Stereodivergent Syntheses of altro and manno Stereoisomers of 2‐Acetamido‐1,2‐dideoxynojirimycin

Abstract

A stereoselective synthesis of 2‐acetamido‐1,2‐dideoxyaltronojirimycin (8) and its manno epimer 9 is described. The synthetic approach is based on key bicyclic carbamate 7, which is easily accessible with high enantiomeric purity on a multigram scale by Sharpless asymmetric epoxidation of 1,4‐pentadien‐3‐ol or 2,4‐pentadien‐1‐ol. This procedure completes an efficient stereodivergent approach to five isomers of 2‐acetamido‐1,2‐dideoxyiminosugars in high overall yields starting from the same key intermediate 7. The approach described in this paper is based on control of the stereoselectivity of the sulfite ring‐opening reaction to give retention of configuration through anchimeric assistance from the endocyclic amine.

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].…”

“…Among these monocyclic iminosugars, a series of pyrrolidines containing acetamide groups which are essential for their β-HexNAcase inhibitions were reported (Figure 2), among which considerable examples were accomplished before the isolation of pochonicine (1) [41,42]. Expectedly, quite a number of these five-membered acetamide derivatives were found to be potent β-HexNAcase inhibitors [16,21,25,26]. In continuation of our interests in structure-activity relationship study of iminosugars [39,[43][44][45][46], in this work, 20 stereoisomeric pyrrolidine analogues of pochonicine (1) were synthesized and systematically assayed as glycosidase inhibitors, in order to look for novel molecules with simplified structure and remained potent inhibitory activities.…”