3 research outputs found
El Diario de Pontevedra : periódico liberal: Ano XXVII Número 7742 - 1910 marzo 1
CopperÂ(II) aryl species are proposed
key intermediates in Cu-catalyzed
cross-coupling reactions. Novel three-coordinate copperÂ(II) aryls
[Cu<sup>II</sup>]-C<sub>6</sub>F<sub>5</sub> supported by ancillary
β-diketiminate ligands form in reactions between copperÂ(II)
alkoxides [Cu<sup>II</sup>]-O<sup><i>t</i></sup>Bu and BÂ(C<sub>6</sub>F<sub>5</sub>)<sub>3</sub>. Crystallographic, spectroscopic,
and DFT studies reveal geometric and electronic structures of these
CuÂ(II) organometallic complexes. Reaction of [Cu<sup>II</sup>]-C<sub>6</sub>F<sub>5</sub> with the free radical NO<sub>(g)</sub> results
in C-N bond formation to give [Cu]Â(η<sup>2</sup>-ONC<sub>6</sub>F<sub>5</sub>). Remarkably, addition of the phenolate anion
PhO<sup>–</sup> to [Cu<sup>II</sup>]-C<sub>6</sub>F<sub>5</sub> directly affords diaryl ether PhO-C<sub>6</sub>F<sub>5</sub> with
concomitant generation of the copperÂ(I) species [Cu<sup>I</sup>]Â(solvent)
and {[Cu<sup>I</sup>]-C<sub>6</sub>F<sub>5</sub>}<sup>−</sup>. Experimental and computational analysis supports redox disproportionation
between [Cu<sup>II</sup>]-C<sub>6</sub>F<sub>5</sub> and {[Cu<sup>II</sup>]Â(C<sub>6</sub>F<sub>5</sub>)Â(OPh)}<sup>−</sup> to give {[Cu<sup>I</sup>]-C<sub>6</sub>F<sub>5</sub>}<sup>−</sup> and [Cu<sup>III</sup>]Â(C<sub>6</sub>F<sub>5</sub>)Â(OPh) unstable
toward reductive elimination to [Cu<sup>I</sup>]Â(solvent) and
PhO-C<sub>6</sub>F<sub>5</sub>
Evaluation of Difluoromethyl Ketones as Agonists of the γ‑Aminobutyric Acid Type B (GABA<sub>B</sub>) Receptor
The design, synthesis, biological
evaluation, and in vivo studies
of difluoromethyl ketones as GABA<sub>B</sub> agonists that are not
structurally analogous to known GABA<sub>B</sub> agonists, such as
baclofen or 3-aminopropyl phosphinic acid, are presented. The difluoromethyl
ketones were assembled in three synthetic steps using a trifluoroacetate-release
aldol reaction. Following evaluation at clinically relevant GABA receptors,
we have identified a difluoromethyl ketone that is a potent GABA<sub>B</sub> agonist, obtained its X-ray structure, and presented preliminary
in vivo data in alcohol-preferring mice. The behavioral studies in
mice demonstrated that this compound tended to reduce the acoustic
startle response, which is consistent with an anxiolytic profile.
Structure–activity investigations determined that replacing
the fluorines of the difluoromethyl ketone with hydrogens resulted
in an inactive analogue. Resolution of the individual enantiomers
of the difluoromethyl ketone provided a compound with full biological
activity at concentrations less than an order of magnitude greater
than the pharmaceutical, baclofen
Evaluation of Difluoromethyl Ketones as Agonists of the γ‑Aminobutyric Acid Type B (GABA<sub>B</sub>) Receptor
The design, synthesis, biological
evaluation, and in vivo studies
of difluoromethyl ketones as GABA<sub>B</sub> agonists that are not
structurally analogous to known GABA<sub>B</sub> agonists, such as
baclofen or 3-aminopropyl phosphinic acid, are presented. The difluoromethyl
ketones were assembled in three synthetic steps using a trifluoroacetate-release
aldol reaction. Following evaluation at clinically relevant GABA receptors,
we have identified a difluoromethyl ketone that is a potent GABA<sub>B</sub> agonist, obtained its X-ray structure, and presented preliminary
in vivo data in alcohol-preferring mice. The behavioral studies in
mice demonstrated that this compound tended to reduce the acoustic
startle response, which is consistent with an anxiolytic profile.
Structure–activity investigations determined that replacing
the fluorines of the difluoromethyl ketone with hydrogens resulted
in an inactive analogue. Resolution of the individual enantiomers
of the difluoromethyl ketone provided a compound with full biological
activity at concentrations less than an order of magnitude greater
than the pharmaceutical, baclofen