title: Synthesis of benzyl protected β-D-GlcA-(1→2)-α-d-Man thioglycoside building blocks for construction of Cryptococcus neoformans capsular polysaccharide structures.
abstract: In a project targeting the synthesis of large oligosaccharide structures corresponding to the Cryptococcus neoformans GXM capsular polysaccharide, an easy access to thiodisaccharide building blocks comprising a β-linked glucuronic acid moiety and a 6-O-acetyl group was required. Several pathways to such building blocks have been investigated, addressing the problem of constructing a β-linked glucuronic acid residue protected with groups that are orthogonal to a primary acetyl group. Two efficient routes have been developed, one using benzoylated glucosyl donors to form the β-linkage followed by a change of protecting groups to benzyls and subsequent introduction of the carboxyl function and the acetyl group. The second route explored the possibility to achieve β-selectivity using glucuronyl donors without acyl protecting groups. BF3-etherate promoted glycosylations with benzyl (2,3,4-tri-O-benzyl-α-D-glucupyranosyl)uronate trichloroacetimidate in the presence of nitrile solvents and at low temperatures reproducibly gave good yields of disaccharides with high β-selectivity. Furthermore, the use of recently reported glucuronyl thioglycoside donors protected with a cyclic 2,4-silylene acetal was found to represent another efficient and completely β-selective way to desired disaccharide building blocks.
authors.affiliation: Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Guazzelli
authors.affiliation: Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ulc
authors.affiliation: Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address: stefan.oscarson@ucd.ie.
authors.forename: Stefan
authors.initials: S
authors.lastname: Oscarson
mesh_terms: D002236:Carbohydrate Conformation; D060326:Chemistry Techniques, Synthetic; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000378:metabolism*; D062607:Fungal Capsules / Q000187:drug effects* / Q000378:metabolism*; D006031:Glycosylation; D011134:Polysaccharides / Q000737:chemistry* / Q000378:metabolism*; D013865:Thioglycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D011134:Polysaccharides; D013865:Thioglycosides
keywords: Oligosaccharide synthesis; Stereoselectivity; Thiosaccharide blocks; Uronic acid donors