Highly chemoselective deoxygenation of N-heterocyclic N-oxides under transition metal-free conditions.

Because their site-selective C-H functionalizations are now considered one of the most useful tools for synthesizing various N-heterocyclic compounds, the highly chemoselective deoxygenation of densely functionalized N-heterocyclic N-oxides has received much attention from the synthetic chemistry community. Here, we provide a protocol for the highly chemoselective deoxygenation of various functionalized N-oxides under visible light-mediated photoredox conditions with Na2-eosin Y as an organophotocatalyst. Mechanistic studies imply that the excited state of the organophotocatalyst is reductively quenched by Hantzsch esters. This operationally simple technique tolerates a wide range of functional groups and allows high-yield, multigram-scale deoxygenation.

Highly Chemoselective Deoxygenation of N-Heterocyclic N-Oxides Using Hantzsch Esters as Mild Reducing Agents.

Herein, we disclose a highly chemoselective room-temperature deoxygenation method applicable to various functionalized N-heterocyclic N-oxides via visible light-mediated metallaphotoredox catalysis using Hantzsch esters as the sole stoichiometric reductant. Despite the feasibility of catalyst-free conditions, most of these deoxygenations can be completed within a few minutes using only a tiny amount of a catalyst. This technology also allows for multigram-scale reactions even with an extremely low catalyst loading of 0.01 mol %. The scope of this scalable and operationally convenient protocol encompasses a wide range of functional groups, such as amides, carbamates, esters, ketones, nitrile groups, nitro groups, and halogens, which provide access to the corresponding deoxygenated N-heterocycles in good to excellent yields (an average of an 86.8% yield for a total of 45 examples).

Potent inhibitions of monoamine oxidase A and B by acacetin and its 7-O-(6-O-malonylglucoside) derivative from Agastache rugosa.

Five compounds were isolated from the leaves of Agastache rugosa and tested for monoamine oxidase (MAO) inhibitory activity. Acacetin, a flavonoid, potently inhibited recombinant human MAO-A and MAO-B (IC50=0.19 and 0.17µM, respectively), and reversibly and competitively inhibited MAO-A and MAO-B (Ki=0.045 and 0.037µM, respectively). Acacetin 7-O-(6-O-malonylglucoside) (AMG) was also found to effectively inhibit MAO-A and MAO-B (IC50=2.34 and 1.87µM, respectively), and to reversibly and competitively inhibit MAO-A and MAO-B (Ki=1.06 and 0.38µM, respectively). Tilianin (a glucoside derivative of acacetin) had little inhibitory activity, but the introduction of a malonyl group at sugar moiety significantly increased inhibitory activity. Molecular docking simulation revealed the binding energy of acacetin for MAO-B (-44.2kcal/mol) was greater than its energy for MAO-A (-27.0kcal/mol), and that the Cys172 residue of MAO-B was important for hydrogen bonding with acacetin. AMG was predicted to bind to MAO-B with an energy of -23.1kcal/mol by possible hydrogen-bond formation between an oxygen atom of Ile477 residue and a hydrogen atom (H17) of AMG. However, the interaction between AMG and MAO-A was not verified by the docking simulation. This study suggests acacetin and AMG be viewed as new reversible MAO inhibitors, and useful lead compounds for the inhibitor development.