The first synthesis of a borylated α-methylene-γ-butyrolactone

P. Veeraraghavan Ramachandran, Daniel R. Nicponski, Michael P. Drolet, C. Max Schmidt, Michele T. Yip-Schneider

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Background: The Michael acceptor scaffolding is a source of rich biological activity for α-methylene-γ-butyrolactones and their derivatives. A wide variety of these structures are present in many natural products that are well-known for their useful medicinal properties. Results: The first example of a borylated α-methylene-γ-butyrolactone is presented herein, along with its antipancreatic cancer activities against Panc-1, MIA PaCa-2 and BXPC-3. The synthetic route chosen allows for a wide range of lactones to be synthesized through different cross-coupling reactions starting from arylic bromide precursors. The precursors were synthesized by way of a highly efficient, chemoselective and indium-promoted Barbier reaction. Specifically, the indium metal reacted with only one of two present bromide functionalities: an allylic bromide in the presence of an arylic one. The bromide precursors were also tested for activity in the same bioassay as the borylated lactone and parthenolide. Conclusion: Notably, these brominated compounds demonstrate a significantly higher level of activity than parthenolide.

Original languageEnglish (US)
Pages (from-to)633-639
Number of pages7
JournalFuture Medicinal Chemistry
Volume5
Issue number6
DOIs
StatePublished - Apr 1 2013

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

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