Synthesis and Protecting Groups

The protecting groups used in carbohydrates are generally the same as those of mainstream organic chemistry; the difference, however, is that even a monosaccharide presents a myriad of hydroxyl groups that need protection, in either an individual (regioselective) or a unique (orthogonal) manner. Also, the introduced protecting groups may affect the reactivity of the resulting molecule or even participate in some of its reactions. Esters, together with ethers and acetals, constitute the main protecting groups for the hydroxyl groups of sugars. The popularity of esters derives from their ease of formation, generally employing readily available acid anhydrides or acid chlorides, and also the ease of removal. Although the primary role of esters introduced into carbohydrates is to protect the otherwise reactive hydroxyl groups, they can also play a role in precipitating useful chemical reactions at both anomeric and nonanomeric carbon atoms. Esters, like ethers and acetals, reduce the polarity of the carbohydrate and so improve solubility in organic solvents. Orthogonal protecting groups are those in a set that require a unique reagent for their individual removal, being unreactive to the conditions required for the removal of the other groups of the set. For example, the acetyl group (of an ester) and the benzyl group (of an ether) are an obvious orthogonal pair of protecting groups for the hydroxyl group. This concept has been much extended over recent years, to include monosaccharides that are protected in a fully orthogonal sense. Synthesis with carbohydrates would be a less complicated matter if it were confined to the natural and abundant aldoses, ketoses, and oligosaccharides. However, there often arises the need for modified monosaccharides or, perhaps, an unusual or rare oligosaccharide.