L-Hexoses are key components of many biologically relevant natural
products and pharmaceuticals. As rare sugars, L-hexoses are not readily
obtained from natural sources. Access to L-hexose building blocks from
commercially available and inexpensive D-sugars is highly desirable from
the viewpoints of organic synthesis and drug discovery. As demonstrated
by the convenient preparation of L-glucosyl, L-galactosyl, and
L-mannosyl fluorides from readily available β-D-C-glucosyl,
β-D-C-mannosyl, and β-D-C-galactosyl derivatives, we
describe a novel and efficient approach to the demanding L-glycosyl
fluorides. The transformation features the installation of anomeric
hydroxymethyl group under mild conditions and head-to-tail inversion of
sugar rings through radical decarboxylative fluorination of uronic
acids. The power of this protocol is highlighted by the first assembly
of a pentasaccharide repeating unit of Pseudomonas ATCC 31554
extracellular polysaccharide (S-88). This synthesis relies on the
efficient extension of sugar chain at the sterically hindered hydroxy
group and the facile introduction of L-mannosyl unit using L-mannosyl
fluoride as glycosylating agent. The methods developed in this work
would provide new tools to the arsenal of synthesis of L-sugar building
blocks and of assembly of glycans containing L-sugar
moieties. |