Phosphine-Catalyzed Domino Annulation of γ-Vinyl Allenoates: Synthesis of Tetrahydrofuro[3,2-]quinoline Derivatives.

A novel phosphine-catalyzed domino annulation reaction of γ-vinyl allenoates and -aminotrifluoacetophenones for the construction of terahydrofuro[3,2-]quinoline derivatives has been developed. In this domino reaction, two kinds of terahydrofuro[3,2-]quinoline compounds containing CF groups were obtained with good yields under mild conditions, three new C-N, C-C, and C-O bonds can be built in one step, and the reaction selectivity is achieved by adjusting the reaction conditions. Furthermore, preliminary studies on an asymmetric variant of this reaction proceeded with moderate enantioselectivity.

Rnd3 suppresses endothelial cell pyroptosis in atherosclerosis through regulation of ubiquitination of TRAF6.

Background: As the main pathological basis for various cardiovascular and cerebrovascular diseases, atherosclerosis has become one of the leading causes of death and disability worldwide. Emerging evidence has suggested that Rho GTPase Rnd3 plays an indisputable role in cardiovascular diseases, although its function in atherosclerosis remains unclear. Here, we found a significant correlation between Rnd3 and pyroptosis of aortic endothelial cells (ECs).

Cardiac Metabolism, Reprogramming, and Diseases.

Cardiovascular diseases (CVD) account for the largest bulk of deaths worldwide, posing a massive burden on societies and the global healthcare system. Besides, the incidence and prevalence of these diseases are on the rise, demanding imminent action to revert this trend. Cardiovascular pathogenesis harbors a variety of molecular and cellular mechanisms among which dysregulated metabolism is of significant importance and may even proceed other mechanisms.

Photoinduced Three-Component Difluoroalkylation of Quinoxalinones with Alkenes via Difluoroiodane(III) Reagents.

An environmentally friendly strategy for the photocatalyzed three-component reaction between quinoxalinones, alkenes, and hypervalent iodine(III) reagents is disclosed. The new designed difluoroiodane(III) reagent shows excellent reactivity, providing a wide range of difluoroalkyl-substituted quinoxaline-2(1)-ones in moderate to excellent yields under mild conditions. Experimental studies demonstrated that a difluoroalkyl radical intermediate was involved in this reaction.

Phosphine-Catalyzed (3 + 2)/(3 + 2) Sequential Annulation of γ-Vinyl Allenoates: Access to Fused Carbocycles.

The first (3 + 2)/(3 + 2) sequential annulation of γ-vinyl allenoates with alkylidenemalononitriles enabled by phosphine catalysis has been reported. A broad range of structurally dense tetra- and penta-substituted bicyclic[3,3,0]octene derivatives, containing a quaternary center and three sequential stereogenic center, were synthesized in good to excellent yields. In this approach, three new C-C bonds are formed in one pot, and εC and αC of γ-vinyl allenoate are two electrophilic centers, whereas its γC exhibits nucleophilic reactivity.

Phosphine-catalyzed (3+2)/(2+3) sequential annulation involving a triple nucleophilic addition reaction of γ-vinyl allenoates.

A phosphine-catalyzed (3+2)/(2+3) sequential annulation involving a triple nucleophilic addition reaction of γ-vinyl allenoates was successfully developed. The reaction provided efficient and more practical access to functionalized hydropyrroloimidazolones with good to excellent yields under mild reaction conditions. Notably, γ-vinyl allenoate served as a triple-electrophilic intermediate in this protocol.

Sequential Phosphine-Catalyzed [4 + 2] Annulation of β'-Acetoxy Allenoates: Enantioselective Synthesis of 3-Ethynyl-Substituted Tetrahydroquinolines.

The first enantioselective sequential phosphine-catalyzed (SPC as abbreviation) mode for the formation of tetrahydroquinolines with an ethynyl-substituted all-carbon quaternary stereogenic center is reported. In this SPC process, a novel [4 + 2] annulation process was devised employing α-substituted allenoates as C2 synthons (α-β', 1,2-dipole) for the first time. 3-Ethynyl-substituted tetrahydroquinolines were readily prepared in good yields and high enantioselectivities.

Mst1 inhibits CMECs autophagy and participates in the development of diabetic coronary microvascular dysfunction.

Cardiovascular complications account for a substantial proportion of morbidity and mortality in diabetic patients. Abnormalities of cardiac microvascular endothelial cells (CMECs) lead to impaired cardiac microvascular vessel integrity and subsequent cardiac dysfunction, underlining the importance of coronary microvascular dysfunction. In this study, experimental diabetes models were constructed using Mst1 transgenic, Mst1 knockout and sirt1 knockout mice.

MST1 coordinately regulates autophagy and apoptosis in diabetic cardiomyopathy in mice.

Aims/hypothesis: Diabetic cardiomyopathy (DCM) is associated with suppressed autophagy and augmented apoptosis in the heart although the interplay between the two remains elusive. The ability of mammalian sterile 20-like kinase 1 to regulate both autophagy and apoptosis prompted us to investigate it as a possible candidate in the progression of DCM.

Methods: Wild-type, Mst1 (also known as Stk4) transgenic and Mst1-knockout mice were challenged with streptozotocin to induce experimental diabetes.