Synthesis of novel migrastatin and dorrigocin A analogues from D-glucal

Guillaume Anquetin, Sarah L. Rawe, Kevin McMahon, Evelyn P. Murphy, Paul V. Murphy

Research output: Contribution to journalArticlepeer-review

Abstract

The synthesis of a range of analogues of the migrastatin macrolide core has been achieved from tri-O-acetyl-D-glucal in order to facilitate structure-activity studies. Efficient macrolactone formation was achieved in the presence of a reactive olefin, by increasing steric hindrance in the olefin environment. Acyclic analogues of migrastatin, structurally related to dorrigocin A, have also been prepared from D-glucal. The dorrigocin A analogues were prepared using the combination of the cross metathesis of ethyl 6-heptenoate with a glycal derivative and a subsequent allylic rearrangement-alkene isomerisation reaction (Perlin reaction). A synthetic route is thus provided that will enable dorrigocin A analogues to be prepared in parallel to migrastatin analogues in the search for novel anti-cancer and anti-arthritic therapeutics. Biological evaluation of one migrastatin and one dorrigocin A sugar derived analogue show that they inhibit proliferation and serum-induced migration of tumour and synovial cells at higher concentrations than evodiamine. Dorrigocin A analogues displayed similar potency to analogues of the migrastatin core.

Original languageEnglish
Pages (from-to)1592-1600
Number of pages9
JournalChemistry - A European Journal
Volume14
Issue number5
DOIs
Publication statusPublished - 8 Feb 2008
Externally publishedYes

Keywords

  • Allylic rearrangement
  • Cancer
  • Carbohydrates
  • Metathesis
  • Natural products

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