Synthesis of pyrrolidine-based analogues of 2-acetamidosugars as N-acetyl-d-glucosaminidase inhibitors

Abstract

A ring-contraction strategy applied to β-azido,γ-hydroxyazepanes yielded after functional group manipulation new tetrahydroxylated pyrrolidines displaying an acetamido moiety, one of these iminosugars demonstrating low micromolar inhibition on N-acetylglucosaminidases.

Synthesis of Pyrrolidine Monocyclic Analogues of Pochonicine and Its Stereoisomers: Pursuit of Simplified Structures and Potent β-N-Acetylhexosaminidase Inhibition

“…The N-acetylamino group is the common structural feature that distinguishes these natural products from the other iminosugars [14]. A diverse range of potent synthetic β-HexNAcase iminosugar inhibitors have been reported including pyrrolidines (4 [15][16][17], 5 [18,19], 6 [20,21] and 7 [22]), piperidines (8 [23,24], 9 [25] and 10 [26]), azepanes (11 [27-29]) and azetidines (12 [30] and 13 [31]); almost all of them contain an N-acetylamino group ( Figure 2) [32]. The novel structure and inhibition properties of pochonicine (1) led to the rapid report of total syntheses [2], together with its enantiomer [33] and analogues [34].…”