Gold-Catalyzed Cascade Reaction of Yne-Enones with Iminooxindoles, Access to 3,2'-Pyrrolidinyl-Spirooxindole Derivatives.

Herein, a gold-catalyzed cascade reaction of yne-enones with iminooxindoles has been developed through a cascade cycloisomerization/(3 + 2) annulation process. This approach provides a straightforward and efficient route for the synthesis of functionalized 3,2'-pyrrolidinyl-spirooxindoles in high reactivity and broad substrate scope with excellent cis-selectivity. Moreover, the subsequent functionalization of furan units allows for the diverse synthesis of spirooxindole derivatives, which have demonstrated good antitumoral activity.

SPHENOL, A New Chiral Framework for Asymmetric Synthesis.

Privileged chiral catalysts have found tremendous applications and thus immensely advanced asymmetric synthesis in the past few decades. However, truly privileged chiral frameworks are still extremely limited. Thus, the search for and development of new versatile members remain in high demand but challenging. Herein we report the design, synthesis, and application of a new chiral framework, SPHENOL, which features combined advantages of BINOL and SPINOL. This unique feature enables SPHENOL to serve as a new platform for the development of chiral ligands and catalysts. Its superior performance has been demonstrated in mechanistically unrelated reactions, including asymmetric hydrogenation, hydroacylation, and spirocyclization for the practical asymmetric synthesis of SPHENOL itself. These results indicated the great potential of SPHENOL as a useful chiral framework.

Moderate exercise ameliorates osteoarthritis by reducing lipopolysaccharides from gut microbiota in mice.

Lipopolysaccharides (LPSs) released by gut microbiota are correlated with the pathophysiology of osteoarthritis (OA). Exercise remodels the composition of gut microbiota. The present study investigated the hypothesis that wheel-running exercise prevents knee OA induced by high-fat diet (HFD) via reducing LPS from intestinal microorganisms. Male C57BL/6 J mice were treated with sedentary or wheel-running exercise, standard diet (13.5% kcal) or HFD (60% kcal), berberine or not according to their grouping. Knee OA severity, blood and synovial fluid LPS, cecal microbiota, and TLR4 and MMP-13 expression levels were determined. Our findings reveal that HFD treatment decreased gut microbial diversity. Increase in endotoxin-producing bacteria, decrease in gut barrier-protecting bacteria, high LPS levels in the blood and synovial fluid, high TLR4 and MMP-13 expression levels, and severe cartilage degeneration were observed. By contrast, voluntary wheel running caused high gut microbial diversity. The gut microbiota were reshaped, LPS levels in the blood and synovial fluid and TLR4 and MMP-13 expression levels were low, and cartilage degeneration was ameliorated. Berberine treatment reduced LPS levels in the samples, but decreased the diversity of intestinal flora with similar changes to that caused by HFD. In conclusion, unlike taking drugs, exercising can remodel gut microbial ecosystems, reduce the circulating levels of LPS, and thereby contribute to the relief of chronic inflammation and OA. Our findings showed that moderate exercise is a potential therapeutic approach for preventing and treating obesity-related OA.

Asymmetric Synthesis of Axially Chiral Anilides via Organocatalytic Atroposelective N-Acylation.

A highly atroposelective N-acylation reaction of aniline-derived sulfonamides has been developed with chiral isothiourea as the catalyst. This approach provides a facile and efficient route to an array of atropoisomeric sulfonyl substituted anilide products in good yields with high to excellent enantioselectivities.

Bimetallic Catalytic Tandem Reaction of Acyclic Enynones: Enantioselective Access to Tetrahydrobenzofuran Derivatives.

A highly efficient enantioselective synthesis of multisubstituted tetrahydrobenzofuran derivatives with four contiguous stereocenters was established by the dual catalysis of a gold(I)/chiral N,N'-dioxide-cobalt(II) complex via a tandem cycloisomerization/Diels-Alder reaction of 2-alkynyl-2-alkenones and electron-deficient olefins. This strategy was not only featured with atom economy, remarkable efficiency and stereoselectivity but also was highlighted by further transformations of the furan-based products into polycyclic molecules. Moreover, a possible transition-state model was proposed to elucidate the origin of stereoselectivity.

Enantioselective Vinylogous Michael-Aldol Reaction To Synthesize Spirocyclohexene Pyrazolones in Aqueous Media.

An efficient asymmetric vinylogous Michael-aldol domino reaction between α-arylidene pyrazolinones and ß,γ-unsaturated-α-ketoesters catalyzed by a chiral N, N'-dioxide-ScIII complex in aqueous media has been established. A variety of spirocyclohexene pyrazolones with three stereocenters including vicinal tetrasubstituted stereocenters were obtained in excellent yields with good diastereoselectivities and enantioselectivities. A retro-aldol process was observed, which led to epimerization at the spirocyclic quaternary carbon center.

Bimetallic Catalytic Asymmetric Tandem Reaction of ß-Alkynyl Ketones to Synthesize 6,6-Spiroketals.

The enantioselective tandem reaction of ß,γ-unsaturated α-ketoesters with ß-alkynyl ketones was realized by a bimetallic catalytic system of achiral AuΙΙΙ salt and chiral N,N'-dioxide-MgΙΙ complex. The cycloisomerization of ß-alkynyl ketone and asymmetric intermolecular [4+2] cycloaddition with ß,γ-unsaturated α-ketoesters subsequently occurred, providing an efficient and straightforward access to chiral multifunctional 6,6-spiroketals in up to 97 % yield, 94 % ee and >19/1 d.r. Besides, a catalytic cycle was proposed based on the results of control experiments.

Catalytic enantioselective ene-type reactions of vinylogous hydrazone: construction of α-methylene-γ-butyrolactone derivatives.

The catalytic asymmetric ene-type reactions of vinylogous hydrazone were accomplished by using chiral N,N'-dioxide-metal salt complexes as catalysts. A wide range of electrophiles, including isatins, α-ketoester, imines, and aldehydes reacted with (E)-2-methyl-N-(piperidin-1-yl)prop-2-en-1-imine efficiently, affording the corresponding homoallylic alcohols and amines in high yields (up to 99%) with excellent ee values (up to 99%). The methodology provided a convenient way to synthesize bioactive chiral α-methylene-γ-butyrolactone derivatives.

Chiral N,N'-dioxide/Sc(OTf)3 complex-catalyzed asymmetric dearomatization of ß-naphthols.

An efficient N,N'-dioxide-scandium(iii) complex catalytic system has been developed for the asymmetric dearomatization of ß-naphthols through conjugate addition to alkynones. A variety of Z-predominated ß-naphthalenone compounds were obtained in moderate to high yields with excellent enantioselectivities (up to 98% ee). Moreover, a possible transition state was proposed to explain the origin of the stereoselectivity.

A Chiral N,N'-Dioxide-Zn(II) Complex Catalyzes the Enantioselective [2+2] Cycloaddition of Alkynones with Cyclic Enol Silyl Ethers.

A highly efficient enantioselective [2+2] cycloaddition between alkynones and cyclic enol silyl ethers was developed by using a chiral N,N'-dioxide-zinc(II) complex as a catalyst. This method functions well for a variety of terminal alkynes as well as cyclic enol silyl ethers, with good to excellent enantioselectivity (up to 97 % ee). This is also the first successful example for the catalytic enantioselective [2+2] cycloaddition of internal alkynes with cyclic enol silyl ethers to give fully substituted cyclobutenes. Meanwhile, the desired cyclobutene product can easily be transformed into fused cyclobutane derivatives.