C-Disaccharide

The Michael dclclidon of nitro ilkdnes followed by denitration is also a useful method fot the pteparadon of C-disaccharide. The Michael addidon of glncosyl nitromethane to the levogln-cosenone ptoceeds steteoselecdvely, and subsequent denitradon gives the C-disaccharide in 68% yield fScheme 1.%) ... 

C-Disaccharide analogs of trehalose were recently [20c] prepared by using as a key step an aqueous Diels-Alder reaction between the sodium salt of glyoxylic acid and the water soluble homochiral glucopyranosil-l,3-pentadiene 19 (Equation 6.1). A mixture of four diastereoisomers in a 41 24 21 14 proportion was obtained after esterification with methanol and acetylation. The main diaster-eoisomer 20 was isolated and characterized as benzoyl-derivative. 

Figure 10.31 Synthetic route to oxygenated pyrrolizidine alkaloids, and an aza-C-disaccharide as glycosidase inhibitors.

As shown in Eq. 12.54, with glyoxylate as the dienophile, if the attack is on the si face of the diene, it would lead to the skeleton of KDO if the attack is on the re face, it would lead to the skeleton of KDN. C-Disaccharide analogs of trehalose were prepared using an... 

Martin and coworkers have used this strategy for synthesis of a- and P-(l,6)-linked C-disaccharides (Eq. 5.40).58... 

Martin has used this strategy for the preparation of (3-(l,6) and P,(3-(l,l) hnked C-disaccha-rides, as shown in Scheme 7.7.73 Such C-disaccharides are a class of nonhydrolyzable mimics of disaccharide and potential glycosidase inhibitors in the treatment of metabolic diseases (Scheme 7.7). 

PCC in the presence of 4 A MS to afford the corresponding keto sugars (175, 176), which after Tebbe methylenation led to the corresponding exoglycals, valuable intermediates for the synthesis of C-disaccharides. Dondoni el al.159 made use of PCC in the presence of powdered 4 A MS to introduce suitable formyl groups in the carbohydrate, and allowing the synthesis of >6)-linked oligosaccharides,... 

B. Vauzeilles and P. Sinay, Selective radical synthesis of /i-C-disaccharides,... 

Kishi and co-workers have proposed that O-glycosides and C-glycosyl compounds share the same conformational characteristics in solution.34 This is the case, for instance, for the C-disaccharide 27 (Fig. 15).35 It adopts a major conformation similar to that proposed for methyl 3-<9-(a-n-galactopyranosyl)-a-D-mannopyranoside (28). 

Anomeric acetates 104 have been also used as electrophiles toward alkynylindium reagents 105 under Barbier conditions. Good yields and 1,2-cA-stereoselectivities were observed during the reaction (Scheme 36). The alkynylation was applied to the synthesis of an a-(l —>6)-C -disaccharide (110) analogue of methyl isomaltoside.108... 

The first examples of C-disaccharides obtained applying radical C-glyco-sylation of sugar-derived exocyclic enones was reported by Giese and Witzel.138 The reaction of glucosyl bromide 148 and enone 154 afforded a mixture of stereoisomeric C- glucopyranosyl compounds from which pure 155 was obtained in 22% yield by precipitation (Scheme 52). 

This strategy was later refined by Stork and co-workers142 who used silicon (e.g. 164) as the tethering atom [Scheme 55a)]. The latter strategy was adapted by Sinay and co-workers143 for the synthesis of C-disaccharides (e.g. 169) by employing 8- and 9-endo radical cyclizations with the readily prepared silaketal connectors [Scheme 55b)]. 

The Henry reaction of nitro sugars and sugar aldehydes is a powerful tool for the formation of C-glycosydic bonds. A recent example is the preparation of disaccharide precursor 60 stated in Scheme 21.45 It involves a Henry reaction of nitro sugar 58 and aldehyde 59 in acetonitrile in the presence of catalytic potassium fluoride, to give nitro alcohol 60, a precursor of the corresponding C-disaccharide. 

Similar derivatives (formally being C-disaccharides with the normal and aza sugar rings) were prepared by Vogel (Fig. 37).52... 

Fig. 14 Synthesis of a C-disaccharide exploiting the Sml2 catalyzed reaction of a glycosyl pyridylsulphone.

P. Vogel, S. Gerber-Lemaire and L. Juillerat-Jeanneret, Imino -C- disaccharides and analogs synthesis and biological activity, in Imino sugars, from synthesis to therapeutic applications, ed. P. Compain and O. Martin, Wiley, 2007, pp. 87-130. 

Applying the procedure just described, Rouzaud and Sinay (65) described a stereospecific synthesis of a C-disaccharide in which a methylene group takes the place of the interunit oxygen atom. Starting from 51a and the dibromoalkene 59, the hemiacetal 60 was obtained. Reduction of 60, followed by catalytic hydrogenolysis, gave the /J-(l — 6)- C-disaccharide 61. 

Likewise, the lactol 62, obtained by addition of methyllithium to 2,3,5-tri-O-benzyl-D-arabinono-1,4-lactone, underwent a self-condensation reaction in the presence of BF3 OEt2-MeCN, to afford an anomeric mixture of two C-disaccharides 63 and 64 in 93% yield (66). 

The reaction of type i is utilized for the preparation of a variety of dicarboxylic acids. Scheme 25 shows the synthesis of a C-disaccharide (73) from a carbohydrate carboxylic acid (72) [98]. 

Scheme 25 C-disaccharides by anodic decarboxylation of carbohydrate carboxylic acids.

The replacement of the anomeric oxygen by a CF2 has been considered to obtain hydrolytically stable difluoro-C-glycosides, difluoro-C-disaccharides and difluoro-C-glycopeptides. These compounds have been synthesized [65-68], but their use as inhibitors does not seem to have been biologically validated. 

H. Berber, T. Brigaud, O. Lefebvre, R. Plantier-Royon, C. Portella, Reactions of difluoroenoxysilanes with glycosyl donors Synthesis of difluoro-C-glycosides and difluoro-C-disaccharides, Chem. Eur. J. 7 (2001) 903-909. 

T.F. Herpin, W.B. Motherwell, M.J. Tozer, The synthesis of difluoromethylene-linked C-glycosides and C-disaccharides, Tetrahedron Asymmetr. 5 (1994) 2269-2282. 

Starting from Difluorovinyl Glycosides Saccharidic derivatives that have a difluoromethylene group in the pseudo-anomeric position are important synthetic intermediates for preparation of difluoro-C-glycosides, difluoro-C-phos-phonates, and difluoro-C-disaccharides. ° ... 

The enolic double bond of a difluorovinyl group in the anomeric position is able to add a radical. It can thus afford a difluoro-C-glycoside, either directly or indirectly. When the alkylating radical is generated from a 6-halogenopyranoside, the reaction can lead to difluoro-C-disaccharide. These reactions are even more efficient if the radical has an electrophilic character (e.g., with an a-halogenoester instead of an alkyl radical). 

Figure 6.26 Synthesis of difluoro-C-glycosides and difluoro-C-disaccharides starting from difiuoroenoxysiianes/ ...

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