Chiral Compounds Research Articles

Carbene‐Catalyzed and Pnictogen Bond‐Assisted Access to PIII‐Stereogenic Compounds

AbstractIntermolecular pnictogen bonding (PnB) catalysis has received increased interest in non‐covalent organocatalysis. It has been demonstrated that organic electron‐deficient pnictogen atoms can act as prospective Lewis acids. Here, we present a catalytic approach for the asymmetric synthesis of chiral PIII compounds by combining intramolecular PnB interactions and carbene catalysis. Our design features a pre‐chiral phosphorus molecule bearing two electron‐withdrawing benzoyl groups, resulting in the formation of a σ‐hole at the P atom. X‐ray and non‐covalent interaction (NCI) analysis indicate that the model substrates exhibit intrinsic PnB interaction between the oxygen atom of the formyl group and the phosphorus atom. This induces a conformational locking effect, leading to the crystallization of the phosphorus substrate in a preferred conformation (P212121 chiral group). Under the catalysis of N–heterocyclic carbene, the aldehyde moiety activated by the pnictogen bond selectively reacts with an alcohol to yield the corresponding chiral monoester/phosphorus product with excellent enantioselectivity. This Lewis acidic phosphorus center, aroused by the non‐polarized intramolecular pnictogen bond interaction, assists in conformational and selective regulations, providing unique opportunities for catalysis and beyond.

Chiral dinitrogen ligand enabled asymmetric Pd/norbornene cooperative catalysis toward the assembly of C–N axially chiral scaffolds

C − N axially chiral compounds have recently attracted significant interest among synthetic chemistry community due to their widespread application in pharmaceuticals, advanced materials and organic synthesis. Although the emerging asymmetric Catellani reaction offers great opportunity for their modular and efficient preparation, the only operative chiral NBE strategy to date requires using half stoichiometric amount of chiral NBE and 2,6-disubstituted bromoarenes as electrophiles. We herein report an efficient assembly of C–N axially chiral scaffolds through a distinct chiral ligand strategy. The crucial chiral source, a biimidazoline (BiIM) chiral dinitrogen ligand, is used in relatively low loading and permits the use of less bulky bromoarenes. The method also features the use of feedstock plain NBE, high reactivity, good enantioselectivity, ease of operation and scale-up. Applications in the preparation of chiral optoelectronic material candidates featuring two C–N chiral axes and a chiral ligand for asymmetric C–H activation have also been demonstrated.

Investigation of infra-red spectra of three chiral liquid crystalline compounds with different fluorosubstitution of benzene ring

The IR spectra of three liquid crystalline compounds, differing only by the number of fluorine atoms in the molecular core, are investigated. The DFT+D3/BLYP-def2SVP calculations for isolated molecules are applied for the band assignments of the experimental IR spectra collected in the crystal phase. Additional DFT calculations, including the B3LYP exchange-correlation functional and def2TZVPP basis set, are also performed for the compound without the fluorine atoms in the molecular core. The scaling factors between the experimental and calculated peak positions, obtained at different levels of theory, are compared. For all compounds, the absorption bands assigned to the C=O stretching vibrations are analyzed as a function of temperature in the isotropic liquid, smectic phases, and crystal phase. The formation of hydrogen bonding involving the C=O groups during crystallization is inferred. The differences in the crystallization temperature of three compounds and the presence of the hexatic smectic phase for only one compound are discussed.

Bragg diffraction of higher orders on oblique helicoidal liquid crystal structures

ABSTRACT For the oblique helicoidal (ChOH) structure of the chiral twist-bend nematic-forming mixture of CB7CB/CB6OCB/5CB doped by light-sensitive chiral compound based on azo-fragment, at oblique incidence of light two consequent states of Bragg reflection in the visible spectral range from 400 to 750 nm were experimentally observed in the course of decreasing the applied electric field. These states were assigned to different orders of Bragg’s diffraction occurring at ChOH layers with full pitch periodicity P. While the second and third orders of Bragg’s diffraction can be easily observed in conditions of standard electrooptic cell, the first order could be revealed only at very high electric field near the ‘red’ edge of the visible spectral range. For the second and third orders of diffraction there is a narrow range of electric field where both diffraction orders are observed (so-called hybrid state), with transmittance spectra of the ChOH structure showing two peaks at the short-wavelength and the long-wavelength edges of the visible spectral range. Model calculations of Bragg’s reflection of light were carried out using literature values of elasticity constants and dielectric permittivity, and the calculated plots of the selective reflection maximum vs. voltage were in good agreement with experimental data.

Photochemical Synthesis of Chiral Heterocycles via Asymmetric Carbon‐Heteroatom Bond Formation

AbstractChiral heterocyclic compounds play a crucial role in the pharmaceutical science, materials science, and agrochemical industries. The critical step for synthesizing chiral heterocycles is the formation of asymmetric carbon‐heteroatom bonds, which can be achieved in a chiral environment under thermal or photochemical conditions. However, photochemical asymmetric transformation has become an area of immense growth in the past 15 years. In the drug discovery and development era, chiral photochemical transformations have drawn the attention of researchers to develop new synthetic strategies for chiral heterocycles via asymmetric carbon‐heteroatom bond formation. Chiral photochemistry in the pathway of asymmetric synthesis requires a chirality source which is transferred to the products. A catalytic chiral metal complexing agent or a chiral photosensitizer that generally follows a single electron transfer (SET) or oxidative and reductive quenching cycle has been widely exploited to achieve this goal. In this review, we have demonstrated the recent development of photochemical synthesis of chiral heterocycles via asymmetric carbon‐heteroatom bond formation by using a chiral metal catalyst, asymmetric organocatalyst, or dual catalytic system based on their plausible mechanism.

New Essential Oils from Ecuadorian Gynoxys cuicochensis Cuatrec. and Gynoxys sancti-antonii Cuatrec. Chemical Compositions and Enantioselective Analyses.

The present study belonged to an unfunded project, dealing on the systematic description of unprecedented essential oils (EOs), distilled from 12 species of genus Gynoxys Cuatrec. In this very case, the aim was the first chemical and enantiomeric analyses of two volatile fractions, obtained from the leaves of Gynoxys cuicochensis Cuatrec. and Gynoxys sancti-antonii Cuatrec. These EOs were analyzed by GC-MS (qualitatively) and GC-FID (quantitatively), detecting 89 and 60 components from G. cuicochensis and G. sancti-antonii, respectively. Major components for G. cuicochensis EO, on a nonpolar and polar stationary phase, were α-pinene (29.4-29.6%), p-vinylguaiacol (3.3-3.6%), and germacrene D (20.8-19.9%). In G. sancti-antonii EO, the main compounds were α-pinene (3.0-2.9%), β-pinene (12.9-12.1%), γ-curcumene (19.7-18.3%), germacrene D (9.0% on the polar phase), ar-curcumene (5.3% on the polar phase), δ-cadinene (4.1-4.6%), α-muurolol (3.3-2.4%), α-cadinol (3.0% on both columns), and an undetermined compound, of molecular weight 220. In addition to chemical composition, the enantioselective analysis of the main chiral compounds was carried out on two different chiral selectors. In G. cuicochensis EO, (1R,5R)-(+)-α-pinene, (S)-(+)-β-phellandrene, (R)-(-)-piperitone, and (S)-(-)-germacrene D were enantiomerically pure, whereas β-pinene, sabinene, α-phellandrene, limonene, linalool, and terpinen-4-ol were observed as scalemic mixtures. On the other hand, in G. sancti-antonii EO, the pure enantiomers were (1S,5S)-(-)-α-pinene, (1R,5R)-(+)-sabinene, (R)-(-)-β-phellandrene, (S)-(-)-limonene, (1S,2R,6R,7R,8R)-(+)-α-copaene, (R)-(-)-terpinen-4-ol, and (S)-(-)-germacrene D, whereas β-pinene, linalool, and α-terpineol were present as scalemic mixtures. The principal component analysis demonstrated that G. cuicochensis volatile fraction was quite similar to many of the other EOs of the same genus, whereas G. sancti-antonii produced the most dissimilar EO. Furthermore, the enantioselective analyses showed the usual variable enantiomeric distribution, with a greater presence of enantiomerically pure compounds in G. sancti-antonii EO.

Synthesis and Characterization of a Cyclic Trimer of a Chiral Spirosilabifluorene.

A chiral shape-persistent macrocyclic compound (Si-[3]), designed by the C/Si substitution in the spiro-atom of spirobifluorene in the cyclic trimer (C-[3]), has been successfully synthesized in this study. The C/Si substitution made the spiro-conjugation and energy levels of HOMO and LUMO decrease. Due to the silicon substitution, the macrocyclic compound Si-[3] was able to be degraded by fluoride ions, but its reaction rate was slower than that of the unsubstituted spirosilabifluorene, showing the chemical stability of Si-[3]. Furthermore, the chiroptical properties of Si-[3] with D3-symmetric macrocyclic structure were investigated, and (P,P,P)-Si-[3] showed a high emission quantum yield (Φf=80 %) and moderate dissymmetry factor of circularly polarized luminescence (CPL) (glum,exp=-1.2×10-3). According to the time-dependent density-functional theory (TD-DFT) calculations using polarizable continuum model (PCM), the bright CPL from Si-[3] was explained by a planarization of one bisilafluorenyl moiety at the excited state, which is responsible for the almost fully-allowed radiative transition with a short emission lifetime of τf=1.89 ns.

An enantioselective fluorescent probe for detecting arginine and glutamic acids

Amino acids are important chiral compounds in the human body, and are important basic components that make up the human body and play an important role in the human body. Among them, different enantiomers of an amino acid may have different roles, and different types of amino acids can be interconverted. However, the content of D-amino acids is much lower than that of L-amino acids, which is difficult to be detected. At present, many of the potential roles of D-amino acids, such as the conversion of D-amino acids to each other, have not yet been fully revealed. Hence, we synthesized fluorescent probe (R)-5 by condensation of 1,1’-Bi-2-naphthol (BINOL) and 2-(Aminomethyl)pyridine with Schiff base, which can recognize both D-arginine and D-glutamic acid at low concentrations. Meanwhile, (R)-5 can be applied to paper-based sensors for the detection of arginine and glutamate in living cells and for food amino acid detection.

Application of Lipases for Obtaining Optically Active Organic Compounds

Among the diversity of biotechnological processes that are used in the chemical industry, particular attention is drawn to the production of chiral compounds, both as the target and intermediate products in the synthesis of drugs. This review highlights recent advances in the use of lipases for the production of optically active organic compounds.

Preparation and sensing performance of chiral carbon Dot@MOF electrode material

Abstract Chirality is a ubiquitous phenomenon in nature. The identification of chiral compounds has important theoretical significance and application prospects in many fields such as biology, medicine, and food. This paper proposes an innovative approach to differentiate enantiomers by using the synergistic effect of chiral MOFs and CDs through electrochemiluminescence. The results demonstrate that CDs@[Zn(D-cam)(phen)(H2O)]n exhibit higher electrochemiluminescent response towards L/D-Trp, enabling the detection of Trp enantiomers. This research suggests that selective recognition of amino acid enantiomers can be achieved through ECL-based nanocomposites of CDs and porous MOFs.

Atroposelective synthesis of biaxial bridged eight-membered terphenyls via a Co/SPDO-catalyzed aerobic oxidative coupling/desymmetrization of phenols

Bridged chiral biaryls are axially chiral compounds with a medium-sized ring connecting the two arenes. Compared with plentiful methods for the enantioselective synthesis of biaryl compounds, synthetic approaches for this subclass of bridged atropisomers are limited. Here we show an atroposelective synthesis of 1,3-diaxial bridged eight-membered terphenyl atropisomers through an Co/SPDO (spirocyclic pyrrolidine oxazoline)-catalyzed aerobic oxidative coupling/desymmetrization reaction of prochiral phenols. This catalytic desymmetric process is enabled by combination of an earth-abundant Co(OAc)2 and a unique SPDO ligand in the presence of DABCO (1,4-diaza[2.2.2]bicyclooctane). An array of diaxial bridged terphenyls embedded in an azocane can be accessed in high yields (up to 99%) with excellent enantio- (>99% ee) and diastereoselectivities (>20:1 dr).

Sunlight-Driven Smart Windows with a Wide Temperature Range of Optical Switching Based on Chiral Nematic Liquid Crystals.

Photoresponsive liquid crystals are promising materials for sunlight-driven smart windows, which can automatically change their optical states in response to sunlight and control energy flow between the inside and outside of a building. Herein, liquid-crystalline systems are developed that show a transparent-scattering transition upon irradiation with sunlight in a wide temperature range. Push-pull azobenzenes with axial chirality have been newly developed as photochromic chiral dopants to allow changes in mesostructures of liquid crystals in response to sunlight. To realize optical switching, photochromic and photoinert chiral compounds with opposite handedness of helical twisting are doped in liquid crystals. This liquid crystalline sample with a compensated nematic phase is transparent in its initial state. Upon irradiation with sunlight, this sample transforms to a scattering state due to the formation of helical mesostructures along with photoisomerization of azobenzene moieties and the change in the helical twisting power. After the cease of irradiation, the sample reverts to the transparent state through thermal back isomerization of azobenzene moieties. This system significantly improves the operating temperature range of sunlight-driven smart windows based on liquid crystals: the transparent-scattering transition is observed at 4-42 °C. The present mechanism allows development of autonomous and wireless smart windows adaptable to various environments.

Metal‐Catalyzed Enantioselective Cleavage of Aromatic C−O Bonds

AbstractPhenol derivatives are naturally abundant or can be easily fabricated from commercially accessible building blocks. In recent years, with the aim of producing functionally important chiral compounds in enantioenriched form, there has been initial progress in the development of metal‐catalyzed cross‐coupling reactions that involve the enantioselective cleavage of aromatic C−O bonds. This concept encompasses a review of the significant advancements in this field, as well as the associated strategies. Moreover, the challenges and potential opportunities in this area are also underscored.

Organometallic Chirality Sensing via "Click"-Like η6-Arene Coordination with an Achiral Cp*Ru(II) Piano Stool Complex.

Piano stool complexes have been studied over many years and found widespread applications in organic synthesis, catalysis, materials and drug development. We now report the first examples of quantitative chiroptical molecular recognition of chiral compounds through click-like η6-arene coordination with readily available half sandwich complexes. This conceptually new approach to chirality sensing is based on irreversible acetonitrile displacement of [Cp*Ru(CH3CN)3]PF6 by an aromatic target molecule, a process that is fast and complete within a few minutes at room temperature. The metal coordination coincides with characteristic circular dichroism inductions that can be easily correlated to the absolute configuration and enantiomeric ratio of the bound molecule. A relay assay that decouples the determination of the enantiomeric composition and of the total sample amount by a practical CD/UV measurement protocol was developed and successfully tested. The introduction of piano stool complexes to the chiroptical sensing realm is mechanistically unique and extends the scope of currently known methods with small-molecule probes that require the presence of amino, alcohol, carboxylate or other privileged functional groups for binding of the target compound. A broad application range including pharmaceutically relevant multifunctional molecules and the use in chromatography-free asymmetric reaction analysis are also demonstrated.

Organometallic Chirality Sensing via “Click”‐Like η6‐Arene Coordination with an Achiral Cp*Ru(II) Piano Stool Complex

AbstractPiano stool complexes have been studied over many years and found widespread applications in organic synthesis, catalysis, materials and drug development. We now report the first examples of quantitative chiroptical molecular recognition of chiral compounds through click‐like η6‐arene coordination with readily available half sandwich complexes. This conceptually new approach to chirality sensing is based on irreversible acetonitrile displacement of [Cp*Ru(CH3CN)3]PF6 by an aromatic target molecule, a process that is fast and complete within a few minutes at room temperature. The metal coordination coincides with characteristic circular dichroism inductions that can be easily correlated to the absolute configuration and enantiomeric ratio of the bound molecule. A relay assay that decouples the determination of the enantiomeric composition and of the total sample amount by a practical CD/UV measurement protocol was developed and successfully tested. The introduction of piano stool complexes to the chiroptical sensing realm is mechanistically unique and extends the scope of currently known methods with small‐molecule probes that require the presence of amino, alcohol, carboxylate or other privileged functional groups for binding of the target compound. A broad application range including pharmaceutically relevant multifunctional molecules and the use in chromatography‐free asymmetric reaction analysis are also demonstrated.

Structural Regulations of Layered Borates: From Centric Layers to Chiral Porous Layers.

Three pentaborates were made by precise structural regulations under hydrothermal conditions, namely, K2Cs[B5O8(OH)]·0.5CO3 (1), KNa4Cs[B5O8(OH)]2·2OH (2), and NaBa[B5O8.5(OH)] (3). Compound 1 features the typical 2D layers constructed from the four-connected B5O10(OH) clusters. By adjustment of the reactants and pH values of the systems to remove interlayered CO3 2- groups, the centric layers in 1 were transformed to the chiral layers of 2. By further adjusting cationic templates based on host-guest charge matching, the B5O10(OH) cluster unit was transformed to B5O11(OH), which built the chiral porous layers of 3. The chiral compounds 2 and 3 exhibit moderate second harmonic generation (SHG) responses of 1.1 and 1.7 times that of KDP (KH2PO4). The structural regulations actualize the evolutions on both structural symmetries and dimensions.

Enantioselectivity regulation of antibody against chiral herbicide metolachlor based on interaction at chiral center

Enantioselective antibodies have emerged as great potential biomaterials in the fields of immunoassays and chiral separation. However, cross-reactivity of antibodies to the distomer may severely restrict the application. Comprehending the interaction mechanism between antibodies and enantiomers could be beneficial to produce superior enantioselective antibodies. In this study, a pair of recombinant antibodies (RAbs) against metolachlor enantiomers at chiral carbon (αSS-MET and αSR-MET) were generated and characterized. The αSS-MET-RAb and αSR-MET-RAb showed comparable sensitivity and specificity to the parental monoclonal antibodies by icELISA, with IC50 values of 3.45 and 223.77 ng/mL, respectively. Moreover, the complex structures of RAbs and corresponding eutomer were constructed and analyzed, and site-specific mutagenesis was utilized to verify the reliability of the enantioselective mechanism elucidated. It demonstrated that the strength of the interaction between the chiral center region of eutomer and the antibody was the key factor for the enantioselectivity of antibody. Increasing this interaction could limit the conformational adjustment of the distomer in a specific chiral recognition cavity, thus decreasing the affinity of the antibody to the distomer. This work provided the in-depth analysis of enantioselective mechanism for two RAbs and paved the way to regulate antibody enantioselective performance for immunoassays of chiral compounds.

Chemical imitation of yeast fermentation by the drosophilid-pollinated deceptive trap-flower Aristolochia baetica (Aristolochiaceae)

Deceptive flowers, unlike in mutualistic pollination systems, mislead their pollinators by advertising rewards which ultimately are not provided. Although our understanding of deceptive pollination systems increased in recent years, the attractive signals and deceptive strategies in the majority of species remain unknown. This is also true for the genus Aristolochia, famous for its deceptive and fly-pollinated trap flowers. Representatives of this genus were generally assumed to be oviposition-site mimics, imitating vertebrate carrion or mushrooms. However, recent studies found a broader spectrum of strategies, including kleptomyiophily and imitation of invertebrate carrion. A different deceptive strategy is presented here for the western Mediterranean Aristolochia baetica L. We found that this species is mostly pollinated by drosophilid flies (Drosophilidae, mostly Drosophila spp.), which typically feed on fermenting fruit infested by yeasts. The flowers of A. baetica emitted mostly typical yeast volatiles, predominantly the aliphatic compounds acetoin and 2,3-butandiol, and derived acetates, as well as the aromatic compound 2-phenylethanol. Analyses of the absolute configurations of the chiral volatiles revealed weakly (acetoin, 2,3-butanediol) to strongly (mono- and diacetates) biased stereoisomer-ratios. Electrophysiological (GC-EAD) experiments and lab bioassays demonstrated that most of the floral volatiles, although not all stereoisomers of chiral compounds, were physiologically active and attractive in drosophilid pollinators; a synthetic mixture thereof successfully attracted them in field and lab bioassays. We conclude that A. baetica chemically mimics yeast fermentation to deceive its pollinators. This deceptive strategy (scent chemistry, pollinators, trapping function) is also known from more distantly related plants, such as Arum palaestinum Boiss. (Araceae) and Ceropegia spp. (Apocynaceae), suggesting convergent evolution. In contrast to other studies working on floral scents in plants imitating breeding sites, the present study considered the absolute configuration of chiral compounds.

Synthesis of Planar Chiral Compounds Containing α-Amino Phosphonates for Antiplant Virus Applications against Potato Virus Y.

An unprecedented study of the application of planar chiral compounds in antiviral pesticide development is reported. A class of multifunctional planar chiral ferrocene derivatives bearing α-amino phosphonate moieties was synthesized. These compounds, exhibiting superior optical purities, were subsequently subjected to antiviral evaluations against the notable plant pathogen potato virus Y (PVY). The influence of the absolute configurations of the planar chiral compounds on their antiviral bioactivities was significant. A number of these enantiomerically enriched planar chiral molecules demonstrated superior anti-PVY activities. Specifically, compound (Sp, R)-9n displayed extraordinary curative activities against PVY, with a 50% maximal effective concentration (EC50) of 216.11 μg/mL, surpassing the efficacy of ningnanmycin (NNM, 272.74 μg/mL). The protective activities of compound (Sp, R)-9n had an EC50 value of 152.78 μg/mL, which was better than that of NNM (413.22 μg/mL). The molecular docking and defense enzyme activity tests were carried out using the planar chiral molecules bearing different absolute configurations to investigate the mechanism of their antiviral activities against PVY. (Sp, R)-9n, (Sp, R)-9o, and NMM all showed stronger affinities to the PVY-CP than the (Rp, S)-9n. Investigations into the mechanisms revealed that the planar chiral configurations of the compounds played pivotal roles in the interactions between the PVY-CP molecules and could augment the activities of the defense enzymes. This study contributes substantial insights into the role of planar chirality in defending plants against viral infections.

Carbene-Catalyzed Atroposelective Construction of Chiral Diaryl Ethers.

Atropoisomeric chemotypes of diaryl ethers-related scaffolds are prevalent in naturally active compounds. Nevertheless, there remains considerable research to be carried out on the catalytic asymmetric synthesis of these axially chiral molecules. In this instance, we disclose an N-heterocyclic carbene (NHC)-catalyzed synthesis of axially chiral diaryl ethers via atroposelective esterification of dialdehyde-containing diaryl ethers. NHC desymmetrization produces axially chiral diaryl ether atropisomers with high yields and enantioselectivities in moderate circumstances. Chiral diaryl ether compounds may be precursors for highly functionalized diaryl ethers with bioactivity and chiral ligands for asymmetric catalysis.