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

Abstract

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-trimethyl-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 1H and COSY NMR and IR spectroscopy.