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The worldwide increase in cognitive decline, both in aging and with psychiatric disorders, warrants a search for pharmacological treatment. Although dopaminergic treatment approaches represent a major step forward, current dopamine transporter (DAT) inhibitors are not sufficiently specific as they also target other transporters and receptors, thus showing unwanted side effects. Herein, we describe an enantiomerically pure, highly specific DAT inhibitor, S-CE-123, synthetized in our laboratory. Following binding studies to DAT, NET and SERT, GPCR and kinome screening, pharmacokinetics and a basic neurotoxic screen, S-CE-123 was tested for its potential to enhance and/or rescue cognitive functions in young and in aged rats in the non-invasive reward-motivated paradigm of a hole-board test for spatial learning. In addition, an open field study with young rats was carried out. We demonstrated that S-CE-123 is a low-affinity but highly selective dopamine reuptake inhibitor with good bioavailability. S-CE-123 did not induce hyperlocomotion or anxiogenic or stereotypic behaviour in young rats. Our compound improved the performance of aged but not young rats in a reward-motivated task. The well-described impairment of the dopaminergic system in aging may underlie the age-specific effect. We propose S-CE-123 as a possible candidate for developing a tentative therapeutic strategy for age-related cognitive decline and cognitive dysfunction in psychiatric disorders. [ABSTRACT FROM AUTHOR]

Chirality plays a vital role in the lives of humans, plants, and animals because various proteins, amino acids, hormones, enzymes are chiral in nature. It is important in different areas such as agriculture, medicine, food, and chemical industries. Chiral compounds may have varying pharmacodynamic and pharmacokinetic parameters, as well as pharmacological and toxic characteristics. Because of their advantages in terms of potency and safety, enantiomerically pure chiral compounds are increasingly being developed by the pharmaceutical industry. This is reinforced by the development of novel methods for enantioselective chiral chemical synthesis as well as the ability of enantioselective analytical methods to identify and quantify small enantiomeric impurities in the presence of a significant excess of another enantiomer. This work aims to offer a short overview on the essential principle of chiral separations on a quantitative scale through this article. In addition, this article includes various types of chiral stationary phases and their applications. Furthermore, gas and liquid chromatography are also discussed as analytical methods used for the separation of chiral compounds. [ABSTRACT FROM AUTHOR]

Racemic 1-(adamantan-1-yl)propane-1,2-diamine was synthesized from trans-2-(adamantan-1-yl)-3-methylaziridine, and its optical resolution was achieved with the use of L-malic acid. The isolated (1S,2R)-stereoisomer was derivatized with benzil, and enantiomeric purity of the resulting (2S,3R)-2-(adaman-tan-1-yl)-3-methyl-5,6-diphenyl-2,3-dihydropyrazine was determined by chiral HPLC. The reaction of (1S,2R)-1-(adamantan-1-yl)propane-1,2-diamine with carbon disulfide gave (4S,5R)-4-(adamantan-1-yl)-5-methylimidazolidine-2-thione whose absolute configuration was established by X-ray analysis. Racemic and optically pure (1S,2R)-1-(adamantan-1-yl)propane-1,2-diamines were used to obtain ligands and their metal complexes, and the latter were studied as catalysts in model epoxidation, Michael, and Henry reactions. Enantiodivergence was observed in the Henry reaction catalyzed by structurally related ligands. [ABSTRACT FROM AUTHOR]

The research progress of chemical resolution in recent years is reviewed, and the research progress of classical salt formation resolution, inclusion resolution and combination resolution are emphatically analyzed, as well as the advantages and disadvantages of each resolution, and finally summarizes and prospects the chemical resolution method.In the future, with the demand of high purity production of high-end chemicals, the optical purity requirements for chiral compounds will be higher and higher.Due to its advantages of simple operation, low cost and easy mass production, chemical resolution is widely used in the separation of enantiomers, and will play an important and irreplaceable role in chiral resolution. [ABSTRACT FROM AUTHOR]

Tetrahydroisoquinoline alkaloids (THIQAs) are ubiquitous compounds with important pharmaceutical and biological activity. Their key N-heterocyclic structural motifs are synthesised via Pictet–Spengler (P–S) reaction by norcoclaurine synthases (NCS) in plants. The synthesis of 1-aryl-tetrahydroisoquinoline alkaloids has attracted increasing attention due to their antitumor and antivirus activities. Herein, the L68T/M97V mutant of NCS from Thalictrum flavum with improved activity was developed by semi-rational design. This mutant not only showed higher catalytic performance (> 96% conversion) toward benzaldehyde and dopamine over the wild-type enzyme, but also catalysed the P–S reaction of the bulky substrate 4-biphenylaldehyde and dopamine with high conversion (> 99%) for the effective synthesis of 1-aryl-THIQA. In terms of stereoselectivity, all products synthesised by the L68T/M97V mutant showed high optical purity (92–99% enantiomeric excess). [ABSTRACT FROM AUTHOR]

Vildagliptin (VIL) is a dipeptidyl peptidase-4 inhibitor used in the treatment of type 2 diabetes mellitus; in therapy, it is available as the enantiomerically pure S-VIL, the other enantiomer R-VIL being considered as an enantiomeric impurity. A systematic screening of 16 cyclodextrin (CD) derivatives as chiral selectors was performed at three pH levels using phosphate (pH 2.5, pH 7.0) and acetate (pH 4.5) buffers. Method optimization employed an experimental design approach, systematically investigating the effect of buffer and CD concentration, buffer pH, capillary temperature, and applied voltage on the chiral resolution and analysis time. The method’s analytical performance was thoroughly assessed and subsequently employed for determining the enantiomeric purity of VIL in a pharmaceutical formulation. The properties of the inclusion complexes, such as stoichiometry and atomic level intermolecular host–guest interactions were studied by NMR measurements and molecular modeling. Native α-CD at acidic pH has demonstrated its exceptional suitability for the separation of VIL enantiomers with a favorable migration order (R-VIL followed by S-VIL). The optimized analytical conditions (75 mM acetate buffer, pH 4.5, containing 50 mM α-CD, 18 kV applied voltage, and 15 °C capillary temperature) provided a baseline separation of VIL enantiomers within 9 min. The developed method represents a cost-effective alternative to the enantiomeric impurity control of VIL. Symmetry is often a fundamental aspect of molecular structures and interactions, and our detailed analysis of the chiral recognition process contributes to the understanding of symmetry-related aspects in molecular systems. This developed method not only offers a cost-effective alternative for the enantiomeric impurity control of VIL but also provides valuable information regarding the mechanism of the chiral recognition process, aligning with the broader themes of symmetry in molecular sciences.

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At different reaction temperatures, using Cu(NO3)2·3H2O to react with enantiomerically pure N-donor ligands (LS/LR), respectively, two pairs of chiral one-dimensional (1D) CuII chain enantiomers formulated as [Cu(μ2-NO3)(NO3)(LS)]n/[Cu(μ2-NO3)(NO3)(LR)]n (S-1-Cu / R-1-Cu , formed at 40 °C with an NO3− group as a sole bridging ligand) and [Cu(μ2-LS)(NO3)2]n/[Cu(μ2-LR)(NO3)2]n (S-2-Cu / R-2-Cu , formed at 25 °C with LS or LR as a bridging ligand) were prepared, where LS/LR = (+)/(−)-4,5-pinenepyridyl-2-pyrazine. Interestingly, such a disparity in bridging ligands leads not only to their distinct structural features but also to their completely different magnetic couplings together with a large difference in their nonlinear optical responses. S-1-Cu with a 1D helical structure shows weak ferromagnetic coupling between CuII ions, while S-2-Cu with a 1D stairway-like structure presents weak antiferromagnetic coupling. In particular, they simultaneously possess both second- and third-harmonic generation (SHG and THG) responses in one molecule with large strength differences. More remarkably, S-1-Cu exhibits a very large THG response (162 × α-SiO2), which is 22.5 times that of S-2-Cu , and the SHG strength of S-1-Cu is more than 3 times that of S-2-Cu. This work demonstrates that reaction temperature has a great impact on the self-assembled structures of coordination polymers and subsequently results in their large performance differences. [ABSTRACT FROM AUTHOR]

17O NMR spectroscopy is a powerful technique, which can provide unique information regarding the structure and reactivity of biomolecules. However, the low natural abundance of 17O (0.04 %) generally requires working with enriched samples, which are not easily accessible. Here, we present simple, fast and cost‐efficient 17O‐enrichment strategies for amino acids and peptides by using mechanochemistry. First, five unprotected amino acids were enriched under ambient conditions, consuming only microliter amounts of costly labeled water, and producing pure molecules with enrichment levels up to ∼40 %, yields ∼60‐85 %, and no loss of optical purity. Subsequently, 17O‐enriched Fmoc/tBu‐protected amino acids were produced on a 1 g/day scale with high enrichment levels. Lastly, a site‐selective 17O‐labeling of carboxylic functions in peptide side‐chains was achieved for RGD and GRGDS peptides, with ∼28 % enrichment level. For all molecules, 17O ssNMR spectra were recorded at 14.1 T in reasonable times, making this an important step forward for future NMR studies of biomolecules. [ABSTRACT FROM AUTHOR]

A focused library of 1-adamantyl arylthiophosphonates was prepared in racemic form. An enantioseparation method was developed for P-stereogenic thiophosphonates using (S)-1-phenylethylamine as the resolving agent. Under optimized conditions, three out of the five arylthiophosphonates were prepared in enantiopure form (ee > 99%). The subsequent desulfurization of optically active arylthiophosphonates gave the corresponding H-phosphinates without significant erosion of enantiomeric purity (ee = 95–98%). Hence, this reaction sequence can be considered an alternative method for the preparation of 1-adamantyl aryl-H-phopshinates. The absolute configuration of the (S)-1-adamantyl phenylphosphonothioic acid was assigned using single-crystal XRD and it allowed the confirmation that the removal of the P = S group proceeds with retention of configuration. The organocatalytic applicability of (S)-1-adamantyl phenylphosphonothioic acid was also evaluated as a P-stereogenic Brønsted acid. [ABSTRACT FROM AUTHOR]

Poly(lactide) (PLA) and poly(ethylene glycol) (PEG)-based hydrogels were prepared by mixing phosphate buffer saline (PBS, pH 7.4) solutions of four-arm (PEG-PLA)2-R-(PLA-PEG)2 enantiomerically pure copolymers having the opposite chirality of the poly(lactide) blocks. Dynamic Light Scattering, rheology measurements, and fluorescence spectroscopy suggested that, depending on the nature of the linker R, the gelation process followed rather different mechanisms. In all cases, mixing of equimolar amounts of the enantiomeric copolymers led to micellar aggregates with a stereocomplexed PLA core and a hydrophilic PEG corona. Yet, when R was an aliphatic heptamethylene unit, temperature-dependent reversible gelation was mainly induced by entanglements of PEG chains at concentrations higher than 5 wt.%. When R was a linker containing cationic amine groups, thermo-irreversible hydrogels were promptly generated at concentrations higher than 20 wt.%. In the latter case, stereocomplexation of the PLA blocks randomly distributed in micellar aggregates is proposed as the major determinant of the gelation process. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: NiH‐catalyzed multicomponent reductive hydrofunctionalization of alkenes is an attractive but poorly explored approach to rapidly increasing molecular complexity. In this process, the selective generation of the desired product can be challenging. Herein, we report that a highly chemo‐, regio‐ and enantioselective reductive hydrocarbonylation of alkenes has been achieved using a chloroformate ester as a source of CO. A wide range of structurally diverse α‐hydroxy ketones, privileged structural elements in bioactive molecules and useful building blocks, were obtained from such reactions with high enantiomeric purity. [ABSTRACT FROM AUTHOR]

MDMA (3,4-methylenedioxymethamphetamine) is a chiral psychoactive recreational drug sold in illicit markets as racemate. Studies on the impact of MDMA on aquatic organisms are scarce. While enantioselectivity in toxicity in animals and humans has been reported, none is reported on aquatic organisms. This study aimed to investigate the ecotoxicological effects of MDMA and its enantiomers in Daphnia magna. For that, enantiomers (enantiomeric purity > 97%) were separated by liquid chromatography using a homemade semipreparative chiral column. Daphnids were exposed to three concentrations of (R,S)-MDMA (0.1, 1.0 and 10.0 µg L−1) and two concentrations of (R)- and (S)-enantiomers (0.1 and 1.0 µg L−1) over the course of 8 days. Morphophysiological responses were dependent on the substance form and daphnia development stage, and they were overall not affected by the (R)-enantiomer. Changes in swimming behaviour were observed for both the racemate and its enantiomers, but enantioselective effects were not observed. Reproductive or biochemical changes were not observed for enantiomers whereas a significant decrease in acetylcholinesterase and catalase activity was noted at the highest concentration of (R,S)-MDMA (10 µg L−1). Overall, this study showed that sub-chronic exposure to MDMA racemate and its enantiomers can interfere with morphophysiological and swimming behaviour of D. magna. In general, the (R)-enantiomer demonstrated less toxicity than the (S)-enantiomer. [ABSTRACT FROM AUTHOR]

Chiral amines are essential components for many pharmaceuticals and agrochemicals. However, the difficulty in obtaining enantiomerically pure amines limits their application. In this study, hollow amorphous ZIF-90 (HamZIF-90) materials were prepared by template engraving, and chemical–enzyme coupling catalysts (HamZIF-90@Pd@CALB) were constructed for the chiral resolution of 1-phenylethylamine. Different from conventional materials, HamZIF-90 had tunable hollow structures by altering its central node zinc ion concentrations, and the embedded hydrogel template gave it more pore structures, which facilitated the loading of enzyme molecules and Pd nanoparticles (NPs). The establishment of the coupling catalysts shortened the mass transfer distance of the reactant molecules between the metal nanoparticles and the enzyme catalyst in the dynamic kinetic resolution (DKR) reaction, resulting in 98% conversion of 1-phenylethylamine and 93% selectivity of Sel.R-amide. The proposal of this idea provided a good idea for future tailor-made MOFs loaded with chemical and enzyme coupled catalyst. [ABSTRACT FROM AUTHOR]

The enantiomerically pure ligand BisNap-Phos was obtained in a straightforward sequence of reactions beginning with inexpensive starting materials under the readily affordable conditions in high overall yield. An asymmetric BisNap-Phos-palladium complex-catalyzed Suzuki–Miyaura coupling leading to axially chiral biaryl compounds was described. The reactions were carried out under mild conditions in aqueous and organic media. A series of atropisomeric biaryls were synthesized with excellent yields and high enantioselectivities (up to 86% ee). The methodology provides an efficient and practical strategy for the synthesis of novel multifunctionalized axially chiral biaryl compounds under mild environmentally friendly and easily affordable conditions. [ABSTRACT FROM AUTHOR]

Kinetic resolution is one of the methods which allows obtaining enantiomerically pure compounds. In the study presented herein, enantioselective biotransformations of (R,S)-1-phenylethanol were performed with the use of various catalytic systems containing ionic liquids and n-heptane or toluene as a reaction medium, vinyl acetate or isopropenyl acetate as an acetylating agent, and lipases from Burkholderia cepacia or Candida rugosa. The conducted studies proved that the use of Burkholderia cepacia lipase, vinyl acetate, and n-heptane with [EMIM][BF4] allows obtaining enantiomerically pure 1-phenylethyl acetate, with the enantiomeric excess of products eep = 98.9%, conversion c = 40.1%, and high value of enantioselectivity E > 200. Additionally, the use of ionic liquids allowed us to reuse enzyme in 5 reaction cycles, ensuring the high operational stability of the protein. [ABSTRACT FROM AUTHOR]

Morpholine is a heterocyclic moiety that is widely used in medicinal chemistry as a building block. It has unique physicochemical properties, as it can improve both pharmacokinetic and pharmacodynamic properties of active pharmaceutical ingredients. However, the efficient synthesis of enantiomerically pure morpholine building blocks remains challenging. Herein, we report the synthesis of optically pure 3-hydroxymethylmorpholine building blocks, as well as their sulfamidates, exploiting a stereospecific strategy from chiral pool material. [ABSTRACT FROM AUTHOR]

In this study, wheat straw was fractionated into carbohydrates (cellulose and hemicellulose) by ammonia–mechanical pretreatment for l-lactic acid fermentation. Under optimal conditions (aqueous ammonia concentration: 19% w/w, liquid–solid ratio: 2.1:1 w/w, holding time: 4.80 h), the delignification was more than 60%. After enzymatic hydrolysis, the maximum conversions of cellulose and hemicellulose were 92.5% and 83.4% based on the pretreatment residue, respectively. The wheat straw hydrolysate was used to produce l-lactic acid with Thermoanaerobacter sp. DH-217G, which obtained a yield of 88.6% and an optical purity of 99.2%. The ammonia–mechanical pretreatment is an economical method for the production of fermentable monosaccharide, providing potential for further downstream high value-added applications. [ABSTRACT FROM AUTHOR]

Whisky lactone is a naturally occurring fragrance compound in oak wood and is widely used as a sensory additive in food products. However, safe and efficient methods for the production of its individual enantiomers for applications in the food industry are lacking. The aim of this study was to develop an efficient and highly stereoselective process for the synthesis of individual enantiomeric forms of whisky lactones. The proposed three-step method involves (1) column chromatography separation of a diastereoisomeric mixture of whisky lactone, (2) chemical reduction of cis-and transwhisky lactones to corresponding syn-and anti-diols, and (3) microbial oxidation of racemic diols to individual enantiomers of whisky lactone. Among various bacteria in the genera Dietzia, Gordonia, Micrococcus, Rhodococcus, and Streptomyces, R. erythropolis DSM44534 and R. erythropolis PCM2150 effectively oxidized antiand syn-3-methyl-octane-1,4-diols (1a-b) to corresponding enantiomerically pure cis-and trans-whisky lactones, indicating high alcohol dehydrogenase activity. Biooxidation catalyzed by whole cells of these strains yielded enantiomerically pure isomers of trans-(+)-(4S,5R) (2a), trans-(-)-(4R,5S) (2b), and cis-(+)-(4R,5R) (2d) whisky lactones. The optical density of bacterial cultures and the impact of the use of acetone powders as catalysts on the course of the reaction were also evaluated. Finally, the application of R. erythropolis DSM44534 in the form of an acetone powder generated the enantiomerically enriched cis-(-)-(4S,5S)-isomer (2c) from the corresponding syn-diol (1b). The newly developed method provides an improved approach for the synthesis of chiral whisky lactones. [ABSTRACT FROM AUTHOR]

DFT calculations on the full catalytic cycle for manganese catalysed enantioselective hydrogenation of a selection of ketones have been carried out at the PBE0‐D3PCM//RI‐BP86PCM level. Mn complexes of an enantiomerically pure chiral P,N,N ligand have been found to be most reactive when adopting a facial coordination mode. The use of a new ligand with an ortho‐substituted dimethylamino‐pyridine motif has been calculated to completely transform the levels of enantioselectivity possible for the hydrogenation of cyclic ketones relative to the first‐generation Mn catalysts. In silico evaluation of substrates has been used to identify those likely to be reduced with high enantiomer ratios (er), and others that would exhibit less selectivity; good agreements were then found in experiments. Various cyclic ketones and some acetophenone derivatives were hydrogenated with er's up to 99 : 1. [ABSTRACT FROM AUTHOR]

The synthesis of two series of monocyclic and bicyclic trifluoromethylated 4,5-dihydro-1,2,4-triazin-6(1H)-one derivatives based on (3+3)-annulation of methyl esters derived from natural α-amino acids with in situ generated trifluoroacetonitrile imines has been described. The devised protocol is characterized by a wide scope, easily accessible substrates, remarkable functional group tolerance, and high chemical yield. In reactions with chiral starting materials, no racemization at the stereogenic centers was observed and the respective enantiomerically pure products were obtained. Selected functional group interconversions carried out under catalytic hydrogenation and mild PTC oxidation conditions were also demonstrated. [ABSTRACT FROM AUTHOR]

As a class of widely used optical materials, KH2PO4 (KDP)-family crystals play an important role in the generation of infrared, visible, UV, and deep-UV lasers, but their deep-UV optical characteristics have been lacking in systematic research. Aiming at the typical KDP-family nonlinear crystals, including NH4H2PO4, KDP, K(H1−xDx)2PO4 (partially deuterated KDP), and KD2PO4 crystals, we systematically investigated their transmittance, cut-off edge, band-gap energy, linear absorption, and nonlinear two-photon absorption (TPA) properties in the deep-UV spectral region. By using a vacuum-UV spectrophotometer, the UV absolute transmittances were measured in the range of 160–290 nm. Based on the measured results, the UV cut-off edges of these crystals were obtained and band-gap energies were calculated. By using an Nd:YLF picosecond laser (1053 nm, 9 ps, 10 Hz), the fourth and fifth harmonics (263.2 and 210.5 nm) were generated respectively via a LiB3O5 crystal and two β-BaB2O4 crystals. The anisotropic linear absorption and nonlinear TPA coefficients of the above KDP-family crystals were obtained in detail from intensity-dependent transmittance measurements at 263.2 and 210.5 nm with ordinary and extraordinary polarization states. This comprehensive investigation of the deep-UV optical properties of commonly used KDP-family optical materials and the obtained new data can provide an important parameter basis for crystal growth with higher optical purity, deep-UV laser generation, and applications. [ABSTRACT FROM AUTHOR]

The reaction of chiral 2‐iodoferrocenecarboxamide, palladium(II) acetate, and triphenylphosphine ligand in acetonitrile has been resulted in the formation of an air‐stable chiral (Sp)‐2‐(N,N‐diisopropyl ferrocenecarboxamide) triphenylphosphine palladium(II) iodide complex. The isolated chiral palladium complex was thoroughly characterized by multi‐nuclear (1H, 13C, 31P) NMR, IR spectroscopy, mass spectrometry, polarimetry, CHN analysis, cyclic voltammetry and single crystal X‐ray crystallography (XRD). The single‐crystal XRD analysis reveals a square planar geometry around the palladium atom with a strong amide oxygen‐Pd bond [2.095(6) Å]. The palladium complex crystallized in the C2‐chiral space group having a Flack parameter value of 0.011(14), which is close to 0 and indicative of the enantiomeric purity of the palladium complex. The electrochemical study reveals a two‐electron redox couple due to the ferrocenyl Fe(II) atom and the palladacyclic Pd(II) center. In differential pulse voltammetry (DPV), two peaks were observed at 450 mV and 590 mV vs. Ag/AgCl. Further, the synthesized chiral palladacyle has also been explored in Suzuki‐Miyaura coupling reaction as a substrate and as a catalyst for Tsuji‐Trost coupling and phosphonation reactions. [ABSTRACT FROM AUTHOR]

Background: Recently, a lot of interest has been focused on the discovery of high L-tyrosinaseyielding microorganisms that catalyze the production of enantiomerically pure L-DOPA, which has been recognized as the conventional treatment for Parkinson's disease. Objectives: The current work primarily focused on isolating novel, promising tyrosinase-producing isolates and performing taxonomical characterization on them. Materials and Methods: Initially six various actinomycetes isolates were used in present study. Primary screening and secondary screening of selected isolates were performed. By evaluating the morphological, cultural, physiological, biochemical and molecular characterization, promising isolates were identified. Using 16S rRNA gene sequencing, the isolates' Phylogenetic investigations were conducted. Results: Streptomyces cellulosae variants, isolates PD18 and PD26 were identified to be the potential actinomycete isolates and their respective maximal tyrosinase yields were reported to be 21.20 IU/mL and 24.19 IU/mL. Conclusion: According to the observations of the experiment, SS (Soluble starch) medium with 1mg/mL copper sulphate was most suitable medium for tyrosinase production from our promising isolates PD18 and PD26. The maximum yield was noticed after 168 hr of incubation. This work emphasizes the significance of finding novel variants of Streptomyces cellulosae, which were first used to produce tyrosinase as well as promising sources for potentially bioactive substances like antimicrobial metabolites, biosurfactants and enzymes like amylase, lipase, cellulase, uricase, urease, ß-galactosidase and L-asparaginase. [ABSTRACT FROM AUTHOR]

Ibrutinib is an oral medication for the treatment of B cell malignancies. During its clinical development, a stable isotopologue of ibrutinib was required for the assessment of the drug's absolute oral bioavailability via intravenous microdosing. The following work describes a 10‐step, gram‐scale production of carbon‐13 labeled ibrutinib from [13C6]phenol (13C6, 99%) in 31% overall yield with >99% chemical purity and >99% enantiomeric excess (ee), suitable for intravenous microdosing in humans. [ABSTRACT FROM AUTHOR]

[18F]F-DOPA is widely used in PET diagnostics. Diseases diagnosed with this tracer are schizophrenia, Parkinson's disease, gliomas, neuroendocrine tumors, pheochromocytomas, and pancreatic adenocarcinoma. It should be noted that the [18F]F-DOPA tracer has been known for over 30 years. However, the methods of radiosynthesis applied in the past did not allow its clinical use due to low efficiency and purity. Currently, in the market, one encounters different types of radiosynthesis using the fluorine 18F isotope and variants of the same method. The synthesis and its modifications were carried out using a Raytest Synchrom R&D module. The synthesis consists of the following steps: (a) binding of the fluoride anion 18F− on an anion exchange column; (b) elution with TBAHCO3−; (c) nucleophilic fluorination to the ABX 1336 precursor; (d) purification of the intermediate product on the C18ec column; (e) Baeyer–Villiger oxidation; (f) hydrolysis; and (gfinal purification of the crude product on a semipreparative column. The nucleophilic synthesis of [18F]F-DOPA was successfully performed in 120 min, using the ABX 1336 precursor on the Raytest SynChrom R&D module, with a radiochemical yield (RCY) of 15%, radiochemical purity (RCP) ≥ 97%, and enantiomeric purity (ee) ≥ 96%. [ABSTRACT FROM AUTHOR]

Stereoselective synthesis has been emerging as a resourceful tool because it enables the obtaining of compounds with biological interest and high enantiomeric purity. Flavonoids are natural products with several biological activities. Owing to their biological potential and aiming to achieve enantiomerically pure forms, several methodologies of stereoselective synthesis have been implemented. Those approaches encompass stereoselective chalcone epoxidation, Sharpless asymmetric dihydroxylation, Mitsunobu reaction, and the cycloaddition of 1,4-benzoquinone. Chiral auxiliaries, organo-, organometallic, and biocatalysis, as well as the chiral pool approach were also employed with the goal of obtaining chiral bioactive flavonoids with a high enantiomeric ratio. Additionally, the employment of the Diels–Alder reaction based on the stereodivergent reaction on a racemic mixture strategy or using catalyst complexes to synthesise pure enantiomers of flavonoids was reported. Furthermore, biomimetic pathways displayed another approach as illustrated by the asymmetric coupling of 2-hydroxychalcones driven by visible light. Recently, an asymmetric transfer hydrogen-dynamic kinetic resolution was also applied to synthesise (R,R)-cis-alcohols which, in turn, would be used as building blocks for the stereoselective synthesis of flavonoids. [ABSTRACT FROM AUTHOR]

The β-blocker (S)-bisoprolol hemifumarate has been synthesised in 96% enantiomeric excess with 19% total yield in a six-step synthesis. A transesterification reaction of the racemic chlorohydrin 1-chloro-3-(4-((2-isopropoxyethoxy)methyl)phenoxy)propan-2-ol catalysed by lipase B from Candida antarctica resulted in the R-chlorohydrin in high enantiomeric purity. Reaction of this building block with isopropylamine in methanol gave (S)-bisoprolol, and further reaction with fumaric acid gave (S)-bisoprolol fumarate in 96% ee. Specific rotation value confirmed the absolute configuration of the enantiopure drug. [ABSTRACT FROM AUTHOR]

Immobilization of lipase AK from Pseudomonas fluorescens onto a microsphere support constructed by the metal organic framework (MOF) of NH 2 -Co-MOF was investigated. The loading capacity of 256.9 mg/g (MOF) with an immobilization yield of 72.3% was achieved. The further investigation demonstrated that AK@NH 2 -Co-MOF was an efficient catalyst in enantiospecific transesterification of 1-(4-bromophenyl) ethanol (BPE) with vinyl acetate, where the expressed activity of (4.028 ± 0.21)× 10−2 mmol/(min·mg AK@NH 2 -Co-MOF) was 8 times higher than the free lipase. Under the optimum conditions, BPE enantiomers were resolved by AK@NH 2 -Co-MOF with conversion of 50.42%, enantiomeric excess > 99% for remaining substrate (ee s) and enantiomeric excess > 99 % for product (ee p). AK@NH 2 -Co-MOF is recyclable and 51.62 % of the initial conversion was retained after 5 cycles of reuse. NH 2 -Co-MOF is promising for enzyme immobilization and the prepared AK@NH 2 -Co-MOF exhibited great potential for efficient biosynthesis of optically pure BPE. [Display omitted] • Covalent linkage of Pseudomonas fluorescens lipase to metal organic framework support. • Sought after products obtained in more than 99 % optical purity. • Enhanced activity as compared to the commercial lipase preparation. • Immobilized lipase reaches optimal parameters in half the time than free lipase. • Biocatalyst retains 52 % of initial conversion after 5 cycles of reuse. [ABSTRACT FROM AUTHOR]

Acetoin is an important four-carbon platform chemical with versatile applications. Optically pure (R)-acetoin is more valuable than the racemate as it can be applied in the asymmetric synthesis of optically active α-hydroxy ketone derivatives, pharmaceuticals, and liquid crystal composites. As a cytotoxic solvent, acetoin at high concentrations severely limits culture performance and impedes the acetoin yield of cell factories. In this study, putative genes that may improve the resistance to acetoin for Escherichia coli were screened. To obtain a high-producing strain, the identified acetoin-resistance gene was overexpressed, and the synthetic pathway of (R)-acetoin was strengthened by optimizing the copy number of the key genes. The engineered E. coli strain GXASR-49RSF produced 81.62 g/L (R)-acetoin with an enantiomeric purity of 96.5% in the fed-batch fermentation using non-food raw materials in a 3-L fermenter. Combining the systematic approach developed in this study with the use of low-cost feedstock showed great potential for (R)-acetoin production via this cost-effective biotechnological process. [ABSTRACT FROM AUTHOR]

Stereochemically pure phosphines with phosphorus‐heteroatom bonds and P‐centered chirality are a promising class of functional building blocks for the design of chiral ligands and organocatalysts. A route to enantiomerically pure primary aminophosphine sulfides was opened through stereospecific reductive C−N bond cleavage of phosphorus(V) precursors by lithium in liquid ammonia. The chemoselectivity of the reaction as a function of reaction time, substrate pattern, and chiral auxiliary was investigated. In the presence of exclusively aliphatic groups bound to the phosphorus atom, all competing reductive side reactions are totally prevented. The absolute configurations of all P‐stereogenic compounds were determined by single‐crystal X‐ray diffraction analysis. Their use as synthetic building blocks was demonstrated. The lithium salt of (R)‐BINOL‐dithiophosphoric acid proved to be a useful stereochemical probe to determine the enantiomeric purity. Insights into the coordination mode of the lithium‐based chiral complex formed in solution was provided by NMR spectroscopy and DFT calculations. [ABSTRACT FROM AUTHOR]

Strategies on the construction of enantiomerically pure silicon‐stereogenic silanes generally relies on desymmetrization of prochiral and symmetric substrates. However, dynamic kinetic asymmetric transformations of organosilicon compounds have remained underdeveloped and unforeseen owing to a lack of an effective method for deracemization of the static silicon stereocenters. Here we report the first Rh‐catalyzed dynamic kinetic asymmetric intramolecular hydrosilylation (DyKAH) with "silicon‐centered" racemic hydrosilanes that enables the facile preparation of silicon‐stereogenic benzosiloles in good yields and excellent enantioselectivities. The special rhodium catalyst controlled by non‐diastereopure‐type mixed phosphine‐phosphoramidite ligand with axial chirality and multiple stereocenters can induce enantioselectivity efficiently in this novel DyKAH reaction. Density functional theory (DFT) calculations suggest that the amide moiety in chiral ligand plays important role in facilitating the SN2 substitution of chloride ion to realize the chiral inversion of silicon center. [ABSTRACT FROM AUTHOR]

We studied the possibility of synthesizing optically pure (S)-(–)-1-(4-methylphenyl)ethanol from the corresponding 1-(4-methylphenyl)ethanone catalyzed by D. carotа cells. The effect of exogenous reducing agents on the enantioselectivity of the reduction and the yield of the product was studied. We found conditions that make it possible to obtain (S)-(–)-1-(4-methylphenyl)ethanol by biotransformation of 1-(4-methylphenyl)ethanone catalyzed by D. carota cells for 144 h with 98% yield (76% ee). Bioreduction of the initial 1-(4-methylphenyl)ethanone in the presence of 4% ethanol leads to a decrease in the yield of (S)-(–)-1-(4-methylphenyl)ethanol to 60%, but the optical purity reaches 98% ee. Transformation of 1-(4-methylphenyl)ethanone in the presence of glucose leads to the formation of (S)-(–)-1-(4-methylphenyl)ethanol in 76% yield, while the enantiomeric excess increases to 96% ee. [ABSTRACT FROM AUTHOR]

A high-performance liquid chromatographic method was developed for the simultaneous determination of the related substances—three potential synthesis-related chemical impurities and the distomer—of escitalopram. The separation capacity of seven different polysaccharide-type chiral columns, including three amylose-based (Lux Amylose-1, Lux i-Amylose-1, Lux Amylose-2) and four cellulose-based columns (Lux Cellulose-1, Lux Cellulose-2, Lux Cellulose-3, and Lux Cellulose-4) were screened in the polar organic and reversed-phase modes. Lux Cellulose-1, based on cellulose tris(3,5-dimethylphenylcarbamate) as the chiral selector with an acetonitrile-water mixture containing 0.1% diethylamine was identified as the most promising separation system. Using the "one factor at a time" optimization approach, the effect of column temperature, flow rate, and mobile phase constituents on separation performance was evaluated, and the critical resolution values were determined. A U-shaped retention pattern was obtained when plotting the retention factors of the citalopram enantiomers versus the water content of the binary mobile phases on the Lux Cellulose-1 column. A thermodynamic analysis revealed enthalpy-driven enantioseparation in both the polar organic and reversed-phase modes. For further method optimizations, an L9 orthogonal array table was employed. Using the optimized parameters (Lux Cellulose-1 column with 0.1% (v/v) diethylamine in water/acetonitrile 55/45 (v/v); 0.8 mL/min flow rate at 25 °C), baseline separations were achieved between all compounds. Our newly developed HPLC method was validated according to the ICH guidelines and its application was tested with a commercially available pharmaceutical formulation. The method proved to be suitable for routine quality control of related substances and the enantiomeric purity of escitalopram. [ABSTRACT FROM AUTHOR]

This paper reports on a series of five chiral Schiff base push‐pull compounds derived from enantiomerically pure (1R,2R)‐(−)‐1,2‐diaminocyclohexane. The NiII, CuII, ZnII and PdII complexes supported by a ferrocene‐containing unsymmetrically‐substituted N2O2 quadridentate Schiff base ligand were prepared via template reactions and isolated in 74–87 % yields. A combination of EA, IR, UV/vis and 1H/13C{1H} NMR spectroscopy, HRMS spectrometry, cyclic voltammetry and single‐crystal X‐ray analysis (for the proligand 2 and its NiII derivative 3), together with computational methods (DFT and TD‐DFT) was used to fully characterize and study the properties of all products. Both 2 and 3 crystallize in the orthorhombic non‐centrosymmetric space group P212121, with two (R,R)‐(−)‐chiral carbon atoms in their structure. Second‐order nonlinear polarizabilities β have been measured by using Harmonic Light Scattering at 1.91 μm, with the Pd(II) species showing the higher NLO response of 460×10−30 esu. [ABSTRACT FROM AUTHOR]

The metalation of N,N‐dimethylaminomethylferrocene in THF by the superbasic mixture of nBuLi/KOtBu proceeds readily at low temperatures to afford a bimetallic Li2K2 aggregate containing ferrocenyl anions and tert‐butoxide. Starting from an enantiomerically enriched ortho‐lithiated aminomethylferrocene, an enantiomerically pure superbase can be prepared. The molecular compound exhibits superbasic behavior deprotonating N,N‐dimethylbenzylamine in the α‐position and is also capable of deprotonating toluene. Quantum chemical calculations provide insight into the role of the bridging THF molecule to the possible substrate–reagent interaction. In addition, a benzylpotassium alkoxide adduct gives a closer look into the corresponding reaction site of the Lochmann–Schlosser base that is reported herein. [ABSTRACT FROM AUTHOR]

The synthetic equivalents of the enantiopure binaphthyl bis(aryne) atropisomers derived from BINOL (1,1′‐bi‐2,2′‐naphtol) featuring a stereogenic axis vicinal to the two reactive triple bonds can be generated for the first time in solution in an enantiospecific manner. Using a two‐step sequence based on the bidirectional [4+2] cycloaddition of furan derivatives followed by an aromatizative deoxygenation reaction, several 9,9'‐bianthracenyl‐based atropisomers could be prepared enantiospecifically in high enantiomeric purity. Alternatively, bidirectional reactions with anthracene, 2‐bromostyrene, and perylene as the arynophiles afforded very congested bis(benzotriptycene), bis(tetraphene) and bis(anthra[1,2,3,4‐ghi]perylene) nanocarbon atropisomers in equally high enantiomeric purity. In complement, cross reactions with two different arynophiles revealed possible. The unusual atropisomer prototypes described in this study open the way to enantiopure nanographene atropisomers designed for functions. [ABSTRACT FROM AUTHOR]

Crizotinib is a tyrosine kinase inhibitor approved for the treatment of non-small-cell lung cancer, but it is inefficient on brain metastases. Crizotinib is a substrate of the P-glycoprotein, and non-invasive nuclear imaging can be used to assess the brain penetration of crizotinib. Positron emission tomography (PET) imaging using fluorine-18-labeled crizotinib would be a powerful tool for investigating new strategies to enhance the brain distribution of crizotinib. We have synthesized a spirocyclic hypervalent iodine precursor for the isotopic labeling of crizotinib in a 2.4% yield. Because crizotinib is an enantiomerically pure drug, a chiral separation was performed to afford the (R)-precursor. A two-step radiolabeling process was optimized and automated using the racemic precursor to afford [18F](R,S)-crizotinib in 15 ± 2 radiochemical yield and 103 ± 18 GBq/µmol molar activity. The same radiolabeling process was applied to the (R)-precursor to afford [18F](R)-crizotinib with comparable results. As a proof-of-concept, PET was realized in a single non-human primate to demonstrate the feasibility of [18F](R)-crizotinib in in vivo imaging. Whole-body PET highlighted the elimination routes of crizotinib with negligible penetration in the brain (SUVmean = 0.1). This proof-of-concept paves the way for further studies using [18F](R)-crizotinib to enhance its brain penetration depending on the P-glycoprotein function. [ABSTRACT FROM AUTHOR]

An active pharmaceutical ingredient (API) is any substance in a pharmaceutical product that is biologically active. That means the specific molecular entity is capable of achieving a defined biological effect on the target. These ingredients need to meet very strict limits; chemical and optical purity are considered to be the most important ones. A continuous-flow synthetic methodology which utilizes a continuously flowing stream of reactive fluids can be easily combined with photochemistry, which works with the chemical effects of light. These methods can be useful tools to meet these strict limits. Both of these methods are unique and powerful tools for the preparation of natural products or active pharmaceutical ingredients and their precursors with high structural complexity under mild conditions. This review shows some main directions in the field of active pharmaceutical ingredients' preparation using continuous-flow chemistry and photochemistry with numerous examples of industry and laboratory-scale applications. [ABSTRACT FROM AUTHOR]

The enzymatic kinetic resolution (EKR) of racemic alcohols or esters is a broadly recognized methodology for the preparation of these compounds in optically active form. Although EKR approaches have been developed for the enantioselective transesterification of a vast number of secondary alcohols or hydrolysis of their respective esters, to date, there is no report of bio- or chemo-catalytic asymmetric synthesis of non-racemic alcohols possessing 1,2,3,4-tetrahydroquinoline moiety, which are valuable building blocks for the pharmaceutical industry. In this work, the kinetic resolution of a set of racemic 1,2,3,4-tetrahydroquinoline-propan-2-ols was successfully carried out in neat organic solvents (in the case of CAL-B and BCL) or in water (in the case of MsAcT single variants) using immobilized lipases from Candida antarctica type B (CAL-B) and Burkholderia cepacia (BCL) or engineered acyltransferase variants from Mycobacterium smegmatis (MsAcT) as the biocatalysts and vinyl acetate as irreversible acyl donor, yielding enantiomerically enriched (S)-alcohols and the corresponding (R)-acetates with E-values up to 328 and excellent optical purities (>99% ee). In general, higher ee-values were observed in the reactions catalyzed by lipases; however, the rates of the reactions were significantly better in the case of MsAcT-catalyzed enantioselective transesterifications. Interestingly, we have experimentally proved that enantiomerically enriched 1-(7-nitro-3,4-dihydroquinolin-1(2H)-yl)propan-2-ol undergoes spontaneous amplification of optical purity under achiral chromatographic conditions. [ABSTRACT FROM AUTHOR]

The lipase kinetic resolution (KR) of aryloxy-propan-2-yl acetates, via hydrolysis, produced enantiomerically pure/enantioenriched mexiletine intermediates and analogs. Racemic acetates rac-1-(2,6-dimethylphenoxy)propan-2-yl acetate (rac-5a), rac-1-(2,4-dimethylphenoxy)propan-2-yl acetate (rac-5b), rac-1-(o-tolyloxy)propan-2-yl acetate (rac-5c) and rac-1-(naphthalen-1-yloxy)propan-2-yl acetate (rac-5d) were used as substrates. A preliminary screening (24 h, phosphate buffer pH 7.0 with 20% acetonitrile as co-solvent, 30 °C and enzyme:substrate ratio of 2:1, m:m) was carried out with twelve lipases using acetate 5a as substrate. Two enzymes stood out in the KR of 5a, the Amano AK lipase from Pseudomonas fluorescens and lipase from Thermomyces lanuginosus (TLL) immobilized on Immobead 150. Under these conditions, both the (R)-1-(2,6-dimethylphenoxy)propan-2-ol [(R)-4a] and the remaining (S)-1-(2,6-dimethylphenoxy)propan-2-yl acetate [(S)-5a] were obtained with enantiomeric excess (ee) > 99%, 50% conversion and enantiomeric ratio (E) > 200. The KR study was expanded to racemic acetates 5b-d, leading to the corresponding chiral remaining acetates with ≥95% ee, and the alcohols 4b-d with ≥98% ee, and conversion values close to 50%. The best conditions for KRs of rac-5b-d involved the use of lipase from P. fluorescens or TLL immobilized on Immobead 150, 24 or 48 h and 30 °C. These intermediates had their absolute configurations determined using 1H NMR spectroscopy (Mosher's method), showing that the KRs of these acetates obeyed the Kazlauskas' rule. Molecular docking studies corroborated the experimental results, indicating a preference for the hydrolysis of (R)-5a-d. [ABSTRACT FROM AUTHOR]

D-amino acids are valuable building blocks for the synthesis of biologically active compounds and pharmaceuticals. The asymmetric synthesis of chiral amino acids from prochiral ketones using stereoselective enzymes is a well-known but far from exhausted approach for large-scale production. Herein, we investigated a pyridoxal-5′-phosphate-dependent D-amino acid transaminase from Haliscomenobacter hydrossis as a potential biocatalyst for the enzymatic asymmetric synthesis of optically pure aliphatic and aromatic D-amino acids. We studied the catalytic efficiency and stereoselectivity of transaminase from H. hydrossis in the amination of aliphatic and aromatic α-keto acids, using D-glutamate as a source of the amino group. We constructed a one-pot three-enzyme system, which included transaminase and two auxiliary enzymes, hydroxyglutarate dehydrogenase, and glucose dehydrogenase, to produce D-amino acids with a product yield of 95–99% and an enantiomeric excess of more than 99%. We estimated the stability of the transaminase and the cofactor leakage under reaction conditions. It was found that a high concentration of α-keto acids as well as a low reaction temperature (30 °C) can reduce the cofactor leakage under reaction conditions. The obtained results demonstrated the efficiency of transaminase from H. hydrossis in the asymmetric synthesis of enantiomerically pure D-amino acids. [ABSTRACT FROM AUTHOR]

This study presents the production of D -lactic acid with high enantiomeric purity using lignocellulosic hydrolysates from newly isolated lactic acid bacterial (LAB) strains. Six strains, 4 heterofermentative and 2 homofermentative, were investigated for their ability to grow and produce lactic acid on sugar beet pulp (SBP) hydrolysates, containing a mixture of hexose and pentose sugars. Among the strains tested, three were isolates designated as A250, A257 and A15, all of which belonged to the genus Leuconostoc. Only strain A250 could be reliably identified as Leuconostoc pseudomesenteroides based on cluster analysis of Maldi-ToF spectra. All strains produced D -lactic acid in the presence of SBP hydrolysates, but with varying optical purities. The homofermentative strains achieved higher D -lactic acid optical purities, but without assimilating the pentose sugars. Co-cultivation of the homofermentative strain Lactobacillus coryniformis subsp. torquens DSM 20005 together with the heterofermentative isolate A250 led to the production of 21.7 g/L D -lactic acid with 99.3 % optical purity. This strategy enabled the complete sugar utilization of the substrate. Nanofiltration of the SBP hydrolysate enhanced the enantiomeric purity of the D -lactic acid produced from the isolates A250 and A15 by about 5 %. The highest D -lactic acid concentration (40 g/L) was achieved in fed-batch cultures of A250 isolate with nanofiltered SBP, where optical purity was 99.4 %. The results of this study underline the feasibility of a novel isolate as an efficient D -lactic acid producer using lignocellulosic hydrolysates. • D -lactic acid production with high optical purity from. • Novel isolates were able to co-consume glucose and arabinose and produce D -lactic acid. • Co-cultivation of hetero- and homofermentative strains resulted in production of D -lactic acid with enhanced optical purity. • A newly isolated Leuconostoc pseudomesenteroides strain produced 40 g/L of D -lactate with 99.4 % optical purity. [ABSTRACT FROM AUTHOR]

Chiral sulfoxide is considered to be an ideal candidate ligand for transition-metal-catalyzed asymmetric reactions due to its ease of synthesis, stability, and exceptional S -stereological orientation control. This paper reviews the different types of asymmetrical reactions with chiral sulfoxide ligands in recent years, as well as a discussion of efficient methods for the preparation of some enantiomerically pure sulfoxides. 1 Introduction 2 Chiral Sulfoxides as Ligands in Metal-Catalyzed Asymmetric Catalysis 3 Synthesis of Chiral Sulfoxides 4 Conclusions [ABSTRACT FROM AUTHOR]

The aim of this study was to propose an alternative route for preparing chiral ß- and a-ionols by asymmetric oxidation with a heme acquisition system A (HasA) derived from symbiotic fluorescent bacteria as a biocatalyst. The HasA (6 g) in distilled water (300 mL) was stirred at 1150 rpm for 1 day at 40°C. Subsequently, a secondary alcohol (0.77 mmol) as a substrate in 2% 2-propanol was added to the catalyst solution. After verifying that the oxidation proceeded to ca 50% using gas chromatography (GC), the reaction mixture was filtered, extracted, washed, and dried over. The extract was concentrated in vacuo and purified using silica gel column chromatography to yield the oxidized product and recover the unreacted alcohol. ß-Ionol was oxidized into ß-ionone in a conversion of ca. 50% in the presence of the HasA for three days, and the remaining alcohol was recovered and analyzed using chiral GC after acetylation. The HasA selectively catalyzed the asymmetric oxidation of ß-ionol with a preference for the (R)- form to recover (S)- ß-ionol with 96.4 ±1.6% enantiomeric excess (ee). In addition, a-ionol was similarly oxidized into a-ionone in a conversion of ca. 50% for seven days, preferentially remaining (9S)-a-ionol with 97.9 ± 0.2% ee. The characteristic aroma of (S)-ß-ionol obtained by the asymmetric oxidation with the HasA showed floral and fruity like, while the aroma of (9S)-a-ionol described as violet and sweet. In this study, we successfully developed a new approach to prepare enantiomerically pure (S)-ß- and a-ionols by the asymmetric oxidation with the HasA. [ABSTRACT FROM AUTHOR]

Alcohol‐initiated ring‐opening polymerizations (ROPs) of L‐Lactide (LA) were conducted in bulk at 130 °C catalyzed by Zn acetate (ZnAc2), lactate (ZnLac2), or caprylate (ZnCap2). 11‐undecenol (UND), 1‐hydroxymethylnaphtalene (HMN), and 4‐nitrobenzylalcohol (4NB) were used as alcohols. Whereas variation of the alcohols had little effect, the usefulness of the catalysts increased in the order: acetate < lactate < caprylate. Hence, further alcohol‐initiated polymerizations were performed with ZnCap2 alone and with variation of the lactide/catalyst (LA/Cat) ratio. With increasing LA/Cat ratio higher fractions of cyclic poly(L‐lactide) (PLA) were found, so that the measured degree of polymerization (DP) is considerably lower than the theoretical value (i.e., 2 x LA/alcohol). With neat ZnCap2 cyclic PLAs were the largely prevailing reaction products. For these cyclic PLAs weight average molar masses (Mw) up to 134,000 were obtained and an optical purity around 99% was indicated by 13C NMR spectroscopy and DSC measurements even after 48 h at 150 or 160 °C. [ABSTRACT FROM AUTHOR]

This account describes the results of three decades of work on the production, chemistry, and synthetic applications of cis‐cyclohexadienediols obtained by biotransformation of arenes. These cis‐diols are valuable chiral building blocks, as they are enantiomerically pure, possessing good accessibility and high chemical versatility. Our work covers enzymatic and chemical aspects of the biotransformation, as well as synthetic applications of the resulting cis‐diols. We optimized the biotransformation procedure, described a computational model of TDO, designed new mutants, identified new metabolites, and disclosed new reactions of the Rieske dioxygenases. Also, the reactivity of the cis‐diol core was studied, with an emphasis in addition reactions, such as cycloadditions, osmylations, and electrophilic additions. Preparation of building blocks and bioactive natural products is described from the synthetic point of view, mostly concerning cyclitols, carbasugars, acetogenin and carbohydrates. [ABSTRACT FROM AUTHOR]

In this paper, we have realized the high purity non-diffracting optical vortex arrays with a high topological charge using quasi-symmetrical plane waves for the first time. The triangular vortex arrays with l = ±2 can be generated by six quasi-symmetrical plane waves, and the square vortex arrays with l = ±3 can be generated by eight quasi-symmetrical plane waves. The adjacent vortex units have opposite topological charges. We have also obtained the relations between the periods of the field formed by the six/eight quasi-symmetrical plane waves and the periods of the field formed by the three/four symmetrical plane waves. The simulation and experimental results demonstrate the feasibility of this method. • The high purity non-diffracting triangular vortex arrays with l =±2 can be generated by six quasi symmetric plane waves. • The high purity non-diffracting square vortex arrays with l =±3 can be generated by eight quasi symmetric plane waves. • The relationship between the periods of the field formed by six quasi symmetric plane waves or three symmetric plane waves. • The relationship between the periods of the field formed by eight quasi symmetric plane waves or four symmetric plane waves. [ABSTRACT FROM AUTHOR]

Metamifop (MET) is a widely used pesticides in paddy field and it has good weed control effect. As a chiral pesticide that may be hazardous to human health through food chain transmission, there could be selective differences in the metabolism and toxicity of its enantiomers, so the study of chiral MET may offer an assessment of MET toxicity and stereoselectivity at the enantiomeric level. A total of 39, 43 and 31 differential metabolites were screened from the data sets of Rac-, R-(-)- and S-(+)-MET, respectively. Metabolic pathway analysis revealed that MET and its enantiomers primarily affected sphingolipid metabolism, glycerophospholipid metabolism, linoleic acid metabolism, α-linolenic acid metabolism and arachidonic acid metabolism. Rac- and S-(+)-MET affected the synthesis of glycosylphosphatidylinositol (GPI)-anchored biomolecules. R-(-)- and S-(+)-MET affected glutathione metabolism. R-(-)-MET affected vitamin B6 metabolism, selenium compound metabolism, and steroid biosynthesis. Pyrimidine metabolism was only affected by Rac-MET. The experimental results indicated that MET and its enantiomers may affect the nervous and immune systems in rats. Further inter-group difference analysis also demonstrated stereoselectivity of MET and its enantiomers on rat serum metabolism. These findings may provide more detailed information on the toxicity of Rac-, S-(+)- and R-(-)-MET in rat, as well as some context for assessing the environmental risk of the three agents to organisms. • Racemic metamifop and its enantiomers exhibited different effects on metabolites in rat serum. • Rac- and S-(+)-MET affected the synthesis of glycosylphosphatidylinositol (GPI)-anchored biomolecules. • R-(-)- and S-(+)-MET affected glutathione metabolism. • Providing a scientific basis for assessing the health risks of MET and developing safer enantiomerically pure MET formulations. • This offers the prospect of studying the environmental risks of chiral pesticides at the molecular level in the future. [ABSTRACT FROM AUTHOR]