Investigation of Glycosyl Nitrates as Building Blocks for Chemical Glycosylation

Abstract

Glycosyl nitrates are important synthetic intermediates in the synthesis of 2-amino sugars, 1,2-orthoesters or, more recently, 2-OH glucose. However, glycosyl nitrates have never been glycosidated. Presented herein is our first attempt to use glycosyl nitrates as glycosyl donors for O-glycosylation. Lanthanide triflates showed good affinity to activate the nitrate leaving group.

Defining the Scope of the Acid‐Catalyzed Glycosidation of Glycosyl Bromides

“…Apart from the disaccharide, the corresponding anomeric acetate (30 %, entry 8) and benzoate (8 %, entry 9, yields based on donor 1 ) side products were also isolated from these reactions. Glycosylations in the presence of silver nitrate (AgNO 3 ), performed with and without TMSOTf, produced mannosyl nitrate, along with the trace amount of disaccharide 3 (entry 10). Glycosylation reaction in the presence of silver carbonate (Ag 2 CO 3 ) produced disaccharide 3 in 99 % yield in 10 min (entry 11).…”

Direct Glycosidation of 2‐Azido‐2‐deoxyglycosyl Nitrates

“…However, the application of these reaction conditions to glycosidation of 2‐azido donor 1 with primary acceptor 2 afforded the desired disaccharide 3 in only 33 % yield with poor stereoselectivity (α/β = 1.6:1, Table , entry 1). This poor yield was on a par with previous results achieved with other unreactive nitrates of the disarmed mannosyl and superdisarmed glucosyl donor series . To improve the utility of this glycosylation reaction, we endeavored to optimize the reaction conditions.…”

“…For our preliminary screening we synthesized 2‐azido‐3,4,6‐tri‐ O ‐benzoyl‐2‐deoxy‐ d ‐galactopyranosyl nitrate 1 by a refined protocol reported herein. According to our previous study, per‐benzylated and per‐benzoylated glycosyl nitrates of the d ‐glucose and d ‐galactose series could be activated efficiently by using a stoichiometric amount of ytterbium(III) trifluoromethanesulfonate [Yb(OTf) 3 ] in Et 2 O/ClCH 2 CH 2 Cl (1,2‐DCE, v/v, 1:1) . However, the application of these reaction conditions to glycosidation of 2‐azido donor 1 with primary acceptor 2 afforded the desired disaccharide 3 in only 33 % yield with poor stereoselectivity (α/β = 1.6:1, Table , entry 1).…”

“…Recently, we discovered that glycosyl nitrates of the d ‐gluco, d ‐galacto‐ and d ‐manno series can be used as effective glycosyl donors for O ‐glycosylation . Lanthanide triflates have been found to be suitable promoters for the activation of nitrate leaving groups of regular oxygenated sugars.…”