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Objective The aim of this study was to determine the therapeutic effect of piperlongumine on hypoxic pulmonary hypertension. Methods A hypoxic pulmonary hypertension rat model was constructed, primary rat pulmonary artery smooth muscle cells (PASMCs) were isolated, and the proliferation of PASMCs was measured by Cell Counting Kit‑8 assay. The expression of autophagic proteins microtubule-associated protein 1 light chain 3B (LC3B) and P62 were examined by western blot. Autophagic flux in PASMCs was detected by tandem mRFP-GFP-LC3 fluorescence analysis. Results Hypoxia-induced proliferation of PASMCs was significantly inhibited by piperlongumine exposure. Treatment with piperlongumine elevated LC3B II/LC3B I protein ratio and decreased the expression of P62 protein in both PASMCs and rat lung tissues. Tandem mRFP-GFP-LC3 fluorescence analysis showed that piperlongumine increased autophagic flux in PASMCs. Inhibition of autophagy using 3-methyladenine (3-MA) attenuated the inhibitory effect of piperlongumine on proliferation of PASMCs. Chronic hypoxia exposure led to a significant increase in rat right ventricle systolic pressure, right ventricular hypertrophy, wall thickness and area of pulmonary artery, and muscularization of pulmonary arterioles, which was obviously suppressed by administration of piperlongumine. 3-MA attenuated the alleviating effects of piperlongumine on pulmonary vascular remodeling. Conclusions Piperlongumine attenuates vascular remodeling in hypoxic pulmonary hypertension by regulating autophagy. Piperlongumine treatment may serve as a promising therapy for hypoxic pulmonary hypertension.

Direct functionalization of inert C(sp3)–H bonds is a topic of immense contemporary interest and exceptional value in organic synthesis. The recent research has established a novel and practical protocol which features the engagement of vinyl cation species to functionalize C(sp3)–H bonds. The discussion of the topic is arranged by the strategies to generate the reactive intermediates, including ionization of vinyl triflates, addition of electrophiles to alkynes, tandem cyclization of enynes or diynes, and decomposition of β -hydroxy- α -diazo ketones. This review closes with a personal perspective on the dynamic research area of unactivated C(sp3)–H functionalization via vinyl cations. Hopefully, it will provide timely illumination and beneficial guidance for organic chemists who are interested in this area, meanwhile, continued development of the field is strongly anticipated in the future.

An efficient copper-catalyzed cyclization of N-propargyl ynamides with borane adducts through B-H bond insertion has been developed. A series of valuable organoboron compounds are constructed in generally good yields with a wide substrate scope and good functional group tolerance under mild reaction conditions. Importantly, this protocol via vinyl cation intermediates constitutes a novel way of B-H bond insertion.

Transition-metal-catalyzed intramolecular carboalkoxylation of alkynes has attracted much attention in the past decades due to its high bond-forming efficiency and atom economy in the rapid assembl...

Transition-metal-catalyzed alkyne hydration reaction has attracted considerable interest in the past decades because this approach would lead to the facile and efficient formation of synthetically ...

During the past two decades, gold-catalyzed nitrene-transfer reactions via α-imino gold carbenes have received extensive attention, as this strategy provides rapid access to nitrogen-containing molecules with high efficiency. In this review, we focus on recent progress in gold-catalyzed formal annulations of ynamides with isoxazole derivatives as nitrene-transfer reagents via α-imino gold carbenes in atom-economic and rapid construction of N-heterocycles.

Metal carbenes have proven to be one of the most important and useful intermediates in organic synthesis, but catalytic asymmetric reactions involving metal carbenes are still scarce and remain a challenge. Particularly, the mechanistic pathway and chiral induction model in these asymmetric transformations are far from clear. Described herein is a copper-catalyzed asymmetric cyclization of alkenyl diynes involving a vinylic C(sp2)–H functionalization, which constitutes the first asymmetric vinylic C(sp2)–H functionalization through cyclopentannulation. Significantly, based on extensive mechanistic studies including control experiments and theoretical calculations, a revised mechanism involving a novel type of endocyclic copper carbene via remote-stereocontrol is proposed, thus providing new mechanistic insight into the copper-catalyzed asymmetric diyne cyclization and representing a new chiral control pattern in asymmetric catalysis based on remote-stereocontrol and vinyl cations. This method enables the practical and atom-economical construction of an array of valuable chiral polycyclic-pyrroles in high yields and enantioselectivities., A copper-catalyzed asymmetric cyclization of alkenyl diynes involving a vinylic C(sp2)–H functionalization is reported, enabling the construction of various valuable chiral polycyclic-pyrroles in high yields and enantioselectivities.

ConspectusYnamides are electron-rich heteroatom-substituted alkynes with a C-C triple bond directly attached to the amide group. Importantly, this amide group is able to impose an electronic bias, thus resulting in the highly regioselective attack of this polarized alkyne by a large variety of nucleophiles. Over the past two decades, catalytic reactions of ynamides have experienced dramatic developments, especially those catalyzed by transition metals. As a result, ynamides have been widely applied to the rapid and efficient assembly of versatile structurally complex N-containing molecules, especially in an atom-economic and stereoselective way.On the basis of newly developed ynamide preparations and new alkyne transformations, we first developed oxidation-initiated tandem reactions of ynamides such as zinc-catalyzed ynamide oxidation/C-H functionalization and copper-catalyzed ynamide oxidation/carbene metathesis, leading to divergent synthesis of isoquinolones, β-carbolines, and pyrrolo[3,4

Catalytic transformations involving metal carbenes are considered one of the most important aspects of homogeneous transition metal catalysis. Recently, gold-catalyzed generation of gold carbenes from readily available alkynes represents a significant advance in metal carbene chemistry. This Review summarizes the advances in the gold-catalyzed nitrene-transfer reactions of alkynes with nitrogen-transfer reagents, such as azides, nitrogen ylides, isoxazoles, and anthranils, and gold-catalyzed carbene-transfer reactions, involving oxygen atom-transfer reactions of alkynes with nitro compounds, nitrones, sulfoxides, and pyridine N-oxides, through the presumable α-imino gold carbene and α-oxo gold carbene intermediates, respectively. Gold-catalyzed processes are reviewed by highlighting their product diversity, selectivity, and applicability, and the mechanistic rationale is presented where possible.

Objective: To determine the combined efficacy of piperlongumine and gemcitabine for treatment of KRAS mutant lung cancer. Methods: The cell growth inhibition of piperlongumine, gemcitabine, and piperlongumine plus gemcitabine was measured by Cell Counting Kit‑8 assay and the combination index was calculated. In addition, the combined effects of piperlongumine and gemcitabine on cell apoptosis, reactive oxygen species (ROS) contents, and microtubule-associated protein 1 light chain 3B (LC3B) expression were examined. Results: Piperlongumine increased ROS contents and LC3B-II expression. Following the combined treatment with piperlongumine and 10 mM N-acetyl-L-cysteine (NAC), intracellular ROS and cell viability returned to normal levels, and the expression of LC3B-II decreased to the predose level. Gemcitabine also induced cell apoptosis, increased ROS contents, and LC3B-II expression. The combination of piperlongumine with gemcitabine exhibited a synergetic anticancer activity with the combination index Conclusion: Combination therapy with piperlongumine and gemcitabine is a promising treatment option for KRAS mutant lung cancer.

An efficient gold-catalyzed anti-Markovnikov cycloisomerization-initiated tandem reaction of Boc-protected indole tethered homopropargyl amides has been achieved. This method delivers a wide range of valuable bridged aza-[n.2.1] skeletons (n = 3–7) at room temperature with high diastereoselectivity and enantioselectivity by a chirality-transfer strategy. Moreover, the gold-catalyzed tandem reaction of homopropargyl alcohol is also achieved to produce the bridged oxa-[3.2.1] skeleton.

Over the past two decades, the development and application of ynamide chemistry have received more and more attention. Ynamides have proven to be versatile reagents for organic synthesis, and have been widely applied to the rapid assembly of a diverse range of structurally complex N-containing molecules, especially the valuable N-heterocycles. In comparison with the well-established transition metal-catalyzed reactions of ynamides, metal-free ynamide transformations have relatively seldom been exploited. Recently, Brønsted acid-mediated reactions of ynamides represent significant advances in ynamide chemistry. This review summarizes the latest trends and developments of Brønsted acid-mediated reactions of ynamides, including cycloaddition, cyclization, intramolecular alkoxylation-initiated rearrangement, oxygen atom transfer reactions and hydro-heteroatom addition reactions.

An efficient visible-light-mediated ketyl–ynamide coupling by employing ynamides bearing alkyl sulfonyl substituents to deliver eneindolin-3-ols has been developed. Subsequent 1,3-transposition of allylic alcohols in one pot is capable of synthesizing 2-hydroxymethylindoles in generally moderate to good yields. The synthetic utility of this protocol has also been demonstrated by the facile and practical synthesis of two bioactive molecules. The use of readily available substrates, a simple procedure and benign reaction conditions render this method a viable alternative for the synthesis of 2-hydroxymethylindoles.

This article gives a short review on the visible-light promoted synthesis of α-functionalized ketones from alkenes. Various α-functionalized ketones, including α-halo, sulfinyl/sulfonyl, aryl, azido and thiocyanato ketones can be synthesized from the reaction of alkenes with different radical species generated by visible-light catalysis. These transformations typically use dioxygen as the terminal oxidant and do not require a transition metal to activate the double bond, which is quite different from the transition-metal catalysed reactions (Wacker oxidation or hydroformylation).

An efficient copper-catalyzed tandem regioselective cis-carbometallation/cyclization of imine-ynamides with arylboronic acids has been developed. This method leads to a facile and practical synthesis of valuable 2,3-disubstituted indolines in moderate to excellent yields and features a broad substrate scope and wide functional group tolerance. Other significant features of this protocol include the use of readily available starting materials, high flexibility, simple procedure and mild reaction conditions.

A palladium catalysed Ullmann biaryl synthesis has been developed using hydrazine hydrate as the reducing reagent at room temperature. The combination of Pd(OAc)2 and hydrazine hydrate works smoothly for the coupling of both electron-rich and electron-deficient aryl iodides, as well as hetero-aryl iodides, leading to a wide range of biaryls in good to excellent yields. The reaction requires only 1 mol% Pd(OAc)2 and the in situ generated palladium naoparticles are found to be active catalysts.

An efficient regio- and diastereoselective method for the construction of valuable trans-3,4-diaryldihydrocoumarins via metal-free [4+2] annulation of ynamides with o-hydroxybenzyl alcohols has been developed. Ynamides are first treated as 2-π partners to react with o-hydroxybenzyl alcohols via traceless sulfonamide directing groups, affording trans-3,4-diaryldihydrocoumarins in good yields with high regio- and diastereoselectivities. This metal-free methodology is also characterized by a wide substrate scope, good functional group tolerance, and efficiency on a gram scale.

Here an efficient copper-catalyzed cascade cyclization of azide-ynamides via α-imino copper carbene intermediates is reported, representing the first generation of α-imino copper carbenes from alkynes. This protocol enables the practical and divergent synthesis of an array of polycyclic N-heterocycles in generally good to excellent yields with broad substrate scope and excellent diastereoselectivities. Moreover, an asymmetric azide-ynamide cyclization has been achieved with high enantioselectivities (up to 98:2 e.r.) by employing BOX-Cu complexes as chiral catalysts. Thus, this protocol constitutes the first example of an asymmetric azide-alkyne cyclization. The proposed mechanistic rationale for this cascade cyclization is further supported by theoretical calculations.

The generation of metal-containing 1,3-dipoles from metal carbenes represents a significant advance in 1,3-dipolar cycloaddition reactions. However, these transformations have so far been limited to reactions based on diazo compounds or triazoles as precursors. Herein, we disclose a copper-catalyzed enantioselective reaction of alkenyl N-propargyl ynamides with styrene derivatives by formal [3 + 2] cycloaddition via Cu-containing all-carbon 1,3-dipoles, which constitutes a novel way for the generation of metal-containing 1,3-dipoles via metal carbenes. This protocol allows the practical and atom-economical synthesis of valuable chiral pyrrole-fused bridged [2.2.1] skeletons in moderate to good yields (up to 90% yield) with excellent diastereoselectivities (dr > 50/1) and generally excellent enantioselectivities (up to >99% ee).

In the past decades, significant advances have been made on radical Smiles rearrangement. However, the eventually formed radical intermediates in these reactions are limited to the amidyl radical, except for the few examples initiated by a N-centered radical. Here, a novel and practical radical Smiles rearrangement triggered by photoredox-catalyzed regioselective ketyl-ynamide coupling is reported, which represents the first radical Smiles rearrangement of ynamides. This method enables facile access to a variety of valuable 2-benzhydrylindoles with broad substrate scope in generally good yields under mild reaction conditions. In addition, this chemistry can also be extended to the divergent synthesis of versatile 3-benzhydrylisoquinolines through a similar ketyl-ynamide coupling and radical Smiles rearrangement, followed by dehydrogenative oxidation. Moreover, such an ynamide Smiles rearrangement initiated by intermolecular photoredox catalysis via addition of external radical sources is also achieved. By control experiments, the reaction was shown to proceed via key ketyl radical and α-imino carbon radical intermediates.

This chapter focuses on transition metal-catalyzed reactions using isoxazoles, anthranils and 1,2-benzisoxazoles. Selected topics include the use of these nitroxy aromatic species in (i) metal-catalyzed annulations of alkynes (ii) catalytic reactions with metal carbenes and (iii) catalytic aminations of aryl C H bonds. In the alkyne annulation, these aromatic species typically generate α-imino gold carbenes that can further be elaborated to form various azacyclic compounds via a suitable functionality on alkynes, whereas with metal carbenes prototypical reactivity involves their imination. For Rh(I)-catalyzed aryl C H aminations, these N O aromatic species react with Rh metalocycles to cleave their N O bond and form a Rh N bond, furnishing Ar N bond formation. The large family of azacyclic products accessible from these three reactions further highlight their synthetic utility.

Carbene cascade reactions involving carbene/alkyne metathesis have attracted much attention over the past decades because this chemistry offers great potential to build complicated cyclic molecules. However, the formed vinyl metal carbenoids in these reactions are limited to exocyclic carbenes, and the generation of endocyclic vinyl carbene complexes remains unexplored. Here, we report an unprecedented gold-catalyzed oxidative cyclization of terminal diynes. Importantly, the generation of endocyclic vinyl carbene complexes was involved in this oxidative cyclization, which is distinctively different from previous protocols. This method allows the facile synthesis of various valuable naphthoquinones and carbazolequinones from readily available diynes under exceptionally mild reaction conditions and features a broad substrate scope and wide functional group tolerance. Moreover, theoretical calculations provide further evidence on the divergent selectivity of this cyclization reaction.

Herein, we disclose an efficient zinc-catalyzed formal [3 + 2] annulation of isoxazoles with ynol ethers under exceptionally mild reaction conditions, leading to the atom-economical and divergent synthesis of 2-alkoxyl 1H-pyrroles and 3H-pyrroles, respectively. Importantly, this zinc-catalyzed protocol demonstrates the dramatically divergent reactivity from the relevant platinum catalysis, where the formal [4 + 2] annulation of isoxazoles with ynol ethers was involved. In addition, theoretical calculations provide further evidence for the feasibility of the proposed reaction mechanism, especially the distinct selectivity.

The highly efficient and selective construction of carbon–carbon bond in an atom-economic and mild way is still one of the cores of modern organic synthesis. The strategy of Claisen rearrangement triggered by catalytic alkyne alkoxylation shows the unique advantage in the carbon–carbon bond formation and has attracted widespread attention during the past two decades. The intramolecular protocol is usually regarded as a powerful tool for the synthesis of functionalized heterocycles, which are widely distributed in natural products and bioactive molecules. Meanwhile, the catalytic intermolecular tandem cyclization/Claisen rearrangement also provides a facile and practical approach for the rapid construction of complicated compounds, which contain valuable core skeletons of various targeted molecules. Recent advances in this rapidly expanding field involving transition metal-catalyzed tandem alkyne alkoxylation/Claisen rearrangement were introduced in this minireview. These related articles were organized via different catalytic species: single-metal catalysis and bimetallic catalysis. A discussion of the reaction scope, mechanistic insights, and synthetic applications of this tandem process is presented.

Ynamides are important building blocks in organic synthesis, and a variety of versatile synthetic methods have been developed in the past decade. Among these, catalytic cyclizations of π-tethered ynamides are particularly attractive, since this approach enables facile access to a diverse array of synthetically useful nitrogen heterocycles. However, due to the fact that the nitrogen atom is able to impose an electronic bias, these cyclizations exclusively occur on the α position of ynamides. Herein, we report the reversal of regioselectivity in arene-ynamide cyclization by copper catalysis, which represents the first catalytic π-tethered ynamide cyclization involving the reversal of regioselectivity. This strategy allows the expedient and practical synthesis of valuable azepino[4,5-b]indoles and β-carbolines in generally high yields under mild conditions. Moreover, the relevant mechanistic rationale for this cyclization, especially for the observed high regioselectivity, is strongly supported by density fu...

6π electrocyclization has attracted interest in organic synthesis because of its high stereospecificity and atom economy in the construction of versatile 5-7-membered cycles. However, examples of asymmetric 6π electrocyclization are quite scarce, and have to rely on the use of chiral organocatalysts, and been limited to pentadienyl-anion- and triene-type 6π electrocyclizations. Described herein is a zinc-catalyzed formal [4+3] annulation of isoxazoles with 3-en-1-ynol ethers via 6π electrocyclization, leading to the site-selective synthesis of functionalized 2H-azepines and 4H-azepines in good to excellent yields with broad substrate scope. Moreover, this strategy has also been used to produce chiral 2H-azepines with high enantioselectivities (up to 97:3 e.r.). This protocol not only is the first asymmetric heptatrienyl-cation-type 6π electrocyclization, but also is the first asymmetric reaction of isoxazoles with alkynes and the first asymmetric catalysis based on ynol ethers.

The generation of metal carbenes from readily available alkynes represents a significant advance in metal carbene chemistry. However, most of these transformations are based on the use of noble-metal catalysts and successful examples of such an asymmetric version are still very scarce. Here a copper-catalyzed enantioselective cascade cyclization of N-propargyl ynamides is reported, enabling the practical and atom-economical construction of diverse chiral polycyclic pyrroles in generally good to excellent yields with wide substrate scope and excellent enantioselectivities (up to 97:3 e.r.). Importantly, this protocol represents the first copper-catalyzed asymmetric diyne cyclization. Moreover, mechanistic studies revealed that the generation of donor/donor copper carbenes is presumably involved in this 1,5-diyne cyclization, which is distinctively different from the related gold catalysis, and thus it constitutes a novel way for the generation of donor/donor metal carbenes.

Reversion mutations are associated with clinical resistance to poly(ADP-ribose) polymerase inhibitors (PARPi). Here, we describe the detection of a BRCA1 reversion mutation in a 39-year-old woman with metastatic breast cancer harboring a heterozygous germline BRCA1 exons 7–8 deletion who received PARPi olaparib combined with immune checkpoint inhibitor camrelizumab as third-line therapy. During progression from the olaparib and camrelizumab combination therapy, we identified via genomic sequencing a novel 7-base pair somatic deletion in BRCA1 (c.617_623delACAAATC). Sequence analyses indicated that this mutation realigned the reading frame of BRCA1, which potentially led to the reversal of its normal function and conferred resistance to PARPi.

In a dual visible light photoredox and gold catalysis system, Au(I) is oxidized in a stepwise fashion by photogenerated aryl radicals leading to cationic Au(III) species, a process which is incorporated into various domino functionalization/coupling reactions. This article presents an overview of the major contributions reported in this field, emphasizing those involving aryldiazonium or diaryliodonium salts as general radical sources. 1 Introduction 2 Domino Nucleophilic Addition/Arylation 3 Domino Rearrangement/Arylation 4 Cross-Coupling 5 Conclusion

Platinum-catalyzed formal [5+2] and [4+2] annulations of isoxazoles with heterosubstituted alkynes enabled the atom-economical synthesis of valuable 1,3-oxazepines and 2,5-dihydropyridines, respectively. Importantly, this Pt catalysis not only led to unique reactivity dramatically divergent from that observed under Au catalysis, but also proceeded via unprecedented α-imino platinum carbene intermediates.

A novel gold-catalyzed tandem cycloisomerization/hydrogenation of chiral homopropargyl sulfonamides has been developed. Various enantioenriched pyrrolidines can be obtained in excellent yields and excellent enantioselectivities by combination of chiral tert-butylsulfinimine chemistry with gold catalysis. Importantly, this represents the first example of a pyrrolidine synthesis from homopropargyl sulfonamide.

A Lewis acid-catalyzed alkyne oxidation strategy has been developed to produce diverse α-functionalized amides from readily and generally available ynamides. An efficient zinc(II)-catalyzed oxidative azidation and thiocyanation has been achieved, providing facile access to synthetically useful α-azido amides and α-thiocyanate amides, respectively. This chemistry can also be extended to oxidative halogenations by employing the 2-halopyridine N-oxide as both the oxidant and the halogen source, and its mechanistic rationale is also supported by density functional theory calculations. Moreover, NaBARF has been demonstrated to catalyze such an alkyne oxidation effectively, thus further excluding the metal carbene pathway in this cascade reaction.

A zinc-catalyzed oxidative reaction of ynamides with phenols and thiophenols under mild reaction conditions has been developed, which provides various α-aryloxy amides and α-arylthio amides in moderate to good yields, respectively. Importantly, high chemoselectivity is achieved by such a non-noble metal-catalyzed alkyne oxidation.

Superhydrophobic PDMS–HNTs (halloysite clay nanotubes) were prepared by the surface modification of purified HNTs (p-HNTs) with polydimethylsiloxane (PDMS). The strong hydrophobic properties and distinctive structure of PDMS–HNTs, resulting from the hollow and tubular structure of p-HNTs, have led to their use as supporting materials in the preparation of form-stable phase change material (PCM) composites, into which PCMs can be easily adsorbed and remain stable without leakage even at temperatures greater than the melting points of the PCMs. The PCMs were loaded at the outer and inner surfaces of PDMS–HNTs, and as a result of their incorporation, the latent heats of the PDMS–HNTs/PCMs composites were measured to be in the range of 44.7–72.1 kJ kg−1. Taking advantage of the simple process, low cost and excellent thermal stability, the PDMS–HNTs/PCM composites may have great potential for practical applications as solar energy storage systems.

The asymmetric synthesis of chiral γ-lactams is difficult and laborious; typically requiring pre-functionalization of starting materials. Now, a highly efficient alternative approach employing direct C−H amidation via chiral hydrogen-bond-donor catalysts has been developed.

Catalytic oxidation of alkynes by using pyridine N-oxides as external oxidants has proven to be a powerful tool in organic synthesis, allowing the assembly of functionalized carbocycles and heterocycles in a remarkably efficient manner. Recent progress in this area is reviewed with emphasis on metal-free or nonnoble-metal-catalyzed oxidative cyclizations.

To investigate gender differences of the associations between hyperuricemia and diabetic kidney disease (DKD) in elderly patients with type 2 diabetes mellitus (T2DM) based on electronic health records (EHR).A total of 20,207 older diabetic patients (mean age 71±7years) were investigated based on the EHR from 2012 to 2013 in the Minhang District of Shanghai-China. The status of hyperuricemia, albuminuric DKD and the odds ratios of DKD relative to hyperuricemia were analyzed among 8541 men and 11,666 women.The overall rate of hyperuricemia was 20.5% (males: 17.2%, females: 23.0%) and that of albuminuric DKD was 36.2% (males: 32.2%, female: 39.1%) in these diabetic patients. Hyperuricemia was independently associated with increased risk of reduced renal function and albuminuria (p0.001) in both genders. After adjustment of traditional DKD risk factors, hyperuricemia had a stronger association with albuminuric DKD in males (OR 1.67, 95% CI: 1.48-1.88) than in females (OR 1.23, 95% CI: 1.12-1.35).This study showed an independent association of hyperuricemia with albuminuric DKD that was stronger in elderly males for the first time in China based on EHR. The level of uric acid should be monitored and managed in older diabetic patients.

A novel zinc-catalyzed intermolecular oxidation of N-sulfonyl ynamides has been developed. A variety of functionalized α,β-unsaturated N-sulfonyl imides are readily accessed by utilizing this approach, thus providing a viable alternative to synthetically useful α,β-unsaturated imides. Importantly, the reaction is proposed to proceed by a vinyligous E2-type elimination pathway, but not metal carbene pathway.

An unprecedented gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles has been developed, allowing rapid and practical access to a wide range of synthetically useful 2-aminopyrroles., The generation of gold carbenes via the gold-catalyzed intermolecular reaction of nucleophiles containing relatively labile N–O or N–N bonds with alkynes has received considerable attention during recent years. However, this protocol is not atom-economic as the reaction produces a stoichiometric amount of pyridine or quinoline waste, the cleaved part of the N–O or N–N bonds. In this article, we disclose an unprecedented gold-catalyzed formal [3+2] cycloaddition between ynamides and isoxazoles, allowing rapid and practical access to a wide range of synthetically-useful 2-aminopyrroles. Most importantly, mechanistic studies and theoretical calculations revealed that this reaction presumably proceeds via an α-imino gold carbene pathway, thus providing a strategically novel, atom-economic route to the generation of gold carbenes. Other significant features of this approach include the use of readily-available starting materials, high flexibility, simple procedure, mild reaction conditions, and in particular, no need to exclude moisture or air (“open flask”).

Gold-catalyzed intermolecular alkyne oxidation by an N–O bond oxidant has proven to be a powerful method in organic synthesis during the past decade, because this approach would enable readily available alkynes as precursors in generating α-oxo gold carbenes. Among those, gold-catalyzed oxidative cyclization of dialkynes has received particular attention as this chemistry offers great potential to build structurally complex cyclic molecules. However, these alkyne oxidations have been mostly limited to noble metal catalysts, and, to our knowledge, non-noble metal-catalyzed reactions such as diyne oxidations have not been reported. Herein, we disclose a copper-catalyzed oxidative diyne cyclization, allowing the facile synthesis of a wide range of valuable pyrrolo[3,4-c]quinolin-1-ones. Interestingly, by employing the same starting materials, the gold-catalyzed cascade cyclization leads to the divergent formation of synthetically useful pyrrolo[2,3-b]indoles. Furthermore, the proposed mechanistic rationale for these cascade reactions is strongly supported by both control experiments and theoretical calculations., Fused N-heterocycles are structural motifs observed in natural products and bioactive compounds. Here, the authors developed divergent copper- and gold-catalyzed oxidative cyclizations of diynes to two types of tricyclic N-heterocycles and rationalized the product selectivity by theoretical calculations.

A concise and flexible synthesis of α,β-unsaturated amidines via gold-catalyzed intermolecular ynamide amination/carbene 1,2-shift between ynamides and benzylic azides has been developed. Under mild reaction conditions, various α,β-unsaturated amidines were obtained in mostly good yields, thus providing an efficient and atom-economic way for the construction of valuable α,β-unsaturated amidines.

Starting from readily available propargylic carboxylates, three sequential transformations [gold-catalyzed tandem reaction, scandium(III) trifluoromethanesulfonate catalyzed Nazarov cyclization, alkylation reaction] in a one-pot process led to the formation of cyclopentenone derivatives in excellent diastereoselectivities and moderate to good overall yields.

A novel gold-catalyzed 6-exo-dig cycloisomerization of o-propargylbiaryls has been developed that provides ready access to functionalized phenanthrenes in largely good to excellent yields. Notable features of this method are readily available starting materials, mild reaction conditions, and broad substrate scope.

The efficient intermolecular reaction of gold carbene intermediates, generated via gold-catalyzed alkyne oxidation, with indoles and anilines has been realized in aqueous media. Importantly, it was revealed for the first time that water could dramatically suppress the undesired over-oxidation, providing a general and practical solution to the problem of over-oxidation in gold-catalyzed intermolecular alkyne oxidation with external nucleophiles. This strategy was successfully applied to the formal synthesis of the Pfizer's chiral endothelin antagonist UK-350,926.

A gold-catalyzed intermolecular oxidation of chiral homopropargyl sulfonamides has been developed, which provides a reliable access to synthetically useful chiral pyrrolidin-3-ones with excellent ee, by combining the chiral tert-butylsulfinimine chemistry and gold catalysis. This methodology has also been used in the facile synthesis of natural product (-)-irniine. The use of readily available starting materials, a broad substrate scope, a simple procedure and the mild nature of this reaction render it a viable alternative for the synthesis of enantioenriched pyrrolidin-3-ones.

Skin is the first protection of human body. It is always challenged by a range of external factors, resulting in the wounds of skin. Hydrogel, as a dressing with multiple advantages, causes increasing interests or the applications in wound treatment. However, the function and importance of micro-environment of wound region are frequently neglected. In this study, we successfully developed a chemokine loaded biomimetic hydrogel as a functional reservoir to stimulate the rapid in situ recruitment of BMSCs for fast wound repair and regeneration. The biomimetic hydrogel was fabricated by using the Polyvinyl alcohol (PVA) combined with chitosan (CS) as the hybrid materials. The fabricated hydrogel possesses many features such as the porous structure, high swelling rate and moisture retention property. More importantly, the incorporated chemokine could be released with a sustained manner from the hydrogel and recruited the bone marrow mesenchymal stem cells (BMSCs) significantly both in vitro & in vivo. Moreover, the hydrogel was demonstrated to be highly biocompatible to the skin tissue without any side effect or irritation observed. Topical delivery of chemokine by the biomimetic PVA/CS hybrid material based hydrogel is demonstrated as a promising carrier to accelerate wound repair and regeneration without inducing scar formation and any other negative complications. The PVA/CS/SDF-1 hydrogel was shown a novel therapeutic system for wound therapy.

A concise gold-catalyzed method for the preparation of anthracenes from o-alkynyldiarylmethanes has been developed. Under mild reaction conditions, versatile anthracene derivatives were formed in moderate to good yields. The high flexibility, broad substrate scope, and mild nature of this reaction render it a viable alternative for the synthesis of anthracenes.

A gold-catalyzed tandem cycloisomerization/oxidation of homopropargyl amides has been developed, which provides ready access to synthetically useful chiral γ-lactams with excellent ee by combining the chiral tert-butylsulfinimine chemistry and gold catalysis. The utility of this methodology has also been demonstrated in the synthesis of biologically active compound S-MPP and natural product (-)-bgugaine. The use of readily available starting materials, a simple procedure, and mild reaction conditions are other significant features of this method.