Sulfated alginates
(ASs), as well as several artificially sulfated
polysaccharides, show interesting bioactivities. The key factors for
structure–activity relationships studies are the degree of
sulfation and the distribution of the sulfate groups along the polysaccharide
backbone (sulfation pattern). The former parameter can often be controlled
through stoichiometry, while the latter requires the development of
suitable chemical or enzymatic, regioselective methods and is still
missing for ASs. In this work, a study on the regioselective installation
of several different protecting groups on ad-mannuronic
acid enriched (M-rich) alginate is reported in order to develop a
semi-synthetic access to regioselectively sulfated AS derivatives.
A detailed structural characterization of the obtained ASs revealed
that the regioselective sulfation could be achieved complementarily
at the O-2 or O-3 positions of M units through multi-step sequences
relying upon a silylating or benzoylating reagent for the regioselective
protection of M-rich alginic acid, followed by sulfation and deprotection.