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Updated: May 12, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
The first synthesis of a borylated α-methylene-γ-butyrolactone
P Veeraraghavan Ramachandran1, Daniel R Nicponski, Michael P Drolet
1Herbert C Brown Center for Borane Research, Department of Chemistry, Purdue University, West Lafayette, IN 47907-2084, USA.
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.
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