Cyclic Structures for the Carbohydrates

Following his ingenious experiments, using only chemical reactions, crystallizations, optical rotation, and his brilliant deductions, Fischer was awarded the Nobel prize in chemistry in 1902 for his monumental studies on the structures of carbohydrates. 

For many, it seemed that the structures of the hexoses and pentoses had been definitively demonstrated by Emil Fischer, and that the chapter on the structures of carbohydrates was closed. However, there were certain troubling facts that were not entirely consistent with the structures proposed by Fischer. 

The carbohydrates failed to undergo certain reactions that were typical of aldehydes. Although the hexoses and pentoses were readily oxidized at C-1 under mild alkaline conditions, they did not give a positive result with the Schiff test (reaction with basic fuchsin), and they did not form bisulfite addition products, reactions that are typical of aldehydes. The cyanohydrin and phenylhydrazine reactions also went much more slowly than they did for other a-hydroxy aldehydes. 

The fact that the formation of the methyl glycosides and the pentaacetates resulted in only two isomeric forms each, suggested that D-glucose and related hexoses and pentoses existed in only two forms and not three. 

The phenomenon of mutarotation for D-glucose had been recognized since 1846. Also as early as 1856, two different crystalline forms of lactose had been obtained. 

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