Carba-disaccharides

In order to develop potent D-glucosidase inhibitors, a synthesis of carba-disaccharides containing valiolamine (205) was attempted by Horii and his coworkers utilizing method c. Coupling 205 with the 4-ketose 403, using NaBHjCN and hydrochloric acid, was effective in DMF, giving, after deprotection, the epimeric carba-disaccharides (404 and 405). The saturated... 

Such carba-disaccharides as validoxylamines A and B were synthesized as intermediary compounds in the total synthesis of validamycin antibiotics. Carba-disaccharides related to maltose, isomaltose, cellobiose, the trehaloses, and trehalosamine modifications have also been synthesized. 

The fact that both the stereochemistry and the substitution pattern of the sugar anomeric center is conserved allowed to realize a direct transformation of a hex-5-enopyranosides of sucrose 20 into a carba-disaccharide analogue 21 (Scheme 6), and to achieve cascade rearrangements [45]. 

SCHEME 8.3 Carba-disaccharides as stable chemical probes. 

SCHEME 8.16 Synthesis of a carba-disaccharide using a carbocationic cyclization. 

As previously stated, a distinct feature of this rearrangement is the retention of the anomeric information. This advantage is nicely illustrated by the direct synthesis of a carba-disaccharide from a disaccharide [65]. As shown in Scheme 8.35, maltose was first transformed into the thioglycoside 131. Manipulation to the free primary alcohol 132 was achieved using a classical sequence of reactions. At this point, glycosylation of methanol was realized in the presence of NCS to afford 133, and the unsaturated derivative 134 was obtained after iodination and elimination. Triisobutylaluminum induced rearrangement nicely afforded the carba-disaccharide precursor 135 in a yield of 89% as a mixture of two isomers. 

SCHEME 8.35 S3fnthesis of a carba-disaccharide using the TIBAL induced rearrangement. 

Carba disaccharide 97 has been prepared by insertion of a sugar glycosylidene carbene (made in situ from a glycosyl diazirine derivative) into OH groups of protected deoxy m o-inositoI orthoformate derivatives. ... 

Other carba disaccharides to have been prepared include carba-a-o-Glcp-, carba-a-D-Manp-, carba-P-D-Man/j- and carba-P-o-GIcNAcp- (l- 4)-l,6-anhydro-2,3-0-isopropylidene-P-D-mannopyranoses. The a-linked compounds were prepared by adding the anion of l,6-anhydro-2,3-C>-isopropylidene-p-D-mannopyranose to epoxide 98 and the P-linked derivatives were obtained from the a-linked compounds by epimerization after oxidation of the free cyclitol OH group. Further standard transformations of the free cyclitol OH also gave the cyclitol configurations noted above.In a similar way, opening of a cyclitol... 

The synthesis of the carba di- and tri-saccharides 103 has been described. and the preparation of carba-disaccharide 104 by a similar process to that reported earlier (Vol. 25, p. 214, ref. 95) has appeared. For the preparation of glycosides of cyclitol derivatives see also Chapter 3. Carbocyclic analogues of GDP fucose have been made as potential inhibitors of fucosyl transferases. ... 

By use of standard chemistry, lD-3-0-benzyl-l,2 4,5-di-0-cyclohexylidene-myo-inositol has been converted into the carba-disaccharide 78 as a potential intermediate for preparing glycosylphosphatidyl inositols. ... 

The carba-disaccharide 81 has been designed as an antigen for preparing glycoside-bond forming catalytic antibodies with catalytic groups. In its synthesis the addition of an acetylide anion to a carbocyclic ketone, followed by an OH Ns replacement, formed the key steps. 

The Perrier reaction has been utilized in the construction of various amino cyclitols. Thus, starting from A -acetylglucosamine, 1d-(1,3,5/2,4)-4-acetamido-5-amino-l,2,3-cyclohexanetriol has been prepared and glycosylated with a d-glucuronic acid derivative to produce an intermediate which, after deprotection, afforded the carba-disaccharide 86. The cyclitols 87 (R = a-D-arabinofuranosyl or 3-amino-2,3,6-trideoxy-a-L-arabinohexopyranosyl), have been prepared from... 

Carba-disaccharides 88-91 (R = a-D-arabinofuranosyl) have also been synthesized as potential antibiotics. ... 

Several examples of other glycosylated inositols are noted in Chapters 3 and 4. The syntheses of carba-disaccharides related to salbostatin and fortimycins are metioned in Chapter 19, and the syntheses of 6-membered carbocyclic nucleosides and the use of cyclitols as chiral auxilliaries in Diels-Alder reactions are covered in Chapters 20 and 24, respectively. 

In the area of carba-disaccharides, the synthesis of dicarba-a,a-trehalose, togedier widi the analogues 110a and 111 have been reported as potential trehalase inhibition. ... 

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