2 research outputs found
Control of Chemo‑, Regio‑, and Enantioselectivity in Copper Hydride Reductions of Morita–Baylis–Hillman Adducts
Nonracemically
ligated copper hydride can be used to effect tandem
S<sub>N</sub>2′/1,2-reductions of racemic Morita–Baylis–Hillman
(MBH) acetates to access enantioenriched chiral allylic alcohols with
defined olefin geometry. MBH esters, including those with β-substitution,
can be transformed to stereodefined enoates by taking advantage of
a bulky, oligomeric, in situ generated trialkoxysiloxane leaving group.
Finally, an atypical conversion of easily arrived at MBH alcohol derivatives
to nonracemic allylic alcohols is disclosed
Discovery of Small-Molecule Enhancers of Reactive Oxygen Species That are Nontoxic or Cause Genotype-Selective Cell Death
Elevation
of reactive oxygen species (ROS) levels has been observed
in many cancer cells relative to nontransformed cells, and recent
reports have suggested that small-molecule enhancers of ROS may selectively
kill cancer cells in various <i>in vitro</i> and <i>in vivo</i> models. We used a high-throughput screening approach
to identify several hundred small-molecule enhancers of ROS in a human
osteosarcoma cell line. A minority of these compounds diminished the
viability of cancer cell lines, indicating that ROS elevation by small
molecules is insufficient to induce death of cancer cell lines. Three
chemical probes (BRD5459, BRD56491, BRD9092) are highlighted that
most strongly elevate markers of oxidative stress without causing
cell death and may be of use in a variety of cellular settings. For
example, combining nontoxic ROS-enhancing probes with nontoxic doses
of l-buthionine sulfoximine, an inhibitor of glutathione
synthesis previously studied in cancer patients, led to potent cell
death in more than 20 cases, suggesting that even nontoxic ROS-enhancing
treatments may warrant exploration in combination strategies. Additionally,
a few ROS-enhancing compounds that contain sites of electrophilicity,
including piperlongumine, show selective toxicity for transformed
cells over nontransformed cells in an engineered cell-line model of
tumorigenesis. These studies suggest that cancer cell lines are more
resilient to chemically induced increases in ROS levels than previously
thought and highlight electrophilicity as a property that may be more
closely associated with cancer-selective cell death than ROS elevation