Finely selective protections and deprotections of multifunctional chitin and chitosan to synthesize key intermediates for regioselective chemical modifications

Site-selective protection of chitin and chitosan has been studied in detail in order to distinguish the three kinds of functional groups, which would make possible finely controlled regiospecific structural modifications. To allow reliable chemical manipulations and to establish stable protection and facile deprotection at high selectivity, benzyl was evaluated for the C-3 protection in combination with other protective groups including triphenylmethyl (trityl) for C-6 and acetyl or phthaloyl for C-2. Chitin was first tritylated and then benzylated to give 3-O-benzyl-6-O-trityl-chitin, of which each of the trityl, benzyl, and acetyl groups could be removed selectively with dichloroacetic acid, hydrogen-Pd/C, and aqueous sodium hydroxide, respectively, affording three kinds of derivatives having a reactive group at C-6, C-3, or C-2. 2-N-Phthaloyl-chitosan was also tritylated at C-6 and benzylated at C-3; the resulting fully protected product was detritylated, debenzylated, or dephthaloylated, similarly giving rise to three kinds of precursors having a reactive group only at one position. The extents of all the substitution and removal reactions proved quantitative under appropriate conditions to give structurally well-defined derivatives. They exhibited improved solubility in organic solvents, indicating high potential of these derivatives as novel convenient intermediates for designing diversified molecular architectures through regiospecific chemical modifications.