Glycosyl ortho-(1-phenylvinyl)benzoates versatile glycosyl donors for highly efficient synthesis of both O-glycosides and nucleosides

Abstract

Both of O-glycosides and nucleosides are important biomolecules with crucial rules in numerous biological processes. Chemical synthesis is an efficient and scalable method to produce well-defined and pure carbohydrate-containing molecules for deciphering their functions and developing therapeutic agents. However, the development of glycosylation methods for efficient synthesis of both O-glycosides and nucleosides is one of the longstanding challenges in chemistry. Here, we report a highly efficient and versatile glycosylation method for efficient synthesis of both O-glycosides and nucleosides, which uses glycosyl ortho-(1-phenylvinyl)benzoates as donors. This glycosylation protocol enjoys the various features, including readily prepared and stable donors, cheap and readily available promoters, mild reaction conditions, good to excellent yields, and broad substrate scopes. In particular, the applications of the current glycosylation protocol are demonstrated by one-pot synthesis of several bioactive oligosaccharides and highly efficient synthesis of nucleosides drugs capecitabine, galocitabine and doxifluridine.

Merging Reagent Modulation and Remote Anchimeric Assistance for Glycosylation: Highly Stereoselective Synthesis of α‐Glycans up to a 30‐mer

“…DFT calculations shed light on the origin of the much higher stereoselectivities via remote anchimeric assistance with 6‐ O ‐levulinoyl (Lev) group than 6‐ O ‐acetyl (Ac) or 6‐ O ‐benzoyl (Bz) groups. In particular, we also demonstrate that orthogonal one‐pot glycosylation strategy based on glycosyl ortho ‐alkynylbenzoates (ABz) [20] and glycosyl ortho ‐(1‐phenylvinyl)benzoates (PVB) [38] can be successfully applied in the efficient synthesis of complex glycans with multiple 1,2‐ cis glycosidic bonds, which precludes such issues as aglycon transfer associated with orthogonal one‐pot glycosylation based on thioglycosides [39]…”

Route efficiency assessment and review of the synthesis of β-nucleosides via N-glycosylation of nucleobases

“…A similar strategy that eliminates competition of the leaving group with the nucleobase relies on irreversible sequestration of a vinylbenzoic ester (Scheme 6). 65 Esterification of tribenzoylated ribose with o-(1-phenylvinyl)benzoic acid accesses a stable sugar synthon. When subjected to an iodine source this synthon affords a glycosyl cation which can be intercepted by a silylated nucleobase.…”

Chemical Synthesis of the Nucleoside Antibiotic Capuramycin

“…accomplished the orthogonal one‐pot synthesis of capuramycin on the basis of the novel glycosyl ortho ‐(1‐phenylvinyl)benzoates (PVB) donors recently developed by Xiao's group (Scheme 4). [30b–c] Commencing with diacetone glucose 2 , alcohol 48 was readily prepared in 49 % overall yield over seven steps following the literatures procedures [32–33] . Levulination of 48 , cleavage of 1,2‐ isopropylidene group, benzoylation of the resulting hydroxyl groups and coupling with p ‐toluenethiol in the activation of BF 3 −Et 2 O generated thioglycoside 49 in 64 % overall yield over four steps.…”