Facile synthesis of bisphosphine monoxides from Morita–Baylis–Hillman carbonates

<p>A facile two-step synthesis of bisphosphine monoxides (BPMOs, with both the phosphine and phosphine oxide moieties within one molecule) from readily available Morita–Baylis–Hillman (MBH) carbonates was realized. Under the catalysis of DABCO, the MBH carbonates undergo allylic phosphorylation reaction with diphenylphosphine oxide or diethyl phosphonate to give monophosphine oxides bearing an activated alkene moiety; subsequent base-catalyzed hydrophosphination of the prepared monophosphine oxide with HPPh₂ readily affords the BPMOs.</p

Photochemical Hydrogen Atom Transfer Catalysis for Dehydrogenation of Alcohols To Form Carbonyls

Controllable oxidation of alcohols to carbonyls is one of the fundamental transformations in organic chemistry. Herein, we report an unprecedented visible-light-mediated metal-free oxidation of alcohols to carbonyls with hydrogen evolution. By synergistic combination of organophotocatalyst 4CzIPN and a thiol hydrogen atom transfer catalyst, a broad range of alcohols, including primary and secondary benzylic alcohols as well as aliphatic alcohols, were readily oxidized to carbonyls in moderate to excellent yields. A site-selective oxidation has also been achieved by this protocol. Mechanistic investigation indicates that the oxidation proceeds through an oxidative radical–polar crossover process to obtain an α-oxy carbon cation

Chemoselective P(NMe₂)₃‑Mediated Reductive Epoxidation between Two Different Carbonyl Electrophiles: Synthesis of Highly Functionalized Unsymmetrical Epoxides

Herein, we report a chemoselective P­(NMe₂)₃-mediated reductive epoxidation of α-dicarbonyl compounds such as isatins, α-keto esters, and α-diketones with aldehydes and ketones, leading to an efficient synthesis of a wide range of highly functionalized unsymmetrical epoxides in moderate to excellent yields and diastereoselectivities. The Kukhtin–Ramirez adduct, which is exclusively generated in situ from an α-dicarbonyl compound and P­(NMe₂)₃, plays a key role in governing the chemoselectivity. It represents the first practical synthesis of unsymmetrical epoxides via direct reductive epoxidation of two different carbonyl electrophiles and also complements the existing methods of generating epoxides

Chemoselective P(NMe₂)₃‑Mediated Reductive Epoxidation between Two Different Carbonyl Electrophiles: Synthesis of Highly Functionalized Unsymmetrical Epoxides

Herein, we report a chemoselective P­(NMe₂)₃-mediated reductive epoxidation of α-dicarbonyl compounds such as isatins, α-keto esters, and α-diketones with aldehydes and ketones, leading to an efficient synthesis of a wide range of highly functionalized unsymmetrical epoxides in moderate to excellent yields and diastereoselectivities. The Kukhtin–Ramirez adduct, which is exclusively generated in situ from an α-dicarbonyl compound and P­(NMe₂)₃, plays a key role in governing the chemoselectivity. It represents the first practical synthesis of unsymmetrical epoxides via direct reductive epoxidation of two different carbonyl electrophiles and also complements the existing methods of generating epoxides

Still in Search for an EAAT Activator: GT949 Does Not Activate EAAT2, nor EAAT3 in Impedance and Radioligand Uptake Assays

Excitatory amino acid transporters (EAATs) are important regulators of amino acid transport and in particular glutamate. Recently, more interest has arisen in these transporters in the context of neurodegenerative diseases. This calls for ways to modulate these targets to drive glutamate transport, EAAT2 and EAAT3 in particular. Several inhibitors (competitive and noncompetitive) exist to block glutamate transport; however, activators remain scarce. Recently, GT949 was proposed as a selective activator of EAAT2, as tested in a radioligand uptake assay. In the presented research, we aimed to validate the use of GT949 to activate EAAT2-driven glutamate transport by applying an innovative, impedance-based, whole-cell assay (xCELLigence). A broad range of GT949 concentrations in a variety of cellular environments were tested in this assay. As expected, no activation of EAAT3 could be detected. Yet, surprisingly, no biological activation of GT949 on EAAT2 could be observed in this assay either. To validate whether the impedance-based assay was not suited to pick up increased glutamate uptake or if the compound might not induce activation in this setup, we performed radioligand uptake assays. Two setups were utilized; a novel method compared to previously published research, and in a reproducible fashion copying the methods used in the existing literature. Nonetheless, activation of neither EAAT2 nor EAAT3 could be observed in these assays. Furthermore, no evidence of GT949 binding or stabilization of purified EAAT2 could be observed in a thermal shift assay. To conclude, based on experimental evidence in the present study GT949 requires specific assay conditions, which are difficult to reproduce, and the compound cannot simply be classified as an activator of EAAT2 based on the presented evidence. Hence, further research is required to develop the tools needed to identify new EAAT modulators and use their potential as a therapeutic target