Chemo-, Regio- and Stereoselective Preparation of (Z)-2-Butene-1,4-Diol Monoesters via Pd-Catalyzed Decarboxylative Acyloxylation.

(Z)-alkenes are useful synthons but thermodynamically less stable than their (E)-isomers and typically more difficult to prepare. The synthesis of 1,4-hetero-bifunctionalized (Z)-alkenes is particularly challenging due to the inherent regio- and stereoselectivity issues. Herein we demonstrate a general, chemoselective and direct synthesis of (Z)-2-butene-1,4-diol monoesters. The protocol operates within a Pd-catalyzed decarboxylative acyloxylation regime involving vinyl ethylene carbonates (VECs) and various carboxylic acids as the reaction partners under mild and operationally attractive conditions. The newly developed process allows access to a structurally diverse pool of (Z)-2-butene-1,4-diol monoesters in good yields and with excellent regio- and stereoselectivity. Various synthetic transformations of the obtained (Z)-2-butene-1,4-diol monoesters demonstrate how these synthons are of great use to rapidly diversify the portfolio of these formal desymmetrized (Z)-alkenes.

Base-Mediated Defluorosilylation of C(sp2 )-F and C(sp3 )-F Bonds.

The ability to selectively forge C-heteroatom bonds by C-F scission is typically accomplished by metal catalysts, specialized ligands and/or harsh reaction conditions. Described herein is a base-mediated defluorosilylation of unactivated C(sp2 )-F and C(sp3 )-F bonds that obviates the need for metal catalysts. This protocol is characterized by its simplicity, mild reaction conditions, and wide scope, even within the context of late-stage functionalization, constituting a complementary approach to existing C-Si bond-forming protocols.

Ni-Catalyzed Borylation of Aryl Fluorides via C-F Cleavage.

A Ni-catalyzed borylation via C-F activation is described. This protocol is distinguished by a wide scope, including unactivated fluoroarenes, without compromising its efficiency and scalability, thus representing a significant step-forward toward the implementation of C-F activation protocols.

Impact of chronic low to moderate alcohol consumption on blood lipid and heart energy profile in acetaldehyde dehydrogenase 2-deficient mice.

AIM: To investigate the roles of acetaldehyde dehydrogenase 2 (ALDH2), the key enzyme of ethanol metabolism, in chronic low to moderate alcohol consumption-induced heart protective effects in mice. METHODS: Twenty-one male wild-type (WT) or ALDH2-knockout (KO) mice were used in this study. In each genotype, 14 animals received alcohol (2.5%, 5% and 10% in week 1-3, respectively, and 18% in week 4-7), and 7 received water for 7 weeks. After the treatments, survival rate and general characteristics of the animals were evaluated. Serum ethanol and acetaldehyde levels and blood lipids were measured. Metabolomics was used to characterize the heart and serum metabolism profiles. RESULTS: Chronic alcohol intake decreased the survival rate of KO mice by 50%, and significantly decreased their body weight, but did not affect those of WT mice. Chronic alcohol intake significantly increased the serum ethanol levels in both WT and KO mice, but KO mice had significantly higher serum acetaldehyde levels than WT mice. Chronic alcohol intake significantly increased the serum HDL cholesterol levels in WT mice, and did not change the serum HDL cholesterol levels in KO mice. After chronic alcohol intake, WT and KO mice showed differential heart and serum metabolism profiles, including the 3 main energy substrate types (lipids, glucose and amino acids) and three carboxylic acid cycles. CONCLUSION: Low to moderate alcohol consumption increases HDL cholesterol levels and improves heart energy metabolism profile in WT mice but not in ALDH2-KO mice. Thus, preserved ALDH2 function is essential for the protective effect of low to moderate alcohol on the cardiovascular system.

Palladium-catalyzed C(sp(3))-H activation: a facile method for the synthesis of 3,4-dihydroquinolinone derivatives.

3,4-Dihydroquinolinones were synthesized by the palladium-catalyzed, oxidative-addition-initiated activation and arylation of inert C(sp(3) )H bonds. Pd(OAc)2 and P(o-tol)3 were used as the catalyst and ligand, respectively, to improve the efficiency of the reaction. A further advantage of this reaction is that it could be performed in air. A relatively rare seven-membered palladacycle was proposed as a key intermediate of the catalytic cycle.

An organocatalyst bearing stereogenic carbon and sulfur centers as an efficient promoter for enantioselective hydrosilylation of 1,4-benzooxazines.

The efficient and enantioselective hydrosilylation of 3-aryl-1,4-benzooxazines was achieved using an l-phenyl alanine derived new Lewis base catalyst bearing stereogenic carbon and sulfur centers. In the presence of 2 mol % of catalyst, a broad range of 3-aryl-1,4-benzooxazines were hydrosilylated to afford the corresponding chiral 3-aryl-3,4-dihydro-2H-1,4-benzooxazine products with good to high yields (66-98%) and enantioselectivities (70-99% ee). This method provides an alternative approach with great practical application potential to access chiral 3-aryl-3,4-dihydro-2H-1,4-benzooxazines.

Study on the Relationship Between PTPRO Methylation in Plasma and Efficacy Neoadjuvant Chemotherapy in Patients with Early Breast Cancer.

Objective: This study aimed to explore the correlation between PTPRO methylation in plasma and the efficacy of neoadjuvant chemotherapy (NAC) for early breast cancer (BC). Methods: Eighty-two patients with early BC undergoing NAC were included. PTPRO methylation status in plasma before and after NAC was detected using methylation-specific PCR and the relationship between PTPRO methylation and NAC efficacy was analyzed. Results: The rate of pathologic complete response (pCR) was only 25.0% (12/48) in patients with positive PTPRO methylation result before NAC, but 61 0.8% (21/34) in pre-NAC methylation-negative patients (OR = 0.24, 95% CI: 0.09-0.65, P = 0.005). In addition, the pCR rate was 12.1% (4/33) in patients with positive PTPRO methylation results both before and after NAC, but 53.3% (8/15) in patients with pre-NAC positive methylation and post-NAC negative methylation results (OR = 0.12, 95% CI: 0.03-0.52, P = 0.004). Conclusion: Plasma PTPRO methylation is a potential biomarker for predicting the efficacy of NAC in early BC.

Highly enantioselective reduction of ß-amino nitroolefins with a simple N-sulfinyl urea as bifunctional catalyst.

Simple but effective: A structurally simple N-sulfinyl urea was found to be a highly efficient bifunctional catalyst, which allows for the development of a novel pathway for the construction of chiral ß-amino nitroalkanes through enantioselective reduction of ß-amino nitroolefins by trichlorosilane. High yields and excellent enantioselectivities were obtained for a broad range of ß-arylamino nitroolefin substrates (see scheme).

Diversified syntheses of multifunctionalized thiazole derivatives via regioselective and programmed C-H activation.

The sequential construction of diversified multifunctionalized thiazole derivatives through Pd-catalyzed regioselective C-H alkenylation has been accomplished. This versatile approach provides the diversified thiazole derivatives featuring orthogonal substitution patterns at the C-2, C-4 and C-5 positions from mono-substituted (2- or 4-substituted) thiazole derivatives or even more challenging simple thiazole.

Reigoselective arylation of thiazole derivatives at 5-position via Pd catalysis under ligand-free conditions.

An efficient regioselective arylation of thiazole derivatives via Pd-catalyzed C-H activation is reported. The transformation was hypothesized through a Pd(0/II) catalytic cycle in the absence of special ligand sets. This method provided an efficient process to direct arylation of thiazoles at the 5-position.