Regioselective synthesis of 6-amino- and 6-amido-6-deoxypullulans

• Published in: Cellulose (London) Vol. 21; no. 4; pp. 2379 - 2396
• Main Authors: Pereira, Junia M, Edgar, Kevin J
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer-Verlag 2014; Springer Netherlands; Springer Nature B.V
• Subjects: azides; Azides (organic); bioactive properties; Biocompatibility; Biological activity; Biomedical materials; Bioorganic Chemistry; Bromination; Ceramics; Chemical synthesis; Chemistry; Chemistry and Materials Science; Composites; Derivatives; Drug delivery systems; drugs; Esters; Glass; Natural Materials; Organic Chemistry; Original Paper; Physical Chemistry; Polymer Sciences; Polysaccharides; Pullulan; Regioselectivity; solvents; Sustainable Development; Toxicity; Staudinger reaction; Synthesis; Bromination; Cationic; Amino; Drug delivery; Polysaccharide; Esterification; Amido
• ISSN: 0969-0239; 1572-882X
• DOI: 10.1007/s10570-014-0259-6

Hydrophobically modified polysaccharides that contain amine and amide groups possess valuable features for drug delivery and other applications. These chemical groups are known to play a fundamental role in the biological activity of important polysaccharides. Pullulan is known for its non-toxicity and biocompatibility, therefore, we have applied the versatile Staudinger reaction for the synthesis of regioselectively substituted pullulan derivatives containing amine or amide groups with promise for biomedical applications. The synthesis began with the regioselective bromination of pullulan at C-6 with N-bromosuccinimide and triphenylphosphine, providing 6-bromo-6-deoxy-pullulan, which is soluble in a range of organic solvents and therefore is a dynamic intermediate for the synthesis of other pullulan derivatives. Azide displacement of bromide from 6-bromo-6-deoxy-pullulan esters yielded the corresponding 6-azido-6-deoxy-pullulan esters. Staudinger reduction of these azides efficiently and chemoselectively afforded the corresponding amino- or amidopullulans.