Stereoselective Synthesis of C-Glycosylated Pyrrolizidines through Nitrone Cycloadditions

High Resolution Image Download MS PowerPoint Slide Polyhydroxylated alkaloids, among which iminosugars represent a prominent subclass, are a structurally diverse family of carbohydrate mimics with significant biological activity. Herein, we report a concise and stereoselective synthesis of five novel C-glycosylated pyrrolizidines ( 15 – 19 ) related to casuarine and hyacinthacines, achieved through 1,3-dipolar cycloadditions of nitrones with E -alkenes. The reactions of nitrone 21 with fructose-derived α,β-unsaturated ester 20a and ketone 20b proceeded with predictable anti-selectivity, affording isoxazolidine intermediates that were transformed into pyrrolizidines via reductive N–O cleavage and subsequent ring closure. Careful stereochemical assignments were established by NOE analyses.