title: Synthesis of a 1,3 β-glucan hexasaccharide designed to target vaccines to the dendritic cell receptor, Dectin-1.
abstract: Transformation of 3-O-benzyl-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose into 2,4,6-tri-O-benzoyl-3-O-benzyl glucopyranosyl imidate proceeded efficiently via crystalline benzyl and per-benzoylated derivatives. This imidate glycosylated di-O-isopropylidene-α-D-glucofuranose in high yield and glycosylation of the disaccharide after removal of the 3'-O-benzyl ether afforded the β1,3 linked trisaccharide in excellent yield. Di- and trisaccharides imidates were readily prepared from the furanose terminated glycosylation products but both were unreactive in glycosylation reaction with the debenzylated di- and trisaccharide alcohols. The 3'-O-benzyl perbenzoylated disaccharide pyranose derivative could be selectively debenzoylated and converted to the corresponding perbenzoylated 4,6:4',6'-di-O-benzylidene derivative. Lewis acid catalyzed glycosidation gave the selectively protected disaccharide ethylthioglycoside in good overall yield. Glycosidation of this thioglycoside donor with 5-methoxycarbonylpentanol gave the disaccharide tether glycoside and after catalytic removal of benzyl ether the resulting disaccharide alcohol was glycosylated by the thioglycoside in a 2+2 reaction to yield a tetrasaccharide. Repetition of selective deprotection of the terminal 3-O-benzyl ether followed by glycosylation by the disaccharide thioglycoside gave a protected hexasaccharide. Hydrogenolysis of this hexasaccharide followed by transesterification and second hydrogenolysis to remove a residual benzyl group gave the target hexasaccharide glycoside 1 as a Dectin-1 ligand functionalized to permit covalent attachment to glycoconjugate vaccines and thereby facilitate improved antigen processing by dendritic cells.
authors: Alberta Glycomics Centre, Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt.
authors: Hassan R H
authors: HR
authors: Elsaidi
authors: Alberta Glycomics Centre, Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada.
authors: Eugenia
authors: E
authors: Paszkiewicz
authors: Alberta Glycomics Centre, Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada. Electronic address: dave.bundle@ualberta.ca.
authors: David R
authors: DR
authors: Bundle
mesh_terms: D000818:Animals; D006031:Glycosylation; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D015394:Molecular Structure; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018074:Vaccines, Conjugate / Q000737:chemistry; D047071:beta-Glucans / Q000737:chemistry* / Q000494:pharmacology*; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D009844:Oligosaccharides; D018074:Vaccines, Conjugate; D047071:beta-Glucans; D000099181:Dectin-1; C033363:beta-1,3-glucan
keywords: Beta 1,3-glucan hexasaccharide; Beta 1,3-glucan synthesis; Dendritic cell ligand; Synthetic ligand for Dectin-1