Sugar Fundamentals

Sugar is a common name for any sweet, crystalline, simple carbohydrate which is an aldehyde or ketone derivative of a polyhydric alcohol (see http://en.wikipedia.org/wiki/Carbohydrate). In the mid-eighteenth century long before the structures of many common sugars had been determined, consensus was reached that sugars should be named with the ending '-ose'. The simplest carbohydrate unit is a monosaccharide, such as glucose, galactose, or fructose. In addition, carbohydrates generally adopt cyclic or ring forms adding to their unique three-dimensional complexity. As an example of the remarkable diversity even simple sugars can provide, the chemical formula of glucose (C6H12O6) actually represents ~ 120 distinct three-dimensional sugar structures. This incredible diversity rapidly increases as one considers additional functional groups, and connecting multiple sugar units together to generate sugar polymers (see http://www.chem.qmul.ac.uk/iupac/2carb/). Given the extraordinarily diverse structural and functional properties of carbohydrates - defined by differing lengths, the position of the aldehyde or ketone carbonyl, the vast array of functional groups, the specific configuration (or stereochemistry) of carbon to which each functional group is attached and the variant ring sizes – nature extensively relies upon sugars for a multitude of functions (see Sugars in Nature and Sugars in Medicine).

The same diversity that positioned carbohydrates as an essential element to all living organisms, presents a monumental challenge to the carbohydrate chemist interested in connecting sugars to target molecules (e.g. a drug, another sugar, a protein, etc.) to form glycoconjugates. The key carbohydrate coupling reaction, the glycosylation reaction, has been pursued for well over 100 years and is one of the most thoroughly studied transformations in organic chemistry. Within a typical glycosylation reaction, each monosaccharide unit has multiple reactive sites that must be selectively ‘masked’ via a plethora of protecting group strategies. In addition, the formation of the glycoside linkage can result in two different stereo configurations (like your left and right hand) that require additional steps to control. Thus, previous glycosylation strategies require an extensive array of fine-tuning that greatly limit the overall utility of carbohydrate chemistry in commercial applications.

CarboConnect (see Technology Platform) now presents a realistic opportunity for the production of a new generation of highly active and specific therapeutics.