Asymmetric 2,4-Dienylation/[4 + 2] Annulation Cascade to Construct Fused Frameworks via Auto-Tandem Palladium Catalysis.

A palladium catalyzed tandem reaction between ortho-functionalized aryl enones and 2,4-dienyl carbonates has been presented, proceeding through sequential 2,4-dienylation/Michael addition/π-σ-π isomerization/allylic alkylation. A broad array of enantioenriched architectures having fused and spirocyclic frameworks are constructed in moderate to excellent yields and stereoselectivity. Notably, the intrinsic intramolecular Diels-Alder reaction pattern of the dienylated intermediates is well reversed via Pd(0)-π-Lewis base catalysis.

Major royal jelly proteins alleviate non-alcoholic fatty liver disease in mice model by regulating disordered metabolic pathways.

Nonalcoholic fatty liver disease (NAFLD), the major cause of global chronic hepatic injury, has obtained increasing attention while the current drug treatment still laid safety hazards. Major royal jelly proteins (MRJPs), the water-soluble proteins enriched in royal jelly (RJ), were applied to study its effects on improving NAFLD in the NAFLD mouse model. Herein, we demonstrated that intaking of 250-500 mg/kg/day MRJPs significantly decreased the rate of obesity, dyslipidemia, hepatic steatosis, and insulin resistance. Next, TOF to MRM ("TM") widely targeted metabolomics (untargeted metabolomics + widely targeted metabolomics) was further used to explore the potential mechanism, and we found that 500 mg/kg MRJPs alleviated lipid metabolism, oxidative stress, and inflammation mainly by regulating the metabolisms of alpha-linolenic acid, linoleic acid, arachidonic acid, and biosynthesis of unsaturated fatty acids. Moreover, by detecting multiple oxidative stress factors and inflammatory cytokines, we found that MRJPs indeed exerted antioxidant and anti-inflammatory effects. Together, we demonstrated that MRJPs could mediate the progress of NAFLD through the "multi-component-multi-target-multi-pathway" mechanism, which could be considered as an ideal functional food in alleviating NAFLD. PRACTICAL APPLICATIONS: Royal jelly (RJ) is a bee product with high nutritional value. Major royal jelly proteins (MRJPs) are water-soluble proteins in RJ. Our research showed that MRJPs significantly ameliorated NAFLD induced by a high-fat diet in mice, suggesting that MRJPs could be used as an active ingredient to help improve NAFLD, which was beneficial for the development of related functional foods and the economic value of RJ. Moreover, the metabolic pathways involved in the ameliorative effect of MRJPs were investigated, which provided new ideas for the prevention and treatment of NAFLD.

Asymmetric Auto-Tandem Palladium Catalysis for 2,4-Dienyl Carbonates: Ligand-Controlled Divergent Synthesis.

Developing new asymmetric auto-tandem catalysis processes, especially in a divergent manner, is highly attractive but extremely challenging. Presented herein is a palladium-catalyzed auto-tandem reaction between 2,4-dienyl carbonates and o-TsNH arylimines or trifluoroacetophenones that proceeds through a consecutive N-allylation, vinylogous addition, π-σ-π isomerization, and another N-allylation sequence. Importantly, switchable diastereodivergent synthesis could be achieved by tuning the chiral bisphosphine ligands, which led to the construction of a broad spectrum of fused tetrahydroquinoline architectures with moderate to excellent enantioselectivity. Ligand control even enabled effective access to regiodivergent azetidine or chemodivergent ß-H elimination with fair enantioselectivity, further showing the versatility of the current auto-tandem catalysis.

A Palladium Complex as an Asymmetric π-Lewis Base Catalyst for Activating 1,3-Dienes.

Here we report that palladium(0) complexes can coordinate in a η2 fashion to 1,3-dienes and significantly raise the energy of their highest occupied molecular orbital (HOMO) by donating the electrons from the d-orbitals to the empty antibonding molecular orbitals of double bonds (π*) via back-bonding. Thus, the uncoordinated double bond, as a more reactive partner on the basis of the principle of vinylogy, can directly attack imines, furnishing a formal hydrodienylation reaction enantioselectively. A chemoselective cascade vinylogous addition/allylic alkylation difunctionalization process between 1,3-dienes and imines with a nucleophilic group is also compatible, by trapping in situ formed π-allylpalladium species after initial ene addition. This π-Lewis base catalytic mode, featuring simple η2coordination, vinylogous activation, and compatibility with both conjugated neutral polyenes and electron-deficient polyenes, is elucidated by control experiments and density functional theory (DFT) calculations.