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For developing novel photosensitizers with therapeutic potential in non-malignant and malignant cutaneous disorders, the unsymmetrical porphyrin, 5-(2-hydroxy-3-methoxyphenyl)-10, 15, 20-tris-(4-carboxymethylphenyl) porphyrin, was evaluated in silico and in vitro. The cellular uptake of the investigated porphyrin and its ability to perform photodynamic therapy were investigated in terms of the viability, proliferation, and necrosis of human HaCaT keratinocytes and human Hs27 skin fibroblasts, in correlation with the predictions regarding diffusion through cell membranes, ADMET profile (absorption, distribution, metabolism, elimination, toxicity), and potential pharmacological mechanism. Molecular docking and 250 ns molecular dynamics simulations revealed that P5.2 has the potential to form a relatively stable complex with the carbonic anhydrase IX catalytic site, the lowest predicted free energy of binding (MM/PBSA) being −39.097 kcal/mol. The results of the in vitro study showed that P5.2 is incorporated within 24 h in the investigated cells, especially in HaCaT keratinocytes, indicating its photosensitizing ability. Nevertheless, P5.2 does not exert significant cytotoxicity in "dark" conditions. In turn, PDT induced a decrease in the number of metabolically active HaCaT keratinocytes within 24 h, accompanied by a 4-fold increase in lactate dehydrogenase release, indicating its ability to perform PDT in human skin cells. The experimental results suggest that the asymmetrical porphyrin is a promising candidate theranostics agent for skin disorders. [ABSTRACT FROM AUTHOR]

Chirality plays a fundamental role in natural phenomena, yet its manifestation on solid surfaces remains relatively unexplored. In this study, we investigate the formation of chiroptical melanin‐based self‐assembled films on quartz substrates, leveraging mussel‐inspired surface chemistry. Water‐soluble porphyrins serve as molecular synthons, facilitating the spontaneous formation of hetero‐aggregates in phosphate‐buffered saline containing L‐ or D‐DOPA. Spectroscopic analysis reveals chiral transfer from DOPA enantiomers to porphyrin hetero‐aggregates, followed by the disruption of these latter and subsequent generation of chiral melanin structures in solution. Quartz substrates inserted into these solutions spontaneously accumulate homogeneous melanin‐like films over days, demonstrating the feasibility of self‐assembly. The resulting films exhibit characteristic UV/Vis and CD spectra, with distinct signals indicating successful chiral induction. Interestingly, the AFM characterizations reveal a distinct surface morphology, and in addition, some thermal and mechanical properties have been taken into account. Overall, this study sheds light on the formation, stability, and chiroptical properties of melanin‐based films, paving the way for their application in various fields. [ABSTRACT FROM AUTHOR]

Acyclic diaminocarbenes (ADCs)–Metal complex having strong donor ability and thermal stability led to extensive usability across every area of inorganic and organometallic chemistry. The unique properties of acyclic diaminocarbenes (ADCs) provide certain advantages over other carbene ligands and have the potential to make a great impact in catalysis. Further, the straightforward synthesis of M–ADCs (metal bound acyclic diaminocarbenes) complexes via metal-mediated reaction provides a wide range of well-defined metal carbene catalysts, which might inspire more researchers to devise unsymmetrically substituted, chiral, and novel acyclic carbene compounds. Although the above synthetic route is limited to a few late transition metals, but have great opportunities to expand the scope of this method. The application of M–ADCs complexes as a catalyst for several organic transformation reactions such as various cross-coupling reactions and asymmetric synthesis like hydroarylation, hydroazidation, hydroamination, cyclization and addition reactions which have shown comparable or even higher activities than the analogous M–NHCs based on all the reports presented. Recent findings of donor ability of several ADC ligands would be useful in fine-tuning the electronic properties, and then a catalyst with a certain combination of donicity and steric requirement could open new doors in catalytic reactivity. Thus, the objective of this review is to assess the recent growths that have been made in designing novel and chiral ADCs ligands and synthesizing ADCs–Metal complexes and to highlight catalytic activities of metal acyclic diaminocarbene complexes for cross-coupling reactions. [ABSTRACT FROM AUTHOR]

The relative configuration of the epoxide functionality in pinofuranoxin A (1), α-alkylidene-β-hydroxy-γ-methyl-γ-butyrolactone with trans-epoxy side chain isolated by Evidente et al. in 2021, was revised by DFT-based spectral reinvestigations and stereo-controlled synthesis. The present investigation demonstrates the difficulty of the configurational elucidation of the stereogenic centers on the conformationally flexible acyclic side-chains. Sharpless's enantioselective epoxidations and dihydroxylations were quite effective in the reinvestigations of the configurations. As our syntheses made all diastereomers available, these would be quite effective in the next structure-biological activity relationship studies. [ABSTRACT FROM AUTHOR]

Core-shell structured magnetic wrinkled organosilica-based metal-enzyme integrated catalysts were synthesized, and their catalytic performances were studied in the chemoenzymatic dynamic kinetic resolution of chiral amines in an organic solvent, as well as in the chemoenzymatic synthesis of chiral alcohols in water. Structure-performance studies revealed the important influence of their tunable structure and composition on the optimization of activity, stability, and recyclability in chemoenzymatic catalysis.

Abstract All living organisms produce only one enantiomer, so we found that all natural compounds are presented in enantiomerically pure form. Asymmetric synthesis is highly spread in medicinal chemistry because enantiomerically pure drugs are highly applicable. This study initially demonstrated the feasibility of a good idea for the asymmetric synthesis of α-alkylated carbonyl compounds with high enantiomeric purity ranging from 91 to 94% using different quinazolinone derivatives. The structure of all compounds was confirmed via elemental analysis and different spectroscopic data and the enantioselectivity was determined via HPLC using silica gel column. The synthesized compounds’ mode of action was investigated using molecular docking against the outer membrane protein A (OMPA) and exo-1,3-beta-glucanase, with interpreting their pharmacokinetics aspects. The results of the antimicrobial effectiveness of these compounds revealed that compound 6a has a broad biocidal activity and this in-vitro study was in line with the in-silico results. Overall, the formulated compound 6a can be employed as antimicrobial agent without any toxicity with high bioavailability in medical applications.

An unusual diastereodivergent stereoselective allylation reaction is presented. It consists of a palladium-catalyzed allylation reaction of an organocatalytically generated amino isobenzofulvene, where the diastereoselectivity is controlled by the electronic properties of a monodentate, achiral ligand on palladium. One major diastereoisomer is formed using triarylphosphines substituted with neutral or electron-donating substituents of the aryl group, while those with electron-withdrawing substituents favor the other diastereoisomer. The diastereoselectivity correlates with the Taft inductive parameter of substituents on the triarylphosphine ligand on palladium. The synergistic reaction involves both a catalytic secondary amine catalyst for the indene-aldehyde activation and the monodentate phosphine ligands on palladium, affording a highly enantioselective reaction with up to 98 % enantiomeric excess. Based on computational investigations, the role of the monodentate phosphine ligand on the diastereoselectivity is discussed.

Upgrading CO2 to value‐added chiral molecules via catalytic asymmetric C−C bond formation is a highly important yet challenging task. Although great progress on the formation of centrally chiral carboxylic acids has been achieved, catalytic construction of axially chiral carboxylic acids with CO2 has never been reported to date. Herein, we report the first catalytic asymmetric synthesis of axially chiral carboxylic acids with CO2, which is enabled by nickel‐catalyzed dynamic kinetic asymmetric reductive carboxylation of racemic aza‐biaryl triflates. A variety of important axially chiral carboxylic acids, which are valuable but difficult to obtain via catalysis, are generated in an enantioconvergent version. This new methodology features good functional group tolerance, easy to scale‐up, facile transformation and avoids cumbersome steps, handling organometallic reagents and using stoichiometric chiral materials. Mechanistic investigations indicate a dynamic kinetic asymmetric transformation process induced by chiral nickel catalysis. [ABSTRACT FROM AUTHOR]

Herein, we present a unified chemical synthesis of three subgroups of cephalotaxus diterpenoids. Key to the success lies in adopting a synthetic strategy that is inspired by biosynthesis but is opposite in nature. By employing selective one‐carbon introduction and ring expansion operations, we have successfully converted cephalotane‐type C18 dinorditerpenoids (using cephanolide B as a starting material) into troponoid‐type C19 norditerpenoids and intact cephalotane‐type C20 diterpenoids. This synthetic approach has enabled us to synthesize cephinoid H, 13‐oxo‐cephinoid H, 7‐oxo‐cephinoid H, fortalpinoid C, 7‐epi‐fortalpinoid C, cephanolide E, and 13‐epi‐cephanolide E. Furthermore, through the development of an intermolecular asymmetric Michael reaction between β‐oxo esters and β‐substituted enones, we have achieved the enantioselective synthesis of advanced intermediates within our synthetic sequence, thus formally realizing the asymmetric total synthesis of the cephalotaxus diterpenoids family. [ABSTRACT FROM AUTHOR]

Upgrading CO2 to value‐added chiral molecules via catalytic asymmetric C−C bond formation is a highly important yet challenging task. Although great progress on the formation of centrally chiral carboxylic acids has been achieved, catalytic construction of axially chiral carboxylic acids with CO2 has never been reported to date. Herein, we report the first catalytic asymmetric synthesis of axially chiral carboxylic acids with CO2, which is enabled by nickel‐catalyzed dynamic kinetic asymmetric reductive carboxylation of racemic aza‐biaryl triflates. A variety of important axially chiral carboxylic acids, which are valuable but difficult to obtain via catalysis, are generated in an enantioconvergent version. This new methodology features good functional group tolerance, easy to scale‐up, facile transformation and avoids cumbersome steps, handling organometallic reagents and using stoichiometric chiral materials. Mechanistic investigations indicate a dynamic kinetic asymmetric transformation process induced by chiral nickel catalysis. [ABSTRACT FROM AUTHOR]

Chirality constitutes an inherent attribute of nature. The catalytic asymmetric synthesis of molecules with central, axial, and helical chirality is a topic of intense interest and is becoming a mature field of research. However, due to the difficulty in synthesis and the lack of a prototype, less attention has been given to planar chirality arising from the destruction of symmetry on a single planar ring. Herein, we report the catalytic asymmetric synthesis of planar-chiral dianthranilides, a unique class of tub-shaped eight-membered cyclic dilactams. This protocol is enabled by cinchona alkaloid-catalyzed (dynamic) kinetic resolution. Under mild conditions, various C2- or C1-symmetric planar-chiral dianthranilides have been readily prepared in high yields with excellent enantioselectivity. These dianthranilides can serve as an addition to the family of planar-chiral molecules. Its synthetic value has been demonstrated by kinetic resolution of racemic amines via acyl transfer, enantiodivergent synthesis of the natural product eupolyphagin, and preliminary antitumor activity studies. Chirality has long fascinated chemists, but asymmetric synthesis has largely focused on central, axial, and helical chirality to date. Here, the authors synthesize dianthranilides with planar chirality, via cinchona alkaloid-catalyzed (dynamic) kinetic resolution. [ABSTRACT FROM AUTHOR]

Upgrading CO2 to value‐added chiral molecules via catalytic asymmetric C−C bond formation is a highly important yet challenging task. Although great progress on the formation of centrally chiral carboxylic acids has been achieved, catalytic construction of axially chiral carboxylic acids with CO2 has never been reported to date. Herein, we report the first catalytic asymmetric synthesis of axially chiral carboxylic acids with CO2, which is enabled by nickel‐catalyzed dynamic kinetic asymmetric reductive carboxylation of racemic aza‐biaryl triflates. A variety of important axially chiral carboxylic acids, which are valuable but difficult to obtain via catalysis, are generated in an enantioconvergent version. This new methodology features good functional group tolerance, easy to scale‐up, facile transformation and avoids cumbersome steps, handling organometallic reagents and using stoichiometric chiral materials. Mechanistic investigations indicate a dynamic kinetic asymmetric transformation process induced by chiral nickel catalysis. [ABSTRACT FROM AUTHOR]

Upgrading CO2 to value‐added chiral molecules via catalytic asymmetric C−C bond formation is a highly important yet challenging task. Although great progress on the formation of centrally chiral carboxylic acids has been achieved, catalytic construction of axially chiral carboxylic acids with CO2 has never been reported to date. Herein, we report the first catalytic asymmetric synthesis of axially chiral carboxylic acids with CO2, which is enabled by nickel‐catalyzed dynamic kinetic asymmetric reductive carboxylation of racemic aza‐biaryl triflates. A variety of important axially chiral carboxylic acids, which are valuable but difficult to obtain via catalysis, are generated in an enantioconvergent version. This new methodology features good functional group tolerance, easy to scale‐up, facile transformation and avoids cumbersome steps, handling organometallic reagents and using stoichiometric chiral materials. Mechanistic investigations indicate a dynamic kinetic asymmetric transformation process induced by chiral nickel catalysis. [ABSTRACT FROM AUTHOR]

The enantioselective synthesis of S-stereogenic sulfinamides has garnered considerable attention due to their structural and physicochemical properties. However, catalytic asymmetric synthesis of sulfinamides still remains daunting challenges, impeding their broad application in drug discovery and development. Here, we present an approach for the synthesis of S-stereogenic sulfinamides through peptide-mimic phosphonium salt-catalyzed asymmetric skeletal reorganization of simple prochiral and/or racemic sulfoximines. This methodology allows for the facile access to a diverse array of substituted sulfinamides with excellent enantioselectivities, accommodating various substituent patterns through desymmetrization or parallel kinetic resolution process. Mechanistic experiments, coupled with density functional theory calculations, clarify a stepwise pathway involving ring-opening and ring-closing processes, with the ring-opening step identified as crucial for achieving stereoselective control. Given the prevalence of S-stereogenic centers in pharmaceuticals, we anticipate that this protocol will enhance the efficient and precise synthesis of relevant chiral molecules and their analogs, thereby contributing to advancements in drug discovery. The enantioselective synthesis of S-stereogenic sulfinamides has garnered considerable attention due to their unique structural and physicochemical properties but catalytic asymmetric synthesis of sulfinamides still remains challenging. Here, the authors present the synthesis of S-stereogenic sulfinamides through the peptide-mimic phosphonium salt-catalyzed asymmetric skeletal reorganization of simple prochiral and racemic sulfoximines. [ABSTRACT FROM AUTHOR]

Chiral trisubstituted vicinal diols are a type of important organic compounds, serving as both common structure units in bioactive natural products and chiral auxiliaries in asymmetric synthesis. Herein, by using siloxypropadienes as the precursors of allyl copper(I) species, a copper(I)‐catalyzed diastereoselective and enantioselective reductive allylation of ketones was achieved, providing both syn‐diols and anti‐diols in good to excellent enantioselectivity. DFT calculations show that cis‐γ‐siloxy‐allyl copper species are generated favorably with either 1‐TBSO‐propadiene or 1‐TIPSO‐propadiene. Moreover, the steric difference of TBS group and TIPS group distinguishes the face selectivity of acetophenone, leading to syn‐selectivity for 1‐TBSO‐propadiene and anti‐selectivity for 1‐TIPSO‐propadiene. Easy transformations of the products were performed, demonstrating the synthetic utility of the present method. Moreover, one chiral diol prepared in the above transformations was used as a suitable organocatalyst for the catalytic asymmetric reductive self‐coupling of aldimines generated in situ with B2(neo)2. [ABSTRACT FROM AUTHOR]

All living organisms produce only one enantiomer, so we found that all natural compounds are presented in enantiomerically pure form. Asymmetric synthesis is highly spread in medicinal chemistry because enantiomerically pure drugs are highly applicable. This study initially demonstrated the feasibility of a good idea for the asymmetric synthesis of α-alkylated carbonyl compounds with high enantiomeric purity ranging from 91 to 94% using different quinazolinone derivatives. The structure of all compounds was confirmed via elemental analysis and different spectroscopic data and the enantioselectivity was determined via HPLC using silica gel column. The synthesized compounds' mode of action was investigated using molecular docking against the outer membrane protein A (OMPA) and exo-1,3-beta-glucanase, with interpreting their pharmacokinetics aspects. The results of the antimicrobial effectiveness of these compounds revealed that compound 6a has a broad biocidal activity and this in-vitro study was in line with the in-silico results. Overall, the formulated compound 6a can be employed as antimicrobial agent without any toxicity with high bioavailability in medical applications. [ABSTRACT FROM AUTHOR]

The synthesis of chiral succinimides bearing all‐carbon quaternary stereocenters at the C3 position is important, but remains challenging. The present work demonstrates conjugate additions with catalysis by a chiral 1,10‐phenanthroline‐Pd complex (L1‐PdCl2) that exhibit complete regioselectivity with a high degree of enantioselectivity. These reactions afford chiral 3,3‐disubstituted succinimides having all‐carbon quaternary stereocenters with 40–99% ee. Importantly, chiral 3,3‐diaryl succinimides could also be obtained in 35–98% yields and 40–99% ee. Moreover, the present L1‐PdCl2‐catalyzed asymmetric conjugate addition could be performed on the gram scale and was also used to introduce such stereocenters into bioactive molecules. [ABSTRACT FROM AUTHOR]

Vinylcyclopropanes (VCPs) are important building blocks with multifaceted reactivity. Catalytic asymmetric ring opening of vinylcyclopropanes is a highly efficient process to access valuable chiral molecules with diverse functionalities that can be further functionalized for a series of synthetic purposes. VCPs are very well‐known substrates for cycloaddition reactions and this chemistry has been widely explored. On the contrary, despite of enormous synthetic potential, development of new innovative strategies for the catalytic, asymmetric ring opening of VCPs is somewhat underdeveloped. Recently, several significant examples have emerged in the literature for various asymmetric ring opening of both activated and unactivated vinylcyclopropanes that involve transition metal catalysis. These developments are relevant additions to the vinylcyclopropane chemistry. In this review, we aim to summarize all the catalytic asymmetric ring opening transformations reported till date and provide a comprehensive analysis of these research outcomes. [ABSTRACT FROM AUTHOR]

Crambescin B decarboxylate is an inhibitor of voltage‐gated sodium channels and a potential biochemical tool. Herein, we report the asymmetric total synthesis of crambescin B decarboxylate using a new synthetic strategy. The key aspects of this new protocol include: 1) the use of an optically pure epoxide, synthesized by the Jacobsen hydrolytic kinetic resolution, as the starting material for guanidino‐aziridine, and 2) the introduction of the THF ring through nucleophilic substitution using an acyl anion equivalent. The synthetic protocol reported herein is nine steps shorter than the previously reported shortest method. We determined the cytotoxicity and protective effects of crambescin B decarboxylate in mouse‐hippocampus‐derived neuronal HT22 cells with an MTS assay. Cell viability was observed to decrease in a concentration‐dependent manner without cell detachment or shrinkage. In addition, crambescin B decarboxylate protected glutamate‐induced cell death. [ABSTRACT FROM AUTHOR]

Sulfoxides are remarkably useful in asymmetric synthesis and drug development. Herein, we propose a new electroenzymatic cascade route to selectively synthesize methyl phenyl sulfoxide rather than methyl phenyl sulfone by the oxidation of thioanisole. Chloroperoxidase (CPO) functionalized with 1-ethyl-3-methylimidazolium bromide (ILEMB) is encapsulated into dendritic N-doped mesoporous carbon nanospheres (NMCNs) modified with polyethyleneimine (NMCNs-PEI) to form a biohybrid (CPO-ILEMB@NMCNs-PEI). The in situ generation of hydrogen peroxide (H2O2) species by the two-electron oxygen reduction reaction (2e−ORR) on NMCNs-PEI initiates the subsequent selective oxidation of thioanisole by CPO-ILEMB. NMCNs-PEI shows not only high electroactivity for the 2e−ORR but also good biocompatibility for CPO-ILEMB immobilization. The mesopores in NMCNs-PEI can provide a protective space for the encapsulated enzyme, ensuring the operational stability of the enzyme and avoiding the escape of H2O2, which result in high catalytic activity. The experimental results suggest that the catalytic efficiency of the electroenzymatic cascade system with the CPO-ILEMB@NMCNs-PEI biohybrid is up to 4.5 times higher than that of the free CPO-ILEMB catalytic system with H2O2 generated by NMCNs-PEI for the oxidation of thioanisole to produce methyl phenyl sulfoxide. [ABSTRACT FROM AUTHOR]

Stereoselective construction of g- and d-stereocenters in carbonyl compounds is a pivotal objective in asymmetric synthesis. Here, we report chiral bifunctional oxazoline-pyridone ligands that enable enantioselective palladium-catalyzed remote g-C−H (hetero)arylations of free cycloalkane carboxylic acids, which are essential carbocyclic building blocks in organic synthesis. The reaction establishes g-tertiary and a-quaternary stereocenters simultaneously in up to >99% enantiomeric excess, providing access to a wide range of cyclic chiral synthons and bioactive molecules. The sequential enantioselective editing of two methylene C-H bonds can be achieved by using chiral ligands with opposite configuration to construct carbocycles containing three chiral centers. Enantioselective remote d-C−H (hetero)arylation is also realized to establish d-stereocenters that are particularly challenging to access using classical methodologies. [ABSTRACT FROM AUTHOR]

This article explores the development of a method for the asymmetric β-borylation of α,β-unsaturated acyl silanes using copper catalysis. The authors conducted experiments to optimize the reaction conditions and found that a ligand-free reaction produced the best results. They also investigated the range of the reaction and successfully synthesized various β-boryl acyl silanes with different substituents. The authors suggest that the inclusion of Li(acac) helps prevent undesired cleavage of the acyl silane moiety. Overall, this research provides valuable insights into the optimization and scope of a Cu I -catalyzed conjugate borylation reaction, which may have potential applications in further studies of bifunctional molecules. [Extracted from the article]

New chiral ligands could be obtained by introducing proline moieties and imidazoline moieties to binaphthyl skeletons. The chiral ligands exhibited balanced rigidity and flexibility which could allow the change of the conformations during the reactions on one hand, and could provide sufficient asymmetric induction on the other. The proline moiety could act as a linker connecting the binaphthyl skeletons and the imidazoline moieties as well as a coordinating group for the central metal, and the electronic and steric properties of the imidazoline groups could be carefully fine‐tuned by the use of different substituents. In the presence of Cu(II) catalyst bearing such chiral ligands, aza‐Friedel–Crafts reaction of 1‐naphthols and electron‐rich phenols with isatin‐derived ketimines provided the desired products with good to excellent yields and up to 99 % ee. The reactions showed good scalability, and excellent ee could still be obtained when the reaction was carried out in gram‐scale. [ABSTRACT FROM AUTHOR]

In this study, the design and asymmetric synthesis of a series of chiral targets of orientational chirality were conducted by taking advantage of N-sulfinylimine-assisted nucleophilic addition and modified Sonogashira catalytic coupling systems. Orientational isomers were controlled completely using alkynyl/alkynyl levers [C(sp)-C(sp) axis] with absolute configuration assignment determined by X-ray structural analysis. The key structural element of the resulting orientational chirality is uniquely characterized by remote through-space blocking. Forty examples of multi-step synthesis were performed, with modest to good yields and excellent orientational selectivity. Several chiral orientational amino targets are attached with scaffolds of natural and medicinal products, showing potential pharmaceutical and medical applications in the future. [ABSTRACT FROM AUTHOR]

A series of novel thio-derivatives of d-glucosamine has been synthesized using double inversion procedures at the C3 atom. New compounds were applied as ligands for the diethylzinc addition to benzaldehyde and the products of the addition were obtained with a low to good enantiomeric ratio. The direction and the level of the asymmetric induction were highly dependent on the type of protecting groups on the nitrogen and sulfur atoms. [ABSTRACT FROM AUTHOR]

Microgel-enhanced asymmetric hydrogels containing a thermosensitive layer and a non-thermosensitive layer are constructed. Actuators exhibiting outstanding response properties and multiple mechanosensors possessing high sensitivity are demonstrated. [Display omitted] Thermosensitive hydrogels have found extensive applications in soft devices, but they often suffer from limited functionalities, low response rate and small response amplitude. In this work, double layered asymmetrical hydrogels composed of a thermosensitive layer and a non-thermosensitive layer are developed to simultaneously achieve high-performance mechanosensing and actuating properties in a single hydrogel. In thermosensitive layer, thermosensitive microgels are introduced to construct hierarchical structure, which accounts for the enhanced thermosensitive behaviors by cooperative responsiveness. In non-thermosensitive layer, poly(acrylamide- co -acrylic acid) (P(AM- co -AA)) hydrogel is constructed. KCl is introduced as conductive component. Mechanosensors for monitoring various mechanical stimuli in daily life have been fabricated utilizing such hydrogels and high gauge factors (GF) have been achieved, 0.38 for resistive strain sensors, 9.40 kPa−1 for piezoresistive pressure sensors and 3.92 kPa−1 for capacitive pressure sensors. Because of the asymmetrical structure, such hydrogels also exhibit outstanding actuating properties with a fast response rate of 863°/min and a bending amplitude about 360°. Interestingly, grasping-releasing of target objects utilizing an octopus-shaped hydrogel actuator and temperature alerting based on hydrogel actuator are also demonstrated. Overall, the double layered asymmetrical ionic hydrogels have provided a new clue to construct hydrogel devices with multiple functionalities and enhanced response properties. [ABSTRACT FROM AUTHOR]

The construction of silicon‐stereogenic silanols via Pd‐catalyzed intermolecular C−H alkenylation with the assistance of a commercially available L‐pyroglutamic acid has been realized for the first time. Employing oxime ether as the directing group, silicon‐stereogenic silanol derivatives could be readily prepared with excellent enantioselectivities, featuring a broad substrate scope and good functional group tolerance. Moreover, parallel kinetic resolution with unsymmetric substrates further highlighted the generality of this protocol. Mechanistic studies indicate that L‐pyroglutamic acid could stabilize the Pd catalyst and provide excellent chiral induction. Preliminary computational studies unveil the origin of the enantioselectivity in the C−H bond activation step. [ABSTRACT FROM AUTHOR]

Herein, multiple types of chiral Os(II) complexes have been designed to address the appealing yet challenging asymmetric C(sp3)−H functionalization, among which the Os(II)/Salox species is found to be the most efficient for precise stereocontrol in realizing the asymmetric C(sp3)−H amidation. As exemplified by the enantioenriched pyrrolidinone synthesis, such tailored Os(II)/Salox catalyst efficiently enables an intramolecular site‐/enantioselective C(sp3)−H amidation in the γ‐position of dioxazolone substrates, in which benzyl, propargyl and allyl groups bearing various substituted forms are well compatible, affording the corresponding chiral γ‐lactam products with good er values (up to 99 : 1) and diverse functionality (>35 examples). The unique performance advantage of the developed chiral Os(II)/Salox system in terms of the catalytic energy profile and the chiral induction has been further clarified by integrated experimental and computational studies. [ABSTRACT FROM AUTHOR]

We have achieved the first total synthesis of pallamolides A−E. Of these compounds, pallamolides B−E possess intriguing tetracyclic skeletons with novel intramolecular transesterifications. Key transformations include highly diastereoselective sequential Michael addition reactions to construct the bicyclo[2.2.2]octane core with the simultaneous generation of two quaternary carbon centers, a one‐pot SmI2‐mediated intramolecular ketyl–enoate cyclization/ketone reduction to generate the key oxabicyclo[3.3.1]nonane moiety, and an acid‐mediated deprotection/oxa‐Michael addition/β‐hydroxy elimination cascade sequence to assemble the tetracyclic pallamolide skeleton. Kinetic resolution of ketone 14 through Corey–Bakshi–Shibata reduction enabled the asymmetric synthesis of pallamolides A−E. [ABSTRACT FROM AUTHOR]

Strong light‐matter interaction is emerging as an exciting tool for controlling chemical reactions. Here, we demonstrate an L‐proline‐catalyzed direct asymmetric Aldol reaction under vibrational strong coupling. Both the reactants (4‐nitrobenzaldehyde and acetone) carbonyl bands are coupled to an infrared photon and react in the presence of L‐proline. The reaction mixture is eluted from the cavity, and the conversion yields and enantiomeric excess are quantified using NMR and chiral HPLC. The conversion yields increase by up to 90 % in ON‐resonance conditions. Interestingly, a large increase in the conversion yield does not affect the enantiomeric excess. Further control experiments were carried out by varying the temperature, and we propose that the rate‐limiting step may not be the deciding factor in enantioselectivity. Whereas the formation of the enamine intermediate is modified by cavity coupling experiments. For this class of enantioselective reactions, strong coupling does not change the enantiomeric excess, possibly due to the large energy difference in chiral transition states. Strong coupling can boost the formation of enamine intermediate, thereby favouring the product yield. This gives more hope to test polaritonic chemistry based on enantioselective reactions in which the branching ratios can be controlled. [ABSTRACT FROM AUTHOR]

Described herein is the successful crystallization‐induced dynamic resolution (CIDR) of an α‐lithiated phosphine borane utilizing the easily accessible and inexpensive ligand (R,R)‐TMCDA. Starting from the essential P‐prochiral building block dimethyl phenyl phosphine borane we were able to obtain phosphine boranes in yields up to 80 % and e.r. up to 98 : 2 by crystallization of the lithiated intermediate prior to the trapping reaction. NMR‐based deuterium labeling experiments indicate that the epimerization in solution is based on the intermolecular proton transfer between nonlithiated phosphine borane and the corresponding lithiated intermediate, rendering the presence of the remaining starting compound in an optimized solvent mixture the main factor for successful enantioselective synthesis. Quantum chemical calculations using different model systems based on solid state structures confirm these experimental results. By gaining insights into the epimerization mechanism, essential principles for CIDR of lithiated phosphine boranes are elucidated that may be expanded to other important P‐stereogenic compounds and simple chiral amines. [ABSTRACT FROM AUTHOR]

DAT2 is a member of the diacyl trehalose family (DAT) of antigenic glycolipids located in the mycomembrane of Mycobacterium tuberculosis (Mtb). Recently it was shown that the molecular structure of DAT2 had been incorrectly assigned, but the correct structure remained elusive. Herein, the correct molecular structure of DAT2 and its methyl‐branched acyl substituent mycolipanolic acid is determined. For this, four different stereoisomers of mycolipanolic acid were prepared in a stereoselective and unified manner, and incorporated into DAT2. A rigorous comparison of the four isomers to the DAT isolated from Mtb H37Rv by NMR, HPLC, GC, and mass spectrometry allowed a structural revision of mycolipanolic acid and DAT2. Activation of the macrophage inducible Ca2+‐dependent lectin receptor (Mincle) with all four stereoisomers shows that the natural stereochemistry of mycolipanolic acid / DAT2 provides the strongest activation, which indicates its high antigenicity and potential application in serodiagnostics and vaccine adjuvants. [ABSTRACT FROM AUTHOR]

General, catalytic and enantioselective construction of chiral α,α-dialkyl indoles represents an important yet challenging objective to be developed. Herein we describe a cobalt catalyzed enantioselective anti-Markovnikov alkene hydroalkylation via the remote stereocontrol for the synthesis of α,α-dialkyl indoles and other N-heterocycles. This asymmetric C(sp3)−C(sp3) coupling features high flexibility in introducing a diverse set of alkyl groups at the α-position of chiral N-heterocycles. The utility of this methodology has been demonstrated by late-stage functionalization of drug molecules, asymmetric synthesis of bioactive molecules, natural products and functional materials, and identification of a class of molecules exhibiting anti-apoptosis activities in UVB-irradiated HaCaT cells. Ligands play a vital role in controlling the reaction regioselectivity. Changing the ligand from bi-dentate L6 to tridentate L12 enables CoH-catalyzed Markovnikov hydroalkylation. Mechanistic studies disclose that the anti-Markovnikov hydroalkylation involves a migratory insertion process while the Markovnikov hydroalkylation involves a MHAT process. Catalytic and enantioselective construction of chiral α,α-dialkyl indoles represents an important yet challenging objective to be developed. Herein the authors describe a cobalt catalyzed enantioselective anti-Markovnikov alkene hydroalkylation via the remote stereocontrol for the synthesis of α,α-dialkyl indoles and other N-heterocycles. [ABSTRACT FROM AUTHOR]

A stereoselective Biginelli reaction involving a CH‐active podand, thiourea, and benzaldehyde was carried out using C2‐symmetric bis(hydroxy)proline‐containing amides as chiral inducers. The target dihydropyrimidinethione‐containing podand was obtained with an enantiomeric excess of 65–75 % and a yield of 58 % under mild conditions. It was established that in the process of asymmetric induction the value of ee depended on the presence of OH group in the proline fragment and of the linker structure in the chiral inducer molecule, in particular, on the presence of asymmetric carbon atoms and the movability of the single bond between them in the linker itself. Based on experimental data, one of the probable reaction mechanisms confirming the special role of the L‐proline or trans‐4‐hydroxyproline fragments in asymmetric induction has been proposed. The developed technique for obtaining an active tuberculostatic agent expands the possibilities for using C2‐symmetric chiral inducers in asymmetric catalysis and is of interest for the synthesis of enantiomerically pure compounds of similar structure. [ABSTRACT FROM AUTHOR]

An efficient N‐heterocyclic carbene (NHC)‐catalyzed kinetic resolution of 2‐substituted 3‐nitro‐1,2‐dihydroquinolines (DHQs) allowing the synthesis of densely functionalized enantioenriched tetrahydroquinolines through the resolution at remote stereocenter is described. The Re‐face addition of α,β‐unsaturated azolium homoenolate intermediate generated in situ from enal with the more kinetically favored (S)‐enantiomer of the racemic 2‐substituted 3‐nitro‐1,2‐dihydroquinolines (rac‐1), affording the enantiopure tetrahydroquinolines (up to >99 : 1 dr, >99 : 1 er) and the opposite (R)‐enantiomer of DHQ (ent‐1) was recovered (up to >99 : 1 er). [ABSTRACT FROM AUTHOR]

we establish a relay catalysis strategy utilizing Pd(OAc)2/chiral phosphoric acid catalyst for the efficient synthesis of optically active 2-phenyl tetrahydroquinoline via a one-pot three-step domino reaction of 2-iodoaniline with allylic alcohol, eliminating the need for intermediate isolation. Compared to conventional single catalysis methods, this cooperative relay catalysis offers advantages of simplicity and high efficiency. Introducing scientific frontiers such as cooperative relay catalysis into experimental teaching, along with principles of green chemistry and energy saving, broadens students' scientific perspectives, ignites their passion for learning, and enhances their innovation capabilities. Furthermore, this experiment encompasses fundamental theoretical knowledge including Grignard reactions, Heck reactions, imine condensations, and asymmetric hydrogen transfers, alongside practical analytical techniques such as thin-layer chromatography (TLC), column chromatography, nuclear magnetic resonance (NMR), rotary evaporation, high-performance liquid chromatography (HPLC), and polarimetry. Through this comprehensive experiment, students' theoretical understanding, experimental skills, and scientific reasoning abilities are enriched, fostering the integration of scientific research and teaching. [ABSTRACT FROM AUTHOR]

Steric hindrance in Lewis acid (LA) and Lewis base (LB) obstruct the Lewis acid–base adduct formation, and the pair was termed as frustrated Lewis pair (FLP). In the past 16 years, the field of enantioselective catalysis by chiral FLPs has been slowly growing. It was shown that chiral LAs are significant as they are involved in the hydrogen transfer (HT) step to the imine, resulting in enantioselectivity. After H2 activation, the borohydride can exist in a number of plausible conformations and their stability is governed by the presence of noncovalent interaction through C–H····π and π····π interactions. However, LBs are not ideal for asymmetric induction as they compete with the imine substrate as a counter LB. Further, the proton transfer from chiral LB to the imine does not induce any chirality as chirality develops in the HT step. However, intramolecular FLPs with chiral scaffold are very efficient as they possess an optimum distance between LA and LB, which facilitates the H2 activation but precludes the adduct formation of the small molecules substrate with the LA component. This mini‐review summarizes computational investigation involving chiral LA and LB, and discusses intramolecular FLPs in the enantioselective catalysis. [ABSTRACT FROM AUTHOR]

A concise synthesis of the sex pheromones of elm spanworm as well as painted apple moth has been achieved. The key steps were the alkylation of acetylide ion, Sharpless asymmetric epoxidation and Brown's P2-Ni reduction. This approach provided the sex pheromone of the elm spanworm (1) in 31% total yield and those of the painted apple moth (2, 3) in 26% and 32% total yields. The ee values of three final products were up to 99%. The synthesized pheromones hold promising potential for use in the management and control of these pests. [ABSTRACT FROM AUTHOR]

Tris(hydroxymethyl)phosphine oxide, (HOCH2)3PO (THPO), is recognized as an efficient flame-retardant polyol and a derivative of PH3 – an environment-friendly, halogen-free source for phosphorus compounds and polymers. Synthesis and industrial production of THPO are based on straightforward oxidation of tris(hydroxymethyl)phosphine, (HOCH2)3P (THP), or neutralized tetrakis(hydroxymethyl)phosphonium chloride (THPC), or sulfate (THPS), by air/O2 or H2O2. In alkaline aqueous media, THP is oxidized by water with liberation of H2. As an alcohol, THPO readily reacts with isocyanates, epoxides, aziridines, and carboxylic acid derivatives, and is widely used as crosslinker or chain-extender to produce flame-retardant polyurethanes, polyethers, polyesters, and composite materials. Similarly, with compounds containing E–Cl bonds (E = P, Si, and S), THPO forms a variety of flame-retardant P/E-compounds or polymers. Condensation of THPO with phenols proceeds via cleavage of a P–C bond of THPO and liberation of CH2O that leads to flame-retardant THPO-phenol resins. With functionalized alkyl halides, THPO forms tris(alkoxymethyl)phosphine oxide monomers containing, for example, pendant allyl, propargyl, or silane groups. Halogenation of THPO leads to tris(chloromethyl)phosphine oxide, (ClCH2)3PO, or tris(bromomethyl)phosphine oxide, (BrCH2)3PO, useful for syntheses of multifunctional organophosphorus compounds, for example, tris(aminomethyl)phosphine oxide, (NH2CH2)3PO, and phosphorus-containing podands. Similar to THPO, tris(hydroxymethyl)phosphine sulfide, (HOCH2)3PS, is used in preparation of flame-retardant components for polymers, and, in synthesis of asymmetric phosphorus compounds. [ABSTRACT FROM AUTHOR]

A self-sufficient bifunctional enzyme integrating reductive amination and coenzyme regeneration activities was developed and successfully employed to synthesize (S)-cyclopropylglycine with an improved reaction rate 2.1-fold over the native enzymes and a short bioconversion period of 6 h at a high substrate concentration of 120 g·L−1 and space–time yield of (S)-cyclopropylglycine up to 377.3 g·L−1·d−1, higher than that of any previously reported data. Additionally, (S)-cyclopropylglycine could be continuously synthesized for 90 h with the enzymes packed in a dialysis tube, providing 634.6 g of (S)-cyclopropylglycine with >99.5% ee and over 95% conversion yield up to 12 changes. These results confirmed that the newly developed NADH-driven biocatalytic system could be utilized as a self-sufficient biocatalyst for industrial application in the synthesis of (S)-cyclopropylglycine, which provides a chiral center and cyclopropyl fragment for the frequent synthesis of preclinical/clinical drug molecules. [ABSTRACT FROM AUTHOR]

This article provides a detailed description of the synthesis and characterization of several compounds, specifically cis-1,3-dialkylindanes. The authors focus on the synthesis of epi-mutisianthol and epi-jungianol, two representative 1,3-dialkylindane sesquiterpenes. They successfully complete the synthesis of these compounds in six steps with high yields, demonstrating the potential for further exploration of their structure-activity relationships. The document includes data such as melting points, infrared spectra, and nuclear magnetic resonance spectra for each compound, and the supporting information is available online. [Extracted from the article]

Toward the total synthesis of natalamycin A, we have synthesized the C9-C21 segment corresponding to the northwestern part of the natural product. Key features of this synthesis were an asymmetric α-chlorination of an aldehyde using MacMillan's catalyst and stereoselective assembly of three contiguous stereocenters via a butenolide intermediate. [ABSTRACT FROM AUTHOR]

Partial oxidation of methane (CH4) to value-added products is significantly challenging due to the highly inert chemical property of CH4 at ambient conditions and easy over-oxidation into carbon dioxide (CO2) or carbon monoxide (CO) at elevated temperatures and pressures. Targeting this challenge, the efficient photocatalytic coupling of CO2 and CH4 into ethanol is demonstrated, using a cerium (Ce)-doped zinc oxide (ZnO) photocatalyst with abundant Ce--O--Zn units. Under light illumination, CO2 is adsorbed on the Ce atoms and photo-reduced to CO, and CH4 is captured by the Zn atoms and photo-oxidized to hydroperoxymethane (CH3OOH). The close proximity of Ce and Zn atoms on the Ce--O--Zn units allowed to further efficiently couple the as-formed CO and CH3OOH into ethanol. Without additional Oxygen (O2) oxidant or sacrificial regent, the ethanol production rate reached 580 µmol g-1 h-1, substantially exceeding previously reports on photocatalytic CH4 oxidation. This work features to convert two greenhouse gases into value-added chemicals with adjacent and asymmetric reaction sites, suggesting attractive potentials for CH4 and CO2 utilization. [ABSTRACT FROM AUTHOR]

Asymmetric synthesis of 3-sulfonylated 3-substituted oxindoles through the addition of sodium sulfinate salts to 3-bromo-3-substituted oxindoles has been achieved using chiral nickel complexes of N,N′-dioxides. This method facilitates the creation of diverse chiral sulfonyl oxindoles, several of which display promising anticancer properties. Notably, the catalyst demonstrates remarkable tolerance to water, crucial for maintaining enantioselectivity. Furthermore, the utilization of topographic steric maps of the catalysts offers valuable insights into the mechanism underlying enantioselection reversal. [ABSTRACT FROM AUTHOR]

Enantioselective access to polycyclic tetrahydroxanthone compounds was achieved through an organocatalyzed cascade reaction of alkene‐substituted 1,3‐diketones and alkenyloxindoles, using quinine‐derived squaramide as an efficient catalyst. It afforded a variety of optically active spirooxindole‐based tetrahydroxanthones with 18–94% yields, >19:1 dr, and 86–99% ee. [ABSTRACT FROM AUTHOR]

Dihydroquinolin‐2‐ones, recognized for their bioactive properties, feature a six‐membered structure with nitrogen‐containing heterocycles. A method has been developed for synthesizing enantioenriched 3,4‐dihydroquinoline‐2‐one derivatives. This approach utilizes an asymmetric [4+2]‐cyclization process, combining 2‐amino‐β‐nitrostyrenes with azlactones, and is facilitated by a bifunctional squaramide‐based organocatalyst. This process has enabled the creation of chiral 3,4‐dihydroquinoline‐2‐ones with complex structures, including chiral tetrasubstituted carbon stereocenters, delivering corresponding products in 26–95% yield with a diastereomeric ratio of 1.2:1–19:1 and 52–97 ee. [ABSTRACT FROM AUTHOR]

We have accomplished the first and asymmetric total synthesis of principinol B, a grayanoid possessing an oxabicyclo[3.2.1] architecture. A functionalized 5/7/6/5 tetracyclic intermediate was assembled in a convergent manner by a diastereoselective intermolecular aldol reaction and subsequent carbonyl–olefin metathesis of two enantiomerically enriched fragments. The oxabicyclo[3.2.1] architecture containing a 6,10‐ether bridge was constructed by the Williamson ether synthesis. [ABSTRACT FROM AUTHOR]