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

• Published in: European journal of organic chemistry Vol. 2017; no. 47; pp. 7179 - 7185
• Main Authors: de la Fuente, Alex, Verdaguer, Xavier, Riera, Antoni
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 22.12.2017; Wiley Subscription Services, Inc; Wiley-VCH
• Subjects: Asymmetric synthesis; Carbohydrates; Chemistry; Chemistry, Organic; Disseny de medicaments; Drug design; Enzyme inhibitors; Epoxidation; Iminosugars; Inhibidors enzimàtics; Isomers; Neighboring‐group effects; Physical Sciences; Science & Technology; Stereoselectivity; Total synthesis; Carbohydrates; BETA-HEXOSAMINIDASE INHIBITOR; Iminosugars; ENANTIOSELECTIVE RING EXPANSION; PHARMACOLOGICAL CHAPERONES; C-GLYCOSIDES; GLYCOSIDASE INHIBITORS; FABRY DISEASE; Total synthesis; Asymmetric synthesis; BIOLOGICAL EVALUATION; TAY-SACHS; O-GLCNACASE; Neighboring-group effects
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201701282

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. The altro and manno isomers (8 and 9) of 2‐acetamido‐1,2‐dideoxynojirimycin have been synthesized from key intermediate 7. The key step was the stereoselective sulfite ring‐opening with retention of configuration due to the anchimeric effect of the endocyclic amine.