The project showcases a promising strategy for synthesis of carrageenan oligosaccharides, which are useful tool compounds for biological studies.
Carrageenans are a type of polysaccharides found in certain seaweeds. They are widely used as gelling and viscosity-enhancing agents in the food industry. Further, carrageenans are being investigated for drug delivery applications. Oligosaccharides are useful model compounds for the highly complex carrageenan polysaccharides – but since the currently available extraction methods require extensive purification it has been suggested to instead produce them by chemical synthesis. The project showcases a promising synthetic strategy.
Carrageenans are a family of highly sulfated galactans found in the cell walls of certain red seaweeds of the Rhodophyceae class. They are able to form thermo-reversible gels or viscous solutions when added to salt solutions, and therefore serve as gelling, stabilizing and texturizing agents in the food industry. Further, carrageenan oligosaccharides are suggested for drug delivery applications, as they can be used as a matrix for preparation of extended-release tablets. Their application in polymeric microspheres for delivery of drugs in a rate-controlled manner is also explored.
Although several studies have been conducted, only a limited range of oligosaccharide structures are available and these require extensive purification. The key aim of this project therefore was to synthesize carrageenans, while a further ambition was to synthesize all ten known carrageenans from one single precursor.
A modular approach relying on the synthesis of a key β-1,4-linked digalactoside building block carrying suitable protecting groups was chosen. Each disaccharide was α-1,3-linked to each other to build up the carrageenan backbone consisting of D-galactose with alternating β-1,4 and α-1,3 glycosidic linkages.
After other methods proved unsuccessful, a set of orthogonal protecting groups was found to be surprisingly effective, affording the desired tetrasaccharide by forming the regioselective α-1,3-linkage in 55 % yield through a glycosylation between a 2,3-OH disaccharide acceptor and a trifluoroacetimidate disaccharide donor. When tested, the deprotection and sulfation steps gave the G-D6S disaccharide carrageenan successfully in 70% yield followed by debenzoylation and hydrogenation. The protection groups performed well and could be successively removed. The deprotection steps prior to the sulfation as well as the selective C-6 sulfation step were translated successfully to the tetrasaccharide. Further debenzoylation and hydrogenation will afford the G-D6S tetrasaccharide.
Once further development reaches the tetrasaccharide targets, they will serve as model compounds for structural analysis to help our understanding of the gelation process at a molecular level. This will improve fundamental knowledge about the polymer, which could pave the way for industrial applications. Further, the synthesized carrageenan oligosaccharides could help in characterization of enzymes involved in their biosynthesis and increase the understanding of algae cell wall biosynthesis.
Illustration:
Schematic model of the primary cell wall of an angiosperms cell.