Search Results (112)

Mechanochemical and transition-metal-catalyzed reactions of alkynes, exhibiting significant advantages like short reaction time, solvent-free, high yield and good selectivity, were considered to be green and sustainable pathways to access functionalized molecules and obtained increasing attention due to the superiorities of mechanochemical processes and the reactivities of alkynes. The ball milling and CuI-catalyzed Sonogashira coupling of alkyne and aryl iodide avoided the use of common palladium catalysts. The mechanochemical Rh(III)- and Au(I)-catalyzed C–H alkynylations of indoles formed the 2-alkynylated and 3-alkynylated indoles selectively. The mechanochemical and copper-catalyzed azide-alkyne cycloaddition (CuAAC) between alkynes and azides were developed to synthesize 1,2,3-triazoles. Isoxazole could be formed through ball-milling-enabled and Ru-promoted cycloaddition of alkyne and hydroxyimidel chloride. In this review, the generation of mechanochemical and transition-metal-catalyzed reactions of alkynes was highlighted. Firstly, the superiority and application of transition-metal-catalyzed reactions of alkynes were briefly introduced. After presenting the usefulness of green chemistry and mechanochemical reactions, mechanochemical and transition-metal-catalyzed reactions of alkynes were classified and demonstrated in detail. Based on different kinds of reactions of alkynes, mechanochemical and transition-metal-catalyzed coupling, cycloaddition and alkenylation reactions were summarized and the proposed reaction mechanisms were disclosed if available. Full article

Morquio A syndrome is a lysosomal disorder caused by the deficiency of the lysosomal enzyme N-acetylgalactosamine 6-sulfatase (GALNS, EC 3.1.6.4). Currently, enzyme replacement therapy (ERT) is used to treat Morquio A through the infusion of the recombinant enzyme VIMIZIM^® (elosulfase alfa, BioMarin). Unfortunately, the recombinant enzyme exhibits low conformational stability in vivo. A promising approach to address this issue is the coadministration of recombinant human GALNS (rhGALNS) with a pharmacological chaperone (PC), a molecule that selectively binds to the misfolded protein, stabilizes its conformation, and assists in the restoration of the impaired function. We report in this work the synthesis of a library of multivalent glycomimetics exploiting the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction between several dendrimeric scaffolds armed with terminal alkynes and azido ending iminosugars of different structures (pyrrolidines, piperidines, and pyrrolizidines) or simple azido ending carbohydrates as bioactive units. The biological evaluation identified pyrrolidine-based nonavalent dendrimers 1 and 36 as the most promising compounds, able both to bind the native enzyme with IC₅₀ in the micromolar range and to act as enzyme stabilizers toward rhGALNS in a thermal denaturation study, thus identifying promising compounds for a combined PC/ERT therapy. Full article

Tricyclic and tetracyclic lactone derivatives of thieno[2,3-b]pyrazine or thieno[2,3-b]quinoline, and 2H-pyrones were prepared using different methodologies. Pd/Cu-catalyzed Sonogashira coupling using Et₃N as a base, of methyl 7-bromothieno[2,3-b]pyrazine-6-carboxylate and (het)arylalkynes to yield the Sonogashira ester products, gave also the corresponding tricyclic lactones as minor products. However, the major products did not cyclize with TFA. Tricyclic lactones were then obtained by a tandem one-pot Sonogashira coupling and 6-endo-dig lactonization of 7-bromothieno[2,3-b]pyrazine-6-carboxylic acid with (het)arylalkynes, in good yields. Halogenated tricyclic lactones were synthesized by halocyclization using CuX and NXS. Tetracyclic lactones were synthesized through a Rh(III)-catalyzed formal [4+2] cycloaddition, between thieno[2,3-b]quinoline-2-carboxylic acid and internal alkynes, triggered by C-H activation, with the carboxylic group acting as a directing group. Using the SRB assay, the antitumor activity of both Sonogashira products and lactones was evaluated across five human cancer cell lines (CaCo-2, MCF-7, AGS, HeLa, NCI-H460). The best-performing compound was a Sonogashira product showing a GI₅₀ < 10 µM in all tumor cell lines and low toxicity in PLP2 cells. Additionally, antiparasitic testing against Trypanosoma brucei and Leishmania infantum revealed some compounds with IC₅₀ < 11 µM, though some level of cytotoxicity was observed in THP-1—derived macrophages. Full article

UDP-glycosyltransferases (UGTs) contribute to catalyzing the glycosylation of numerous functional natural products and novel derivatives with improved bioactivities. UDP-glucose sterol glucosyltransferase (SGT) is normally involved in the synthesis of sterol glycosides in a variety of organisms. SGT was derived from Salinispora tropica CNB-440 and heterologously expressed in Escherichia coli BL21 (DE3). Novel 12-O-glucosylginsenoside Rh2 was identified using HPLC, high-resolution MS (HR-MS), and NMR analysis. The cell viability assay was performed on 12-O-glucosylginsenoside-treated AGS stomach cancer, HeLa cervical cancer, U87MG glioma, and B16F10 melanoma cell lines. Protein structure modeling, molecular docking, and dynamics simulations were performed using AutoDock 4.2 and GROMACS 2020.1 software. The SGT gene is comprised of 1284 nucleotides and codes for 427 amino acids. The 12-O-glucosylginsenoside Rh2 may be a potential anticancer agent due to its potent viability inhibition of cancer cells. Structural analysis showed critical perspectives into the intermolecular interactions, stability, and binding energetics of the enzyme–ligand complex, with outcomes complementing the experimental data, thereby deepening our understanding of the structural basis of SGT-mediated glycosylation and its functional implications. This report presents a novel ginsenoside, 12-O-glucosylginsenoside Rh2, utilizing reshuffled SGT derived from S. tropica, and provides a promising candidate for anticancer drug research and development. Full article

A novel sequential one-pot bimetallic catalytic system combining Fe(III)-catalyzed alkynylation and a Rh(I)-catalyzed [2+2+2] reaction was successfully developed. The σ-Lewis acid properties of iron (III) and the π-Lewis acid properties of rhodium (I) catalysts were unified in an unprecedented intermolecular alkynylation/cyclotrimerization one-pot process. Using this unique Fe/Rh bimetallic relay catalytic system, a variety of benzo and pyrridinoisoindolinone derivatives were obtained under mild conditions from easily available N-(propargyl) hydroxy aminals, as the simplest N-acyliminium ion precursors, and several alkynes. Full article

In this work, we demonstrated that air-stable Ni(0) complexes with phosphine ligands can effectively catalyze intramolecular cyclotrimerization of a triyne to a compound with a [7]helical indeno[2,1-c]fluorene skeleton. The obtained results are comparable to those achieved by using Rh-based catalytic systems. Screening of the reaction conditions showed that bidentate phosphine ligands with small bite angles (70–80°) gave the best results in terms of yields. The highest asymmetric induction with the investigated air-stable Ni(0) precatalyst was obtained using the PROPHOS ligand in HFIP (62% ee). Other catalytic systems, like [Rh(CH₂=CH₂)₂Cl]₂ and [CpCo(P{OEt}₃)(trans-MeO₂CHC=CHCO₂Me)], have also been investigated, showing promising results. Full article

Recent developments in the synthesis of substituted polyacetylenes have considerably benefitted from advancements in organometallic catalysis; however, most important developments rely on the advent of Rh-catalyzed living polymerizations. The latter not only allow the tailoring of well-defined degrees of polymerization with low and narrow polydispersity but also enable access to stereochemical well-defined cis-transoidal polymers with a helical structure. These novel polymers open new avenues for application in photonics and electronics. Rh-catalyzed living polymerizations are mild and concise metal-catalyzed polymer syntheses that not only allow for the decoration of sidechains with multiple functionalities, including chiral units, but also enable enantioselective induction of helical chirality, memory of chirality, well-defined copolymerization, and end-group functionalization at both termini. This review summarizes recent developments in metal-catalyzed syntheses of substituted polyacetylenes, with a special focus on Rh-catalyzed living polymerizations. Full article

An efficient Rh(III)-catalyzed C-H activation of azobenzenes and subsequent [4+1] cascade annulation with CF₃-imidoyl sulfoxonium ylides was developed, yielding diverse CF₃-indazoles. This protocol featured easily available starting materials, excellent functional group tolerance and high efficiency. Moreover, the antitumor activities of selected CF₃-indazoles against human cancer cell lines were also studied, and the results indicated that several compounds displayed considerable antiproliferative activities. Full article

Efficient access to pyranoisoquinoline derivatives via rhodium-catalyzed double C-H functionalization of phenyl oxadiazoles and diazo compounds has been developed. Two C-C bonds and one C-O and C-N bond formation was realized by this tandem reaction, along with the formation of two heterocycles, affording diversified pyran-fused isoquinolines in moderate to good yields with broad functional group tolerance under mild reaction conditions. Full article

In the category of drugs approved by the U.S. FDA, pyrrolidine is the most frequently used core of five-membered nonaromatic heterocycles containing nitrogen. Herein, a Rh(II)/Pd(0) dual-catalyzed carbenoid N-H insertion/allylation cascade reaction has been developed. This protocol provide an efficient approach for the construction of diverse highly functionalized and polysubstituted pyrrolidines in high yields (up to 91%) with excellent chemoselectivities and high diastereoselectivities (>20:1) under mild reaction conditions. Full article

In mammals, the melatonin (Mel) concentration in the gastrointestinal tract is 400 times greater than in the pineal gland. However, the origin of Mel in the gastrointestinal tract and its role in reproductive regulation remains unclear. Therefore, we analyzed three potential Mel sources (feed, microorganisms, and the rumen wall) for their contribution to high Mel levels in the rumen and their biological effects. The feed contained high Mel concentrations, and Mel in rumen fluid and blood peaked two hours after feeding. Rumen microbial analysis showed a strong positive correlation between Mel and specific microbes, including Megasphaera, Butyrivibrio, Acetobacter, and Olsenella. In vitro experiments indicated that rumen microorganisms synthesized Mel from tryptophan. The rumen wall also contains key enzymes, AANAT and HIOMT, which catalyze Mel synthesis and membrane receptors MT1 and MT2 that mediate the function of Mel, suggesting that the rumen wall synthesizes Mel. Mel peaked in both rumen fluid and blood two hours after feeding. Feeding also altered blood levels of Mel, Gonadotropin-releasing hormone (GnRH), Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), progesterone (P4), and Estradiol (E2), with a correlation between Mel and fluctuations in GnRH, LH, P4, and E2 levels. Our findings suggest that feed is the primary source of high Mel levels in the rumen and impacts reproductive hormone fluctuations. This study elucidates the origin of high rumen Mel concentrations and reveals that food intake affects the natural secretion of various hormones, offering a new perspective on food sources for regulating reproductive physiology. Full article

Catalyzed by Rh₂(esp)₂ (10 mol%) and (±)-BINAP (20 mol%) in DCE at 80 °C, the cascade assembly between diazobarbiturates and alkylidene pyrazolones proceeded readily and produced spiro-furopyrimidines in 38–96% chemical yields. The chemical structure of the prepared spirofuro-pyrimidines was firmly confirmed by X-ray diffraction analysis. Full article

Hydroformylation of olefins is widely used in the chemical industry due to its versatility and the ability to produce valuable aldehydes with 100% atom economy. Herein, a hybrid phosphate promoter was found to efficiently promote rhodium-catalyzed hydroformylation of styrenes under remarkably mild conditions with high regioselectivities. Preliminary mechanistic studies revealed that the weak coordination between the Rhodium and the P=O double bond of this pentavalent phosphate likely induced exceptional reactivity and high ratios of branched aldehydes to linear products. Full article

The hydrogenation of C=C bonds in styrene−butadiene rubber (SBR), catalyzed by RhH(P(i-Pr)₃)₃, was experimentally investigated. Tris(triisopropylphosphine)hydridorhodium(I), RhH(P(i-Pr)₃)₃ (i-Pr=CH(CH₃)₂) was prepared by using rhodium chloride (RhCl₃), tetrahydrofuran (THF), triisopropylphosphine (P(i-Pr)₃) and a sodium mercury amalgam. The effect of catalyst/polymer ratio, reaction temperature, and hydrogen pressure on the reactivity of the catalytic system has been studied. The optimal experimental condition was obtained. The hydrogenated styrene-butadiene rubber (HSBR) was analyzed by FT-IR and ¹H-NMR. In the absence of any additives, the conversion of C=C bonds in SBR could easily reach 95% in a short period of time, and no obvious cross-linking was observed. The dynamic properties of SBR did not change after the hydrogenation of the unsaturated C=C bonds. A preliminary reaction mechanism was also proposed. This study provides a new route, not only for the chemical modification of SBR by using a rhodium complex but also for the hydrogenation of other unsaturated polymers, such as diene-based rubbers. Full article

An efficient method of accessing new CF₃-containing spiro-[indene-proline] derivatives has been developed based on a Cp*Rh(III)-catalyzed tandem C-H activation/[3+2]–annulation reaction of 5-aryl-2-(trifluoromethyl)-3,4-dihydro-2H-pyrrole-2-carboxylates with alkynes. An important feature of this spiro annulation process is the feasibility of dehydroproline moiety to act as a directing group in the selective activation of the aromatic C-H bond. Full article