A Photochemical One-Pot Three-Component Synthesis of Tetrasubstituted Imidazoles

Tetrasubstituted imidazoles can be formed in a photochemical one-pot synthesis from aldehydes, α-aminonitriles, and isoxazoles. Condensation of the first two components produces α-(alkylideneamino)­nitriles which react under basic conditions with the acylazirines formed in situ by photochemical ring transformation of the isoxazole component. This process includes an unusual cleavage of the C²–C³ bond of the acylazirine. The reaction mechanism was studied by DFT calculations

A Light-Induced Vinylogous Nazarov-Type Cyclization

The first examples of a photochemically induced vinylogous Nazarov-type cyclization forming a cycloheptadienone core are described. The reaction can be included in a three-step cascade consisting of a photochemical isoxazole–azirine ring contraction, cobalt­(II)-catalyzed ring expansion, and the photochemical cyclization. Furthermore, the first representative of the hitherto unknown 1-azatricyclo­[2.2.0.0^2,6]­hexanes has been identified as a side product of the azirine formation

A Photoinduced Cobalt-Catalyzed Synthesis of Pyrroles through <i>in Situ</i>-Generated Acylazirines

Tetrasubstituted pyrroles can be synthesized in a one-pot procedure from isoxazoles. The process includes the photoinduced <i>in situ</i> formation of acylazirines combined with a subsequent cobalt­(II)-catalyzed ring expansion with 1,3-diketones

A Light-Induced Vinylogous Nazarov-Type Cyclization

The first examples of a photochemically induced vinylogous Nazarov-type cyclization forming a cycloheptadienone core are described. The reaction can be included in a three-step cascade consisting of a photochemical isoxazole–azirine ring contraction, cobalt­(II)-catalyzed ring expansion, and the photochemical cyclization. Furthermore, the first representative of the hitherto unknown 1-azatricyclo­[2.2.0.0^2,6]­hexanes has been identified as a side product of the azirine formation

A Photoinduced Cobalt-Catalyzed Synthesis of Pyrroles through <i>in Situ</i>-Generated Acylazirines

Tetrasubstituted pyrroles can be synthesized in a one-pot procedure from isoxazoles. The process includes the photoinduced <i>in situ</i> formation of acylazirines combined with a subsequent cobalt­(II)-catalyzed ring expansion with 1,3-diketones

Inhibitors of Mutant Isocitrate Dehydrogenases 1 and 2 (mIDH1/2): An Update and Perspective

Isocitrate dehydrogenases 1 and 2 (IDH1/2) are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid cycle. However, mutant IDH1/2 (mIDH1/2) reduces α-KG to the oncometabolite 2-hydroxyglutarate (2-HG). High levels of 2-HG competitively inhibit the α-KG-dependent dioxygenases involved in histone and DNA demethylation, thereby impairing normal cellular differentiation and promoting tumor development. Thus, small molecules that inhibit these mutant enzymes may be therapeutically beneficial. Recently, an increasing number of mIDH1/2 inhibitors have been reported. In this review, we summarize the molecular basis of mIDH1/2 and the activity, binding modes, and progress in clinical application of mIDH1/2 inhibitors. We note important future research directions for mIDH1/2 inhibitors and discuss potential therapeutic strategies for the development of mIDH1/2 inhibitors to treat IDH1/2 mutated tumors

Mechanism and <i>cis</i>/<i>trans</i> Selectivity of Vinylogous Nazarov-type [6π] Photocyclizations

Vinylogous Nazarov-type cyclizations yield seven-membered rings from butadienyl vinyl ketones via a photochemical [6π] photocyclization followed by subsequent isomerization steps. The mechanism of this recently developed method was investigated using unrestricted DFT, SF-TDDFT, and CASSCF/NEVPT2 calculations, suggesting three different pathways that lead either to pure <i>trans</i>, pure <i>cis</i>, or mixed <i>cis</i>/<i>trans</i> configured products. Singlet biradicals or zwitterions occur as intermediates. The computational results are supported by deuterium-labeling experiments

Phenotype of <i>fbl17</i> pollen at anther dehiscence.

<p>Pollen from dehiscent anthers of WT and fbl17 ^+/− plants was stained with DAPI and observed under UV illumination. n = total number. Normal pollen all showed two sperm cells. Abnormal pollen showed a single sperm-like cell.</p

<i>fbl17</i> T-DNA insertion mutants.

<p>(A) FBL17 transcript accumulation in plants over-expressing the E2Fa transcription factor and its dimerization partner, DPa. Quantitative RT-PCR on RNA extracted from E2Fa-DPa overexpressing (OE) seedlings show a 15-fold increase in the relative abundance of <i>FBL17</i> transcript compared to control RNA (Col-0). The experiment was three times repeated. Data are means±SE. (B) Diagram of the genomic locus of FBL17. The two T-DNA insertions disrupt the 7^th exon and the 6^th intron in the <i>fbl17-1</i> and <i>fbl17-2</i> allele respectively. Light grey filling indicate non-translated region of the transcript whereas dark grey filling indicates coding sequence. (C) Wild type silique opened to reveal the seed content. (D) Heterozygous <i>fbl17-1^+/−</i> silique displaying a reduced fertility and aborted seeds (marked by white arrows). (E) Homozygous <i>fbl17-1</i> mutant complemented with the <i>FBL17</i> genomic clone show wild type siliques and normal seed development. (C, D, E, bar = 500 µm).</p

Genetic analysis of <i>fbl17</i> mutant plants.

<p>Resistance to sulfadiazine (Sulf^R, sulfadiazine resistant seedlings; Sulf^S, sulfadiazine sensitive seedlings) was used for the <i>AtFbl17-1</i> and <i>AtFbl17-2</i> plants. n = total number. Transmission efficiencies were calculated according to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004780#pone.0004780-Howden1" target="_blank">[59]</a>: TE = Sulf^R/Sulf^S×100%.</p