Automated fluorous-assisted solution-phase synthesis of β-1,2-, 1,3-, and 1,6-mannan oligomers

• Automated flourous-assisted solution-phase synthesis of β-1,2-, 1,3-, and 1,6-mannopyranoside linkages with mannuronate donors.
• Use of the β-directing C-5 ester of mannuronate donors as a protecting group that can support the automated synthesis of short β-1,6-mannan oligomers.
• Demonstrating removal of soluble F-tagged intermediates for analysis and/or purification and subsequent return to the automated synthesis platform for further reactions.
• Fewer equivalents of glycosyl donors were needed for each glycosylation cycle than related solid-phase-based protocols.

Automated solution-phase syntheses of β-1,2-, 1,3-, and 1,6-mannan oligomers have been accomplished by applying a β-directing C-5 carboxylate strategy. Fluorous-tag-assisted purification after each reaction cycle allowed the synthesis of short β-mannan oligomers with limited loading of glycosyl donor—as low as 3.0 equivalents for each glycosylation cycle. This study showed the capability of the automated solution-phase synthesis protocol for synthesizing various challenging glycosides, including use of a C-5 ester as a protecting group that could be converted under reductive conditions to a hydroxymethyl group for chain extension.

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