Synthetic strategy for selective N-modified and O-modified PEGylated chitosan derivatives

A series of PEGylated chitosan derivatives were synthesized using protection group strategy. N-mPEG chitosan derivatives were synthesized by two different synthetic routes - either by direct substitution at the amino group or using a spacer with the help of 3,6-O-diTBDMS-protected chitosan as a precursor. The use of TBDMS protection on both the hydroxyl groups of chitosan allowed modification selectively at the amino functionality. N,N,N-trimethyl chitosan (TMC) homopolymer was synthesized and utilized for the 2,2,6,6-Tetramethyl-1-piperidinyloxy (TEMPO) oxidation of the C-6-hydroxyl group. This oxidation step was optimized using various reaction conditions to obtain the 100% oxidized product N,N,N-trimethy1-O-6-carboxy chitosan. The oxidized product was then further used for selective PEGylation at the hydroxyl group of TMC by esterification. Characterization of the synthesized chitosan derivatives was carried out by H-1 and COSY NMR and IR spectroscopy. (C) 2016 Elsevier Ltd. All rights reserved.