Synthesis of the purported structure of glyphaeaside C and proposed revisions to the structures of the glyphaeaside alkaloids

Brendan J Byatt, Atsushi Kato, Stephen G Pyne

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The 10 glyphaeaside alkaloids isolated from the roots of Glyphaea brevis were originally purported as piperidine-based 1-C-alkylated iminosugars, with the A-, B-, and C-type glyphaeasides bearing l-DFJ, DGJ, and DNJ ring configurations, respectively. Subsequent investigations have revealed glyphaeaside C as being a pyrrolidine-based iminosugar with a DMDP ring configuration via total synthesis of the revised structure. In this work, side chain diastereomers of the originally purported structure of glyphaeaside C (10) and two related α-1-C-alkylated DNJ derivatives were synthesized from a common precursor, which was prepared in turn via stereoselective Grignard addition to a protected d-glycosylamine, followed by a reductive amination-cyclization sequence. Glycosidase inhibitory activity studies revealed general structure 10 as having potent inhibition against various α-glucosidases and weak inhibition against almond β-glucosidase in agreement with similar DNJ-based iminosugars and in contrast to natural glyphaeaside C, suggesting that the (1,2-dihydroxy-3-phenyl)propyl moiety does not play a particularly vital role in the inhibitory modes of action of either compound. Furthermore, the absolute configuration of natural glyphaeaside C was proposed as that of d-DMDP, and the structures of the A- and B-type glyphaeasides were revised as 1-deoxy-DALDP and DALDP derivatives, respectively, based on interpretation of their reported NMR spectroscopic data.

Original languageEnglish
Pages (from-to)1261-1273
Number of pages13
JournalJournal of Natural Products
Volume86
Issue number5
DOIs
StatePublished - 2023/05/26

Keywords

  • Enzyme Inhibitors/pharmacology
  • Alkaloids/pharmacology
  • Imino Sugars/chemistry
  • alpha-Glucosidases/metabolism
  • Molecular Structure

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