Fused vs. spiro: Kinetic,not thermodynamic preference may direct the reaction of α-carbonyl oxonium ylides

Rh(II)-catalyzed decomposition of certain cyclic α-diazocarbonyl compounds in the presence of cyclic ethers has been shown to give bicyclic ring expansion products. These are thought to arise from a [1,4]-alkyl shift toward the carbonyl oxygen atom and are in contrast with the recently observed spirocyclic products of a Stevens-type [1,2]-alkyl shift within the postulated oxonium ylide intermediate. Quantum chemical calculations performed at the B3LYP/6-31G* level of theory showed that the former reaction pathway (toward fused bicycles) is kinetically preferred.     

Synthesis and conformational investigation of tetrapeptide analogues of the fragment B23-B26 of insulin

Tetrapeptides containing one of a set of four different α,α-dialkyl glycines at the C-terminus were synthesized by conventional methods in solution and their conformational behavior investigated by ¹H NMR spectroscopy in connection with molecular mechanics calculations. The results were consistent with conformations stabilized by a γ-turn in the case of compounds with alkyl groups larger than methyl, while the corresponding Aib derivative did not exhibit intramolecular hydrogen bonding.     

First-principles study on the origin of optical transitions to be associated with F colour centers for PbWO4 crystals

The electronic structures of PbWO₄ crystals containing F type color centers with the lattice structure optimized are studied within the framework of the fully relativistic self-consistent Direc–Slater theory, using a numerically discrete variational (DV-Xα) method. The calculated results show that F and F⁺ centers have donor energy level in forbidden band. Their optical transition energy are 1.84 eV, 2.21 eV, respectively, which corresponds to the 680 nm, 550 nm absorption bands. It predicts that the 680 nm, 550 nm absorption bands originate form the F and F⁺ centers in PbWO₄ crystals.     

Generalized 3G theorem and application to relativistic stable process on non-smooth open sets

Let G(x,y) and GD(x,y) be the Green functions of rotationally invariant symmetric α-stable process in Rd and in an open set D, respectively, where 0<α<2. The inequality GD(x,y)GD(y,z)/GD(x,z)?c(G(x,y)+G(y,z)) is a very useful tool in studying (local) Schrödinger operators. When the above inequality is true with c=c(D)∈(0,∞), then we say that the 3G theorem holds in D. In this paper, we establish a generalized version of 3G theorem when D is a bounded κ-fat open set, which includes a bounded John domain. The 3G we consider is of the form GD(x,y)GD(z,w)/GD(x,w), where y may be different from z. When y=z, we recover the usual 3G. The 3G form GD(x,y)GD(z,w)/GD(x,w) appears in non-local Schrödinger operator theory. Using our generalized 3G theorem, we give a concrete class of functions belonging to the non-local Kato class, introduced by Chen and Song, on κ-fat open sets. As an application, we discuss relativistic α-stable processes (relativistic Hamiltonian when α=1) in κ-fat open sets. We identify the Martin boundary and the minimal Martin boundary with the Euclidean boundary for relativistic α-stable processes in κ-fat open sets. Furthermore, we show that relative Fatou type theorem is true for relativistic stable processes in κ-fat open sets. The main results of this paper hold for a large class of symmetric Markov processes, as are illustrated in the last section of this paper. We also discuss the generalized 3G theorem for a large class of symmetric stable Lévy processes.     

Direct, organocatalytic α-sulfenylation of aldehydes and ketones

A method for direct sulfenylation of aldehydes and ketones, catalyzed by a novel pyrrolidine trifluoromethanesulfonamide organocatalyst, has been developed. This process serves as an efficient and mild approach to the preparation of α-phenylthio-ketones and -aldehydes.     

New catalytic effect of thiourea on the oxidative cyanation of N-aryltetrahydroisoquinolines

Thiourea itself has been introduced as a mild and efficient organocatalyst for the oxidative α -cyanation of N-aryltetrahydroisoquinolines (THIQs) with trimethylsilyl cyanide (TMSCN), giving the corresponding products in good to excellent yields. Experimental investigations demonstrated that thiourea acts as a radical initiator by abstracting hydroxyl radical (OH) from tert-butyl hydroperoxide (TBHP) directly instead of non-covalent hydrogen bondings (H-bondings) activation. The use of thiourea as a radical initiator offers a new avenue for innovative chemical transformations in organocatalyzed radical chemistry.     

Synthesis of new α,α,β,β-tetrafluoroesters

Substituted phenyl iodides or diiodides reacted with ethyl iodotetrafluoroproponylate ICF₂CF₂CO₂Et, 1 in the presence of copper powder to give the coupled products 2 or 3 in good yields. Addition of 1 to ethylene and allyl acetate proceeded smoothly under thermal and radical conditions to give the corresponding adducts, which underwent elimination reaction to give β-vinyl and β-allyl α,α,β,β-tetrafluoroesters, CH₂CHCF₂CF₂CO₂Et, 4 and CH₂CHCH₂CF₂CF₂CO₂Et, 5, respectively. 1 also readily reacted with 1,5-hexadiene and 1-hexene with copper or palladium complex, followed by reduction to remove iodine to produce ω-alkenyl-α,α,β,β-tetrafluoroester CH₂CH(CH₂)₄CF₂CF₂CO₂Et 6 and α,α,β,β-tetrafluoroester C₄H₉CH₂CHICF₂CF₂CO₂Et.     

Metabolomic-based investigation of Yinlan alleviating hyperlipidemia by inhibiting blood stasis and phlegm turbidity through the PXR-CYP3A4-ABCB1-FXR pathway

Yinlan lipid regulatory capsule (YL) is a composite traditional Chinese medicine (TCM) new drug to alleviate hyperlipidemia, while its therapeutic mechanism in vivo was not clarified with nontargeted metabolomics investigation. An animal model was established in rats fed a high-fat diet, and their body weights, body mass index (BMI) and blood cholesterol levels were measured. Serum, liver and kidney tissue samples were also extracted for PXR-CYP3A4-ABCB1-FXR signaling pathway research using PCR and UHPLC–MS. The obtained plasma samples were analyzed by UHPLC-Q-TOF-MS metabolomic investigation, which revealed PXR-CYP3A4-related metabolites and changes induced by YL. Finally, the key metabolites were chosen as index components, and their levels in the serum, liver, small intestine and bile were used for simultaneous UHPLC–MS-MS determination. The results indicated that YL was effective in rebalancing blood TG and TC levels (compared to controls). With respect to the PXR-CYP3A4-ABCB1 pathway, as a result of YL’s effect, gene expression or activity of the two targets decreased significantly in both the liver and kidney. The same trend was observed in the serum samples mentioned above. Metabolomics screening and data revealed that 44 metabolites can be regarded as biomarkers related to hyperlipidemia, fatty acids synthesis, and body energy consumption, as well as synthesis, transportation and exertion of cholesterol. YL’s treatment focused on 26 of them, primarily bile acids, indicating that the antihyperlipidemic effect of this drug lies in its inhibitory activity of cholesterol metabolism. Subsequent analysis of those in vivo components revealed that significant increases (compared to the model group) occurred in the blood, liver, small intestine and bile in groups that received medium and high doses of YL (while the low dose was relatively unchanged). Those target components exhibit a close relationship with PXR and/or CYP3A4. The use of YL repressed PXR expression and subsequently decreased CYP3A4 activity. As a result, synthesis of related bile acids increased, while cholesterol levels decreased, consequently leading to the attenuation of hyperlipidemia. This study comprehensively investigated the antihyperlipidemia mechanism of YL based on its repression of PXR-CYP3A4 activity and related metabolite yield, establishing an accurate method for evaluating the therapeutic effect of YL.