Oligosaccharide Synthesis with Glycosyl Phosphate and Dithiophosphate Triesters as Glycosylating Agents

Abstract

Described is an efficient one-pot synthesis of alpha- and beta-glycosyl phosphate and dithiophosphate triesters from glycals via 1,2-anhydrosugars. Glycosyl phosphates function as versatile glycosylating agents for the synthesis of beta-glucosidic, beta-galactosidic, alpha-fucosidic, alpha-mannosidic, beta-glucuronic acid, and beta-glucosamine linkages upon activation with trimethylsilyl trifluoromethanesulfonate (TMSOTf). In addition to serving as efficient donors for O-glycosylations, glycosyl phosphates are effective in the preparation of S-glycosides and C-glycosides. Furthermore, the acid-catalyzed coupling of glycosyl phosphates with silylated acceptors is also discussed. Glycosyl dithiophosphates are synthesized and are also used as glycosyl donors. This alternate method offers compatibility with acceptors containing glycals to form beta-glycosides. To minimize protecting group manipulations, orthogonal and regioselective glycosylation strategies with glycosyl phosphates are reported. An orthogonal glycosylation method involving the activation of a glycosyl phosphate donor in the presence of a thioglycoside acceptor is described, as is an acceptor-mediated regioselective glycosylation strategy. Additionally, a unique glycosylation strategy exploiting the difference in reactivity of alpha- and beta-glycosyl phosphates is disclosed. The procedures outlined here provide the basis for the assembly of complex oligosaccharides in solution and by automated solid-phase synthesis with glycosyl phosphate building blocks exclusively or in concert with other donors.

Recent Progress in the Synthesis of Glycosyl Phosphate Derivatives

“…2, 4 → 6) (17,18). For this reason, the synthesis of glycosyl phosphate triesters has been well studied, and both the α-and β-isomers are available from various types of protected sugars (19)(20)(21)(22)(23). In addition, these triesters can be used to synthesize other glycosyl phosphate derivatives, especially sugar nucleotides.…”

“…In addition to glycosyl halides, glycosyl imidates (41), 1,2-anhydrosugars 22 ( Fig. 6) (21,42,43), and 1,2-orthoesters 24 ( Fig. 6) (23,44) have recently been used to synthesize glycosyl phosphate triesters.…”

Synthesis and Spectroscopic Characterization of Eight Chloro Cyclopentadienyl Titanium Bis (O, O-Dialkyl and Alkylene Dithiophosphate) Compounds

“…Dithiophosphate complexes of both transition and non-transition elements have received considerable interest due to their wide diversity in chemical [1]- [6] and biological systems [7] [8] O, O-Dialkyl and alkylene dithiophosphate ligands can coordinate to metal atoms in a monodentate or anisobidentate fashion [9] [10]. More recent applications of thio compounds are in the production of nanoparticles of metal sulfides [11] [12].…”

Automatisierte Polysaccharidsynthese: Herstellung eines Mannosyltriakontamers (30‐mer)

“…Dibutylphopsphat als Abgangsgruppe ermçglicht eine schnelle und effektive Glycosylierungen von 1 nach Aktivierung mit Lewis-Säure. [7] Das mit einem photolabilen o-Nitrobenzyl-Linker [8] funktionalisierte Merrifield-Harz 2 diente als Festphase für die automatisierte Synthese (Schema 1).Mit dem Mannosephosphat 1 und dem funktionalisierten Merrifield-Harz 2 wurden im automatisierten Kohlenhydratsynthesizer[5b] verschiedene a-(1,6)-Oligomannoside hergestellt (Schema 1). Für die Dreifachglycosylierungen, die mit drei ¾quivalenten des Bausteins 1 bei À15 8C durchgeführt wurden, diente TMSOTf als Aktivator.…”