Herbert C Brown Center for Borane Research, Department of Chemistry, Purdue University, West Lafayette, IN 47907-2084, USA.
Future Med Chem. 2013 Apr;5(6):633-9. doi: 10.4155/fmc.13.37.
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.
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.
Notably, these brominated compounds demonstrate a significantly higher level of activity than parthenolide.
迈克尔受体支架是α-亚甲基-γ-丁内酯及其衍生物具有丰富生物活性的来源。许多天然产物中都存在各种各样的这些结构，这些天然产物以其有用的药用特性而闻名。
本文首次提出了硼酸化的α-亚甲基-γ-丁内酯的例子，以及其对 Panc-1、MIA PaCa-2 和 BXPC-3 的抗胰腺癌活性。所选择的合成路线允许通过不同的交叉偶联反应从芳基溴代物前体合成广泛的内酯。前体是通过高效、选择性和铟促进的 Barbier 反应合成的。具体来说，铟金属只与两个溴官能团之一反应：在芳基溴存在的情况下与烯丙基溴反应。硼酸化内酯和冬凌草内酯同样的生物测定也测试了溴化物前体的活性。
值得注意的是，这些溴化化合物的活性明显高于冬凌草内酯。
