Deep understanding of the structure-property relationships of polysaccharide derivatives depends on the ability to control the position of the substituents around the monosaccharide ring and along the chain. Equally important is the ability to analyze position of substitution. Historically, both synthetic control and analysis of regiochemistry have been very difficult for cellulose derivatives, as for most other polysaccharide derivatives. With the advent of cellulose solvents that are suitable for chemical transformations, it has become possible to carry out cellulose derivatization under conditions sufficiently mild to permit increasingly complete regiochemical control, particularly with regard to the position of the substituents around the anhydroglucose ring. In addition, new techniques for forming cellulose and its derivatives from monomers, either by enzyme-catalyzed processes or chemical polymerization, permit us to address new frontiers in regiochemical control. We review these exciting developments in regiocontrolled synthesis of cellulose derivatives and their implications for in-depth structure-property studies.

Aminated polysaccharides have been extensively investigated for a wide range of biomedical applications. To achieve targeted properties such as solubility and miscibility, it can be beneficial to modify the polysaccharide hydroxyl groups selectively while leaving the amino groups unmodified. This tends to be difficult because of the higher reactivity of primary amines than hydroxyl groups toward electrophilic reagents. We describe herein a new method that can produce O-acylated, aminated polysaccharides with extremely high selectivity. In this procedure, 6-azido-6-deoxy-cellulose esters are synthesized from 6-bromo-6-deoxy-cellulose esters. The azide groups are then selectively and mildly reduced using the Staudinger reaction to produce 6-amino-6-deoxy-2,3-di-O-acyl-cellulose derivatives. This demonstrates the effectiveness of the Staudinger reduction on a polysaccharide substrate in the presence of easily reducible ester groups.

The control of regiochemistry in the synthesis of polysaccharide derivatives is one of the most significant scientific challenges in the field. Its importance is only further highlighted by the individual successes in synthesis of regioselectively substituted derivatives, in particular cellulose esters and ethers, over the last 20 years. The availability of these samples and studies of their properties versus randomly substituted analogs has shown clearly that properties like solubility, aggregation phenomena, and optical properties depend heavily on the regiochemistry of substitution. We report here on the onepot synthesis of novel 6-bromo-6-deoxy-2,3-O-acylcellulose derivatives, which as more organic soluble derivatives of 6-bromo-6-deoxycellulose should allow broader exploitation of the highly regioselective cellulose 6-bromination chemistry. We illustrate the potential of these new derivatives by conversion to 6-cyano-6-deoxycellulose esters.Keywords Cellulose ester Á Regioselective synthesis Á 6-Bromo-6-deoxycellulose Á 6-Cyano-6-deoxycellulose Á Polysaccharide derivative