Stereoselective Synthesis of C‑Glycosylated Pyrrolizidines through Nitrone Cycloadditions

通过硝酮环加成反应立体选择性合成C-糖基化吡咯烷

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Abstract

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.

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