2‐Azido‐2‐deoxycellulose: Synthesis and 1,3‐Dipolar Cycloaddition

Abstract

Chitosan (1) was prepared by basic hydrolysis of chitin of an average molecular weight of 70000 Da, 1 H-NMR spectra indicating almost complete deacetylation. N-Phthaloylation of 1 yielded the known Nphthaloylchitosan (2), which was tritylated to provide 3a and methoxytritylated to 3b. Dephthaloylation of 3a with NH 2 NH 2 · H 2 O gave the 6-O-tritylated chitosan 4a. Similarly, 3b gave the 6-O-methoxytritylated 4b. CuSO 4 -Catalyzed diazo transfer to 4a yielded 95% of the azide 5a, and uncatalyzed diazo transfer to 4b gave 82% of azide 5b. Further treatment of 5a with CuSO 4 produced 2-azido-2-deoxycellulose (7). Demethoxytritylation of 5b in HCOOH gave 2-azido-2-deoxy-3,6-di-O-formylcellulose (6), which was deformylated to 7. The 1,3-dipolar cycloaddition of 7 to a range of phenyl-, (phenyl)alkyl-, and alkylmonosubstituted alkynes in DMSO in the presence of CuI gave the 1,2,3-triazoles 8 -15 in high yields. 2-Azido-2-deoxycellulose should be available from chitosan by diazo transfer. 1,3-Cycloadditions of 2-azido-2-deoxycellulose to alkynes should introduce 1,2,3-triazolyl side chains into chitosan and formally into cellulose, similarly as it is known for 6-azido-6-deoxypolysaccharides [20] [21] 1 ). In the following, we describe the synthesis of 2-azido-2-deoxycellulose and its reactivity in the 1,3-dipolar cycloaddition to alkynes, leading to new chitin/cellulose derivatives.

Polysaccharides: The “Click” Chemistry Impact

“…An original pathway was established by Vasella and co-workers to synthesize 2-azido-2-deoxycellulose from chitosan ( Figure 4) [34]. The azido-functionalization was carried out using a diazo transfer from trifluoromethanesulfonyl azide (TfN 3 ), among four to five reaction steps.…”

“Click” reactions in polysaccharide modification

“…This derivative has the potential to become a platform in regioselective modification, especially as an alternative to its 6-azido-6-deoxy counterpart for structureproperty relationship studies. One method developed by Zhang and coworkers [35] afforded 2-azido-2-deoxychitosan with high degree of conversion to azide (95%) using trifluoromethanesulfonyl azide (TFMSA). However, multiple steps, harsh reaction conditions, and long reaction times may impact the structural fidelity of the polymer (e.g.…”

Selective Modification of Chitin and Chitosan: En Route to Tailored Oligosaccharides

“…Zhang et al. described the synthesis of the 2‐azide derivative from 6‐ O ‐trityl chitosan, owing to the poor solubility of chitosan in organic solvents (Figure A) . The desired azide moiety was introduced by CuSO 4 ‐catalyzed diazo transfer in high yield, although the Cu salts could not be completely removed.…”