactions are conducted under conditions of thermodynamic control (Fig. 19). Typically, the thermodynamic advantage favors the trans (43) and equatorial attachments (45, 47) of the sugar ring by far, so that the... 

In early work [165] on the synthesis of the pentasaccharide (236), the azide (237) was condensed with (238) [an intermediate in the preparation of (237)]in the presence of silver perchlorate and polyvinylpyridine to give the a-linked disaccharide (239) in 60 % yield and this on acetolysis gave the disaccharide (240) which contains the potential terminal disaccharide unit of the Forssman antigen. Compound (240) was converted into the glycosyl bromide with titanium(IV) bromide under carefully controlled conditions [182] and condensed with l,6-anhydro-2,4-di-0-benzyl-D-galacto-pyranose in the presence of silver carbonate to give the potential terminal trisaccharide (241) of the Forssman antigen. 

These compounds provide a rich variety of structural types and features. The two terpenoids possess the typical branched carbon skeletons of isoprenoids both compounds have diastereotopic methylene and methyl groups. Lactose is a /3-1,4-linked disaccharide of galactose and glucose glucose is the reducing residue, which at equilibrium in aqueous solution shows both anomers. The tetra-peptide, VGSE, contains four different amino... 

The existence of natural complex nucleoside antibiotics has prompted interest in their syntheses [173]. These compounds are composed of a C5 extended ribonucleoside. This extra chain of two or more carbons carries chiral centers. Some of these nucleosides, like tunicamycins or octosyl acids, can be regarded as C-linked disaccharides and their syntheses are not straightforward. Liposidomycin constitutes another class of complex nucleosides, which has been partially synthesized using a Wittig chain extension at C5 of the furanose derivative 243 [174]. 

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