ABSTRACT
Preparation of α-anomeric derivatives of 2-acetamido-2-deoxy-d-glucopyranosides through Koenigs–Knorr reaction is complicated by the facile formation of β-glycosides or 1,2-oxazolines due to neighboring group participation of the N-acetylamino group. 1 Nonparticipating groups at position 2, such as the azido group, have been used to generate preferentially α-glycosides, albeit multistep transformations are then needed for the introduction of the azido group and subsequent conversion into the N-acetylamino group. 2 Alternatively, ring-fused 2,3-oxazolidinone derivatives have recently been utilized to obtain α-glycosides in good yields, again requiring suitable protecting group transformations. 3 For simple glycosides, however, a Fischer-type glycosidation of 1 provides a straightforward method. 4 ω-Azidoalkyl derivatives are of general interest as functional spacer derivatives, allowing for click chemistry methodology as well as for conversion into terminal amino groups to be used for the preparation of dendrimers and neoglycoconjugates. 5 As an alternative to the classical Fischer glycosidation, the more convenient use of acidic ion-exchange resin was tested. 6 It resulted in the formation of variable mixtures of α/β glycosides. In order to generate pure α glycoside, the anomeric mixture was subjected to peracetylation followed by chromatography on silica gel, which allowed the removal of the undesired β-anomer and gave compound 2 in 54% yield (without further separation of mixed fractions). The subsequent steps comprised the nucleophilic displacement of the chlorine in 2 by azide ion, giving 3. Due to similar mobility of 2 and 3 on TLC, the reaction was monitored by NMR analysis. Since partial de-O-acetylation was observed in the course of the reaction, the crude product was acetylated to give 3 in 92% yield. Following Zemplén transesterification afforded crystalline compound 4 in 96% yield.
