Chiral Sulfonamide Research Articles

Design of chiral acidic molecularly imprinted polymer for the enantioselective separation of (±)‐DOPA

AbstractBackgroundThe study focuses on developing a stable enantioselective matrix for the efficient chiral identification and enantioresolution of l‐DOPA and (±)‐DOPA. The matrix is derived from a copolymeric material made from poly[(vinylsulfonic acid)‐co‐(4‐vinylpyridine)] crosslinked with divinylbenzene.Resultsl‐DOPA‐vinylsulfonamide was synthesized and characterized. This chiral sulfonamide was copolymerized with 4‐vinylpyridine in the presence of a divinylbenzene crosslinker, using azobisisobutyronitrile as a thermal initiator. Post‐polymerization, the polymeric particles were treated with NaOH and subsequently washed with acid to remove the integrated l‐DOPA species. Scanning electron microscopy and Fourier transform infrared spectroscopy confirmed the imprinted l‐DOPA‐IP particles. The manufactured l‐DOPA‐IP demonstrated a tenfold greater affinity for l‐DOPA compared to d‐DOPA. Langmuir adsorption experiments at pH 6 showed a maximum capacity of 162 mg g−1. Enantiomeric excess values for l‐ and d‐DOPA, determined through optical separation using a column approach, were 94% and 82%, respectively, in the loading and recovery solutions.ConclusionThe developed copolymeric material effectively served as an enantioselective matrix, exhibiting high selectivity and capacity for l‐DOPA. The process demonstrated efficient chiral identification and separation, achieving significant enantiomeric excess values for both l‐ and d‐DOPA. © 2024 Society of Chemical Industry (SCI).

Asymmetric synthesis of allylic sulfonamides with axially and central chirality via palladium-catalyzed of atroposelective N-allylic alkylation

Axially chiral anilide compounds are an emerging but scarcely investigated class of stereogenic molecules with potential applications as chiral catalysts, biologically active scaffolds and functional materials. Compared to the C–C axially chiral molecules, the synthesis of axially chiral anilide compounds is a challenge owing to the lower rotation barriers. Herein, the construction of chiral allylic amine bearing axial chirality and central chirality via Pd-catalyzed atroposelective N-allylic alkylation reaction of cyclic vinyl carbonates and sulfonamides is reported. A diverse range of chiral sulfonamides bearing axial chirality and central chirality were synthesized in high yields and excellent enantioselectivities (up to 92 ​% yield and 99 ​% ee). In addition, the practical application of this protocol was also demonstrated by gram-scale synthesis and derivatives of the compound.

Enantioselective separation of (±)‐epinephrine by chiral acidic molecularly imprinted polymer

AbstractIn this study, we look into how poly[(4‐styrenesulfonic acid)‐co‐(4‐vinylpyridine)] crosslinked with divinylbenzene can be used as a copolymeric material to effectively recognize l‐epinephrine (L‐EP) and chirally separate (±)‐EP. It was first possible to synthesize and analyze L‐EP‐styrene‐4‐sulfonamide (L‐EP‐SSA). The resulting chiral sulfonamide was used to copolymerize with a 4‐vinylpyridine–divinylbenzene mixture. The integrated L‐EP species were removed by heating the polymer materials under strong alkaline conditions to degrade the sulfonamide links, followed by acidification in HCl solution. The imprinted L‐EP‐IP materials were analyzed using Fourier transform infrared spectroscopy and scanning electron microscopy. The produced L‐EP‐IP displayed selectivity characteristics indicative of an affinity for L‐EP almost eleven times higher than that for d‐epinephrine (D‐EP). At a pH of 7, Langmuir adsorption experiments demonstrated a maximal capacity of 165 mg g−1. Following optical separation by means of a column method, enantiomeric excess levels of L‐ and D‐EP in the initial feeding and subsequent recovering solutions were calculated to be 93% and 80%, respectively. © 2024 Society of Industrial Chemistry.

Chirality Transfer Intramolecular Pauson-Khand Reaction with N-C Axially Chiral Sulfonamides Bearing an Ene-Yne Structure.

An intramolecular Pauson-Khand reaction with enantioenriched N-C axially chiral N-allyl-N-(2-alkynylphenyl)sulfonamide derivatives proceeded with complete chirality transfer from axial chirality (P configuration) to central chirality (R configuration), affording chiral nitrogen-containing tricyclic compounds (tetrahydrocyclopentaquinolin-2-one derivatives).

Catalytic Enantioselective Synthesis of N-C Axially Chiral N-(2,6-Disubstituted-phenyl)sulfonamides through Chiral Pd-Catalyzed N-Allylation.

Recently, catalytic enantioselective syntheses of N-C axially chiral compounds have been reported by many groups. Most N-C axially chiral compounds prepared through a catalytic asymmetric reaction possess carboxamide or nitrogen-containing aromatic heterocycle skeletons. On the other hand, although N-C axially chiral sulfonamide derivatives are known, their catalytic enantioselective synthesis is relatively underexplored. We found that the reaction (Tsuji-Trost allylation) of allyl acetate with secondary sulfonamides bearing a 2-arylethynyl-6-methylphenyl group on the nitrogen atom proceeds with good enantioselectivity (up to 92% ee) in the presence of (S,S)-Trost ligand-(allyl-PdCl)2 catalyst, affording rotationally stable N-C axially chiral N-allylated sulfonamides. Furthermore, the absolute stereochemistry of the major enantiomer was determined by X-ray single crystal structural analysis and the origin of the enantioselectivity was considered.

Chiral sulfonamides with various N-heterocyclic and aromatic units – Synthesis and antiviral activity evaluation

Chiral sulfonamides with aromatic fragments are important chemical building blocks found widely in many natural products, catalysts, and molecules of biological importance. In this report, we describe the efficient synthesis of a series of chiral sulfonamides which, in addition to the aromatic part (phenyl, biphenyl, and dansyl units), possess N-heterocyclic systems. The described compounds were obtained by nucleophilic substitution of chiral N-heterocyclic amines and commercially available aromatic sulfonyl chlorides under mild conditions. All derivatives were examined in antiviral assay against AdV5, HSV-1, HPIV-3, HCMV, and EMCV viruses.

Organocatalytic atroposelective N-alkylation: divergent synthesis of axially chiral sulfonamides and biaryl amino phenols

A versatile organocatalytic atroposelective N-alkylation has been developed to access axially chiral sulfonamides bearing an allene and allyl entity, and biaryl amino phenols with high efficiency.

Discovery of new chiral sulfonamides bearing benzoxadiazole as HIF inhibitors for non-small cell lung cancer therapy: design, microwave-assisted synthesis, binding affinity,in vitroantitumoral activities andin silicostudies

Thirty-four chiral compounds having benzoxadiazole and sulfonamide moieties on the skeleton have been synthesized. The in vitro cytotoxic activity and apoptotic effects of these compounds have been evaluated using the A549 lung cancer cell line.

Palladium-Catalyzed Asymmetric Tandem Denitrogenative Heck/Tsuji–Trost of Benzotriazoles with 1,3-Dienes

The asymmetric denitrogenative cycloaddition has emerged as a powerful tool to build chiral aza-heterocyles. However, only one example of asymmetric denitrogenative cycloaddition of benzotriazole with unsaturated hydrocarbons has been explored so far, because the ring-opening of benzotriazole to generate α-imino metal carbenoid species is a thermodynamically unfavorable process. We herein report an efficient asymmetric denitrogenative cycloaddition of benzotriazoles with cyclic and acyclic 1,3-dienes enabled by Pd and chiral sulfonamide phosphine ligand. A variety of substituted hexahydrocarbazoles and indolines were delivered in good yields with high ee values. Interestingly, a pair of enantiomers could be obtained with the use of Xu1 and PC2 with the same absolute configuration. The synthetic utilities of the optically active hexahydrocarbazoles were also showcased.

Enantioselective Synthesis of Axially Chiral Sulfonamides via Atroposelective Hydroamination of Allenes

Enantioselective Synthesis of Axially Chiral Sulfonamides via Atroposelective Hydroamination of Allenes

NaClO2-mediated preparation of pyridine-2-sulfonyl chlorides and synthesis of chiral sulfonamides

A simple method to prepare azaarenesulfonyl chlorides by NaClO2-mediated oxidative chlorination of azaarenethiols have been developed, with water as the solvent. Easy purification by simple extraction and concentration gives the products in good yields. The azaarenesulfonyl chlorides readily undergo condensation with chiral amines to afford chiral sulfonamides.

Synthesis and Cytotoxic Activity of Chiral Sulfonamides Based on the 2-Azabicycloalkane Skeleton.

A series of chiral sulfonamides containing the 2-azabicycloalkane scaffold were prepared from aza-Diels–Alder cycloadducts through their conversion to amines based on 2-azanorbornane or the bridged azepane skeleton, followed by the reaction with sulfonyl chlorides. The cytotoxic activity of the obtained bicyclic derivatives was evaluated using human hepatocellular carcinoma (HCC), medulloblastoma (MB), and glioblastoma (GBM) cell lines. Chosen compounds were shown to notably reduce cell viability as compared to nonmalignant cells.

Synthesis of New Sulfonamides Based on β-Pinene

Reactions of pinane-10-sulfonyl chlorides with alkyl-, aryl-, and hetarylamines afforded up to 92% of new chiral sulfonamides that are potentially biologically active compounds.

Catalytic intramolecular hydroamination of aminoallenes using titanium and tantalum complexes of sterically encumbered chiral sulfonamides.

Catalysis using earth abundant metals is an important goal due to the relative scarcity and expense of precious metal catalysts. It would be even more beneficial to use earth abundant catalysts for the synthesis of common pharmaceutical structural motifs such as pyrrolidine and pyridine. Thus, developing titanium catalysts for asymmetric ring closing hydroamination is a valuable goal. In this work, four sterically encumbered chiral sulfonamides derived from naturally occurring amino acids were prepared. These compounds undergo protonolysis reactions with Ti(NMe2)4 or Ta(NMe2)5 to give monomeric complexes as determined by both DOSY NMR and X-ray crystallography. The resulting complexes are active for the ring closing hydroamination hepta-4,5-dienylamine to give a mixture of tetrahydropyridine and pyrrolidine products. However, the titanium complexes convert 6-methylhepta-4,5-dienylamine exclusively to 2-(2-methylpropenyl)pyrrolidine in higher enantioselectivity than those previously reported, with enantiomeric excesses ranging from 18-24%. The corresponding tantalum complexes were more selective with enantiomeric excesses ranging from 33-39%.

Chiral Nitroarenes as Enantioselective Single-Electron-Transfer Oxidants for Carbene-Catalyzed Radical Reactions.

A new class of chiral oxidants is developed. These readily accessible oxidants contain a nitro group for oxidation and a chiral sulfonamide moiety for stereoselectivity control. The chiral information from the oxidants can effectively transfer to the substrates in carbene-catalyzed β-hydroxylation of enals via single-electron-transfer radical processes. We expect these oxidants to find unique applications in other asymmetric oxidations and oxygen-atom-transferring reactions.

Practical access to axially chiral sulfonamides and biaryl amino phenols via organocatalytic atroposelective N-alkylation

The importance of axial chirality in enantioselective synthesis has been widely recognized for decades. The practical access to certain structures such as biaryl amino phenols known as NOBINs in enantiopure form, however, still remains a challenge. In drug delivery, the incorporation of axially chiral molecules in systematic screening has also received a great deal of interest in recent years, which calls for innovation and practical synthesis of structurally different axially chiral entities. Herein we present an operationally simple catalytic N-alkylation of sulfonamides using commercially available chiral amine catalysts to deliver two important classes of axially chiral compounds: structurally diverse NOBIN analogs as well as axially chiral N-aryl sulfonamides in excellent enantiopurity. Structurally related chiral sulfonamide has shown great potential in drug molecules but enantioselective synthesis of them has never been accomplished before. The practical catalytic procedures of our methods also bode well for their wide application in enantioselective synthesis.

Catalytic Enantioselective Synthesis of N-C Axially Chiral Sulfonamides through Chiral Palladium-Catalyzed N-Allylation.

In the presence of ( S,S)-Trost ligand and (allyl-Pd-Cl)2 catalyst, the reaction of allyl acetate with the anionic species prepared from various N-(2- tert-butylphenyl)sulfonamides and NaH proceeded in an enantioselective manner (up to 95% ee) to give optically active N-allylated sulfonamide derivatives possessing an N-C axially chiral structure in high yields.

Palladium-Catalyzed Asymmetric 1,4-Addition of Diarylphosphines to α,β-Unsaturated Sulfonamides

A pincer palladium-catalyzed asymmetric 1,4-addition of diarylphosphines to α,β-unsaturated sulfonamides was realized for the synthesis of chiral sulfonamide phosphines with up to 98% ee under mild conditions.

Efficient and Facile Synthesis of Chiral Sulfonamides via Asymmetric Multicomponent Reactions

Efficient and Facile Synthesis of Chiral Sulfonamides via Asymmetric Multicomponent Reactions

Synthesis of Cinchona Alkaloid Sulfonamide Polymers as Enantioselective Catalysts for the Michael Addition Reaction of β-Ketoester and Nitrostyrene

Mizoroki–Heck (MH) polymerization of cinchonidine-based sulfonamide dimers produces polymers containing a chiral sulfonamide moiety in each repeat unit. Quinidine sulfonamides are known to have excellent catalytic activity in the asymmetric Michael addition reaction of β-ketoester and nitrostyrene. We found that cinchonidine sulfonamides used as bifunctional chiral catalysts showed even higher stereoselectivity in the same reaction. The polymers synthesized by MH polymerization also showed high levels of diastereo- and enantioselectivity (up to 99% enantiomeric excess) in the reaction. Owing to the insolubility of the polymeric catalysts, they were separated easily from the reaction mixture and reused several times without any loss of catalytic activity.