title: The first synthesis of a borylated α-methylene-γ-butyrolactone.
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.
  
  
  CONCLUSIONS
  Notably, these brominated compounds demonstrate a significantly higher level of activity than parthenolide.
authors.affiliation: Herbert C Brown Center for Borane Research, Department of Chemistry, Purdue University, West Lafayette, IN 47907-2084, USA.
authors.forename: P Veeraraghavan
authors.initials: PV
authors.lastname: Ramachandran
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Nicponski
authors.forename: Michael P
authors.initials: MP
authors.lastname: Drolet
authors.forename: C Max
authors.initials: CM
authors.lastname: Schmidt
authors.forename: Michele T
authors.initials: MT
authors.lastname: Yip-Schneider
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002384:Catalysis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D054879:Halogenation; D006801:Humans; D010165:Palladium / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; C014096:alpha-methylene gamma-butyrolactone; D010165:Palladium; D015107:4-Butyrolactone