Synthesis of protected glucose derivatives from levoglucosan by development of common carbohydrate protecting group reactions under continuous flow conditions

Abstract

Common carbohydrate protecting group reactions under continuous flow processes are reported in the context of producing partially-protected glucose building blocks from levoglucosan. Benzyl ether protection was demonstrated without the use of NaH using barium oxide, which, however, pointed to the need for forms of this catalyst not as susceptible to close packing under flow. Acylation conditions were developed under continuous flow in acetonitrile and avoiding pyridine. Ring-opening the derivatized levoglucosan with propanethiol was also demonstrated producing S-alkyl 2,4-di-O-benzyl-glucopyranoside building block in 2 rather than 12 steps in increased overall yield.

Hydrodeoxygenation of potential platform chemicals derived from biomass to fuels and chemicals

“…Limited examples of the regioselective derivatization of OH groups in levoglucosan include enzymatic acylation 53 and continuous-flow benzylation over a BaO catalyst. 54 However, the products of these systems are not useful as substrates for reductive conversions. Deoxydehydration (DODH) and double-hydrodeoxygenation reactions, which have been recently attracting much attention in the reductive conversion of sugar-derived compounds and are explained later, cannot be applied to levoglucosan because both pairs of vicinal OH groups ( i.e.…”

Nucleophilic Ring‐Opening of 1,6‐Anhydrosugars: Recent Advances and Applications in Organic Synthesis

“…[59] Ring-opening of anhydrosugars by alkyl thiols have been performed using BF 3 • Et 2 O [60] or TMSOTf under continuous flow conditions. [61] Functionalized thioarylglycosides have been obtained by various transformations of the primary hydroxy group released in the ring-opening step. [62][63][64] Karban et al reported for example the preparation of deoxyfluorinated thioglycoside donors for the synthesis of original disaccharides and T n antigen analogues.…”

“…Other conditions have been also studied including PhSTMS/TMSOTf [56] and PhSH/TsOH [59] . Ring‐opening of anhydrosugars by alkyl thiols have been performed using BF 3 ⋅ Et 2 O [60] or TMSOTf under continuous flow conditions [61] …”

Production and purification of crystallized levoglucosan from pyrolysis of lignocellulosic biomass

“…3 Levoglucosan is conventionally synthesized from D-glucose by attaching the 6-OH group to the anomeric center to form a second ring structure. 4 The commonly used synthesis route consists of a series of tedious, time consuming and expensive steps involving the protection of (reactive) hydroxyl groups, activation of the anomeric center in the saccharide, and subsequent removal of the protecting groups. 5 Without the use of protecting hydroxyl groups, it is nearly impossible to convert glucose into a 1,6 anhydrosugar derivative without damaging the inner glycosidic bond.…”