2,5-Anhydro-d-Mannose End-Functionalized Chitin Oligomers Activated by Dioxyamines or Dihydrazides as Precursors of Diblock Oligosaccharides

Abstract

Diblock oligosaccharides based on renewable resources allow for a range of new but, so far, little explored biomaterials. Coupling of blocks through their reducing ends ensures retention of many of their intrinsic properties that otherwise are perturbed in classical lateral modifications. Chitin is an abundant, biodegradable, bioactive, and self-assembling polysaccharide. However, most coupling protocols relevant for chitin blocks have shortcomings. Here we exploit the highly reactive 2,5-anhydro-Dmannose residue at the reducing end of chitin oligomers obtained by nitrous acid depolymerization. Subsequent activation by dihydrazides or dioxyamines provides precursors for chitin-based diblock oligosaccharides. These reactions are much faster than for other carbohydrates, and only acyclic imines (hydrazones or oximes) are formed (no cyclic N-glycosides). α-Picoline borane and cyanoborohydride are effective reductants of imines, but in contrast to most other carbohydrates, they are not selective for the imines in the present case. This could be circumvented by a simple two-step procedure. Attachment of a second block to hydrazideor aminooxy-functionalized chitin oligomers turned out to be even faster than the attachment of the first block. The study provides simple protocols for the preparation of chitin-b-chitin and chitin-b-dextran diblock oligosaccharides without involving protection/ deprotection strategies.

Functionalisation of the non-reducing end of chitin by selective periodate oxidation: A new approach to form complex block polysaccharides and water-soluble chitin-based block polymers

“…Preparative and analytical gel filtration chromatography (GFC) were used for fractionation of chitin oligosaccharides and fractionation of products, respectively, as described earlier 12 . In brief, both systems were composed of Superdex 30 columns (BPG 140/950 (140 x 950 mm) and HiLoad 26/600 (26 x 600 mm), respectively) connected in series, continuously eluting ammonium acetate (AmAc) buffer (0.15 M, pH 4.5 and 0.1 M, pH 6.9, respectively).…”

“…Chitin oligomers (AnM) were prepared by nitrous acid (HONO) degradation as described earlier 12 . In brief, chitosan (FA = 0.48) was degraded using an excess of HONO (1.3 moles of HONO per mole GlcN) overnight in the dark at 4 °C.…”

“…AnM oligomers, where n corresponds to DP-1, were prepared by nitrous acid depolymerisation as described earlier 12 . The water-soluble oligomers (n = 0-8) were isolated by GFC fractionation to obtain oligomers of specific DP.…”

“…AnM oligosaccharides have previously been subjected to reducing end activation by a dioxyamine (PDHA) and a dihydrazide (ADH) to form precursors for AB-type block polysaccharides 12 . Such activated AnM oligomers were used to prepare AnM-b-dextran diblocks.…”

“…Reaction of oxidised AnM oligomers with such dioxyamines or dihydrazides may form a range of new complex structures. In the present work we first study the reaction of periodate oxidised AnM with an excess PDHA or ADH using the previously developed two-step reductive amination protocol 12 to assess the relative reactivities of aldehydes at the reducing and non-reducing end (Figure 1c). Secondly, we reacted oxidised AnM oligomers with a sub-stoichiometric amount of PDHA to obtain a discrete distribution of a new type of water-soluble chitin block polysaccharides composed of a progressively increasing number of AnM blocks reacted through both ends.…”