Current Organic Chemistry - Volume 5, Issue 12, 2001

This work reviews the synthesis of a class of stable sugar mimics termed, C-saccharides. These compounds are stable analogs of the corresponding O-saccharides in which the interglycosidic oxygen has been replaced by a carbon atom. For the most part, this review focuses on the synthesis of C-disaccharides. The organization is based on the type of chemistry used to assemble the target and has the following sub-sections: sigmatropic approaches, synthesis based on the cationic reactivity of the anomeric carbon atom, metal-mediated processes, cyclization methodology, processes based on anionic chemistry and methods based on free radical chemistry.

The field of glycobiology has recently enjoyed an enormous expansion boosted by new discoveries of the critical functions that carbohydrates play in nature. Further research in this area and the entry of carbohydrates into the medical and pharmaceutical fields will undoubtedly require easy access to these molecules. Recombinant glycosidases and glycosyltransferases, as well as their mutants and fusion proteins have already been applied in gram or even larger scale carbohydrate synthesis. Most efficient synthetic systems require expensive sugar nucleotides to be regenerated in situ. Solid support-immobilized biosynthetic enzymes and genetically engineered microorganisms have been demonstrated as viable and highly effective avenues to make carbohydrates. The efficiency of such systems makes them ideal for industry and should, at long last, make production of complex carbohydrates economically feasible.

As other monosaccharide mimics such as the azasugars and the carbasugars (with nitrogen and carbon atom, respectively, instead of oxygen atom in the ring) the thiosugars (with sulfur atom instead of oxygen atom in the ring) have gained importance in glycobiology and as potential drugs. Biological properties of monothiosaccharides are presented and the methods for their synthesis are reviewed and analyzed. Since the report of the synthesis of 5-thio-α-D-xylopyranose, the first example of thiosugars ever described, forty years of imaginative chemistry have produced a large number of monothiosaccharides and of analogs of biological interest. The preparative chemists have at their disposal a panoply of methodologies relying on pure chemical or on biochemical means, using carbohydrate or non-carbohydrate precursors. Because the sulfur moieties can participate more readily than the corresponding oxygen moieties in heterolytical processes, the chemistry of the thiosugars and their analogs is more subtile and sometimes more delicate than that of the corresponding aldoses and alditols.