Conformationally Restricted Oxazolidin‐2‐one Fused Bicyclic Iminosugars as Potential Glycosidase Inhibitors. Issue 38 (5th October 2020)

• Record Type: Journal Article
• Authors: Domingues, Maria; Jaszczyk, Justyna; Ismael, Maria Isabel; Figueiredo, José Albertino; Daniellou, Richard; Lafite, Pierre; Schuler, Marie; Tatibouët, Arnaud
• Is Part Of: European journal of organic chemistry. Issue 38(2020)
• Page Start: 6109
• Page End: 6126
• Publication Date: 2020-10-05
• Subjects: Iminosugar -- Oxazolidinone -- Oxazolidinethione -- Glycosidase inhibitor; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.202001053
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract : The synthesis of fused bicyclic oxazolidin‐2‐one (OZO) iminosugars was achieved through a tandem Staudinger reduction/retro‐Michael/intramolecular Michael addition from the corresponding OZO azidosugars. Those precursors, based on both aldopentofuranoses and ketofuranohexoses backbones, were obtained following alkylation and oxidation of the related oxazolidine‐2‐thione (OZT) azidosugars. Eight OZO based iminosugars were isolated in good yields and evaluated for their potency as glycosidases inhibitors, thus extending the family of known 1‐Deoxynojirimycin (DNJ) bicyclic analogues. Abstract : The synthesis of unprecedented bicyclic oxazolidin‐2‐one (OZO) fused iminosugars is described. The key step involves a tandem Staudinger/retro Michael/aza Michael sequence from OZO azidosugars, themselves obtained through oxidation of oxazolidin‐2‐thione (OZT) precursors. The iminosugars were subsequently evaluated as glycosidase inhibitors.