Ee Values Research Articles

Biocatalytic Stereoselective Synthesis of Chiral Precursors for Liposoluble β1 Receptor Blocker Nebivolol.

Asymmetric reduction of 2-chloro-1-(6-fluorochroman-2-yl)ethan-1-one (NEB-7) into 2-chloro-1-(6-fluorochroman-2-yl)ethan-1-ol (NEB-8) is the crucial step for synthesis of liposoluble β1 receptor blocker nebivolol. Four efficient and stereoselective alcohol dehydrogenases were identified, enabling the stereoselective synthesis of all enantiomers of NEB-8 at a substrate loading of 137 g·L-1 with ee values of >99% and high space-time yields. This study provides novel biocatalysts for the efficient synthesis of nebivolol precursors and uncovers the molecular basis for enantioselectivity manipulation by parametrization of Prelog's rule.

Tolterodine Tartrate Loaded Cationic Elastic Liposomes for Transdermal Delivery: In Vitro, Ex Vivo, and In Vivo Evaluations.

Tolterodine tartrate (TOTA) is a first-line therapy to treat overactive urinary bladder (OAB). Oral delivery causes high hepatic clearance, xerostomia, headache, constipation, and blurred vision. We addressed Hansen solubility parameter (HSP) and Design Expert oriented optimized cationic elastic liposomes for transdermal application. The experimental solubility was conducted in HSPiP predicted excipients to tailor formulations using surfactants, stearylamine, ethanol, and phosphatidylcholine (PC). These were evaluated for formulation characteristics. The optimized OTEL1 and OTEL1-G (gel) were compared against the drug solution (DS) and liposomes. In vitro and ex vivo studies were accomplished to investigate the insights into the mechanistic understanding of TOTA release and permeation ability. Finally, confocal laser scanning microscopy (CLSM) supported ex vivo results. HSP values of TOTA were closely related to tween-80, stearylamine, and human's skin. The size (153nm), %EE (87.6%), and PDI (0.25) values of OTEL1 were in good agreement to the predicted values (161nm, 80.4%, and 0.31) with high desirability (0.963). Spherical and smooth OTEL1 (including OTEL1-G and liposomes) vesicles followed non-Fickian drug release as compared to DS (Fickian) as evidence with n > 0.5 (Korsmeyer and Peppas coefficient). OTEL1 (containing lipid and surfactant as 90mg and 13.8mg, respectively) exhibited 2.6 and 1.8-folds higher permeation flux than DS and liposomes, respectively. Biocompatible cationic OTEL1 was safe and non-hemolytic. OTEL1 was promised as a lead vesicular approach and an alternative to conventional oral therapy to treat OAB in children and advanced age patients.

Candidaantarctica Lipase B mediated kinetic resolution: A sustainable method for chiral synthesis of antiproliferative β-lactams

Biocatalysis is a valuable industrial approach in active pharmaceutical ingredient (API) manufacturing for asymmetric induction and synthesis of chiral APIs. Herein, we investigated synthesis of a panel of microtubule-destabilising antiproliferative β-lactam enantiomers employing a commercially available immobilised Candida antarctica lipase B enzyme together with methanol and MTBE. The β-lactam ring remained intact during chiral kinetic resolution reactions, plausibly due to a bulky N-1 phenyl substituent on the β-lactam ring substrate. The predominant reaction mediated by CAL-B was methanol catalysed conversion of the β-lactam 3-acetoxy substituent to a 3-hydroxyl group, with preferential methanolysis of the 3S, 4S enantiomer. The unreacted substrate underwent progressive enantioenrichment to the 3R, 4R enantiomer. Substitution patterns on the B ring C3 meta position of the β-lactam scaffold greatly affected the rate of reaction. Halo substituents (fluoro-, chloro- and bromo-) reduced the rate of conversion compared to unsubstituted analogues, which in turn increased enantiomeric excess (ee). Ee values up to 86 % for the 3S, 4S 3-hydroxyl enantiomer were achieved. A double resolution approach for unreacted substrate yielded high ee values (>99 %) for the 3R, 4R 3-acetoxy enantiomer. CAL-B mediated methanolysis is a more sustainable method for resolution of racemic antiproliferative β-lactams compared to a previous technique of chiral diastereomeric resolution. Yields of β-lactams obtained using CAL-B are far superior than previously described, which will facilitate progression toward pre-clinical and clinical development. Biocatalysis is a useful tool in the toolbox of the medicinal chemist.

Crystallization resolution of racemic compounds via chiral surfactant

As one of the basic attributes of nature and the universe, chirality is valuable in biology, medicine, and materials science. However, enantiomer resolution remains a long-standing challenge. Herein, a novel surfactant for resolution of racemic compound with high performance has been outlined. Firstly, we synthesized a chiral surfactant and its chiral recognition ability to L-Alanine molecules was confirmed. Subsequently, the solid–liquid equilibrium curves were used to design the resolution route. The synthesized surfactant was further utilized to intensify the crystallization process of the racemic compound, resulting in a remarkable increase of L-Alanine products’ ee values from 0% to 99%. Finally, quantum chemical calculations and molecular dynamics simulations were employed to uncover the stereoselectivity recognition mechanism of surfactant to L-Alanine molecules. Overall, we propose a new idea for direct crystallization resolution of racemic Alanine by chiral surfactants that differs from the “rule of reversal”, which is highly attractive for chiral resolution.

Preparation and In-Vitro Characterization of Solid Lipid Nanoparticles Containing Artemisinin and Curcumin.

Malaria remains a formidable public health obstacle across Africa, Southeast Asia, and portions of South America, exacerbated by resistance to antimalarial medications, such as artemisinin-based combinations. The combination of curcumin and artemisinin shows promise due to its potential for dose reduction, reduced toxicity, synergistic effects, and suitability for drug delivery improvement. This research aims to enhance the solubility and dissolution rates of curcumin and artemisinin by employing Solid Lipid Nanoparticles (SLNs). Oral delivery of both drugs faces challenges due to their poor water solubility, inefficient absorption, and rapid metabolism and elimination. The study focuses on formulating and optimizing Solid Lipid Nanoparticles (SLNs) encapsulating artemisinin (ART) and curcumin (CUR). SLNs were developed using the hot homogenization method, incorporating ultrasonication. Drug-excipient compatibility was evaluated using Differential Scanning Calorimetry (DSC). Lipid and surfactant screening was performed to select suitable components. A 3² full factorial design was utilized to investigate the influence of lipid and surfactant concentrations on key parameters, such as entrapment efficiency (%EE) and cumulative drug release (%CDR). Additionally, evaluations of % entrapment efficiency, drug loading, particle size, zeta potential, and in-vitro drug release were conducted. Successful development of artemisinin and curcumin SLNs was achieved using a full factorial design, demonstrating controlled drug release and high entrapment efficiency. The optimized nanoparticles exhibited a size of 114.7nm, uniformity (PDI: 0.261), and a zeta potential of -9.24 mV. Artemisinin and curcumin showed %EE values of 79.1% and 74.5%, respectively, with cumulative drug release of 85.1% and 80.9%, respectively. The full factorial design indicated that increased lipid concentration improved %EE, while higher surfactant concentration enhanced drug release and %EE. Stability studies of the optimized batch revealed no alterations in physical or chemical characteristics. The study successfully developed Solid Lipid Nanoparticles (SLNs) for artemisinin and curcumin, achieving controlled drug release, high entrapment efficiency, and desired particle size and uniformity. This advancement holds promise for enhancing drug delivery of herbal formulations.

Chiral Diselenophosphoric Acids for Ion Pair Catalysis: A Novel Approach to Enhance Both Proton Donating and Proton Accepting Properties.

The activation of poorly reactive substrates via strong chiral acids is a central topic in asymmetric ion pair catalysis these days. Despite highly successful scaffolds such as N-triflylphosphoramides, these catalysts either lack C2-symmetry or provide multiple H-bond acceptor sites, leading to lower ee values for certain reactions. We present BINOL-based diselenophosphoric acids (DSA) as an extremely promising alternative. Using an intertwined approach of synthesis and NMR studies, we developed a synthetic approach to DSA with up to 98 % NMR yield. The obtained acids provide both very high proton donor and proton acceptor properties, a bifunctionality, which is key to catalytic applications. Indeed, first reactivity test proved the much higher acidity of DSA and its ability to initiate Mukaiyama-Mannich reaction and protodesilylation of silyl ethers. Together with their C2-symmetry, the single donor and single acceptor situation, the decreased tendency of self-association, and the straightforward synthesis with potential 3,3'-substitution, the DSA provide all features ideal for the further development of ion pair catalysis.

Combining binding pocket mutagenesis and substrate tunnel engineering to improve an (R)-selective transaminase for the efficient synthesis of (R)-3-aminobutanol

(R)-selective transaminases have the potential to act as efficient biocatalysts for the synthesis of important pharmaceutical intermediates. However, their low catalytic efficiency and unfavorable equilibrium limit their industrial application. Seven (R)-selective transaminases were identified using homologous sequence mining. Beginning with the optimal candidate from Mycolicibacterium hippocampi, virtual mutagenesis and substrate tunnel engineering were performed to improve catalytic efficiency. The obtained variant, T282S/Q137E, exhibited 3.68-fold greater catalytic efficiency (kcat/Km) than the wild-type enzyme. Using substrate fed-batch and air sweeping processes, effective conversion of 100 mM 4-hydroxy-2-butanone was achieved with a conversion rate of 93 % and an ee value > 99.9 %. This study provides a basis for mutation of (R)-selective transaminases and offers an efficient biocatalytic process for the asymmetric synthesis of (R)-3-aminobutanol.

Enantioselective Michael addition of malonates to α,β-unsaturated ketones catalyzed by rare-earth metal amides RE[N(SiMe3)2]3 with phenoxy-functionalized amino alcohol proligands

A combination of rare-earth metal amides RE[N(SiMe3)2]3 and chiral phenoxy-functionalized amino alcohol proligands was developed to realize the enantioselective Michael addition of malonates with unsaturated ketones. The reactions catalyzed by samarium amide Sm[N(SiMe3)2]3 were performed best together with the chiral proligand H3L1 (H3L1 = 2,4-di-tert-butyl-6-((((1S,2R)-2-hydroxy-1,2-diphenylethyl) amino)methyl)phenol) in DCE with good group tolerance, mostly in high to excellent yields (85–98 %) and good to excellent ee values (50− >99 %). The possible mechanism was also proposed.

WITHDRAWN: Folic acid Grafted, cell-penetrating peptide conjugated pH-sensitive hydrophobically modified Glycol chitosan nanoparticles for drug delivery in breast cancer

Nanocarriers are an outcome of the fast development of nanotechnology; however, delivering drugs to tumor sites effectively is still a major difficulty. A pH-responsive drug carrier with good cell penetration and targeting ability was developed to release the drug exactly to the cancer site and overcome these limitations.The drug carrier FA-TAT-HGCNPs/PTX, which is pH-responsive, uses folic acid (FA) and TAT peptide to deliver paclitaxel (PTX) for target folate-receptor-overexpressing breast cancer cells. 2-(diisopropylamino) ethyl methacrylate was connected to glycol chitosan (GC) to form HGCNPs. Then TAT and HGCNPs were conjugated and FA was grafted onto the HGCNPs’ hydroxyl group. Physicochemical characterizations of FA-TAT-HGCNPs was also evaluated. The maximum DLE and EE values of the FA-TAT-HGCNPs at pH 8.0 were 74.0 ± 2.22 % and 93.7 ± 2.8 %, respectively. FA-TAT-HGCNPs, for instance, showed stability during long-term storage and lyophilization while exhibiting pH-responsive dissociation properties. The synthesized drug carrier was characterized by FTIR, XRD, SEM, HRTEM, DLS, and Zeta analysis. MTT assay exhibited the high anticancer activity of the FA-TAT-HGCNPs/PTX against the MCF-7 cells, whereas drug-free ones are highly biocompatible. The pharmacokinetic results showed twice the bioavailability of FA-TAT-HGCNPs/PTX compared to HGCNPs/PTX. Unlike FA-HGCNPs/PTX, CLSM analysis showed that FA-TAT-HGCNPs/PTX had a significantly more efficient intracellular uptake in MCF-7 cells. These data have shown the transmembrane ability of TATpeptide,the targeting effects of folate decoration, and the synergistic interaction between them.According to these findings, PTX-loaded FA-TAT-HGCNPs offer a potentially effective nanoscale drug delivery system for the treatment of breast cancer.

Sequence-Guided Redesign of an Omega-Transaminase from Bacillus megaterium for the Asymmetric Synthesis of Chiral Amines.

ω-Transaminases (ω-TAs) are attractive biocatalysts asymmetrically catalyzing ketones to chiral amines. However, poor non-native catalytic activity and substrate promiscuity severely hamper its wide application in industrial production. Protein engineering efforts have generally focused on reshaping the substrate-binding pockets of ω-TAs. However, hotspots around the substrate tunnel as well as distant sites outside the pockets may also affect its activity. In this study, the ω-TA from Bacillus megaterium (BmeTA) was selected for engineering. The tunnel mutation Y164F synergy with distant mutation A245T which was acquired through a multiple sequence alignment showed improved soluble expression, a 3.7-fold higher specific activity and a 19.9-fold longer half-life at 45 °C. Molecule Dynamics simulation explains the mechanism of improved catalytic activity, enhanced thermostability and improved soluble expression of BmeTAY164F/A245T(2 M). Finally, the resting cells of 2 M were used for biocatalytic processes. 450 mM of S-methoxyisopropylamine (S-MOIPA) was obtained with an ee value of 97.3 % and a conversion rate of 90 %, laying the foundation for its industrial production. Mutant 2 M was also found to be more advantageous in catalyzing the transamination of various ketones. These results demonstrated that sites that are far away from the active center also play an important role in the redesign of ω-TAs.

α-Amino Acid Synthesis by 1,3-Nitrogen Migration: An Update

AbstractAn improved practical and efficient procedure for the synthesis of non-racemic unnatural α-amino acids through a stereocontrolled rearrangement is reported. Carboxylic acids are converted into azanyl esters RCO2NHBoc followed by an iron-catalyzed 1,3-nitrogen migration to provide non-racemic α-amino acids in an asymmetric (α-monosubstituted α-amino acids) or enantioconvergent fashion (α,α-disubstituted α-amino acids). Under optimized conditions using a fluorinated chiral iron catalyst and 2,2,6,6-tetramethylpiperidine as the base in a solvent mixture of 1,2-dichlorobenzene and CHCl3, enantioselectivities of up to 98% ee were obtained. Such high ee values are important for practical purposes, allowing the direct use of many of the obtained N-Boc-protected α-amino acids for subsequent applications.

Data-science-guided calibration curve prediction of an MLCT-based ee determination assay for chiral amines

Circular dichroism (CD) based enantiomeric excess (ee) determination assays are optical alternatives to chromatographic ee determination in high-throughput screening (HTS) applications. However, the implementation of these assays requires calibration experiments using enantioenriched materials. We present a data-driven approach that circumvents the need for chiral resolution and calibration experiments for an octahedral Fe(II) complex (1) used for the ee determination of α-chiral primary amines. By computationally parameterizing the imine ligands formed in the assay conditions, a model of the circular dichroism (CD) response of the Fe(II) assembly was developed. Using this model, calibration curves were generated for four analytes and compared to experimentally generated curves. In a single-blind ee determination study, the ee values of unknown samples were determined within 9% mean absolute error, which rivals the error using experimentally generated calibration curves.

Carborane-Cluster-Wrapped Copper Cluster with Cyclodextrin-like Cavities for Chiral Recognition.

Chiral atomically precise metal clusters, known for their remarkable chiroptical properties, hold great potential for applications in chirality recognition. However, advancements in this field have been constrained by the limited exploration of host-guest chemistry, involving metal clusters. This study reports the synthesis of a chiral Cu16(C2B10H10S2)8 (denoted as Cu16@CB8, where C2B10H12S2H2 = 9,12-(HS)2-1,2-closo-carborane) cluster by an achiral carboranylthiolate ligand. The chiral R-/S-Cu16@CB8 cluster features chiral cavities reminiscent of cyclodextrins, which are surrounded by carborane clusters, yet they crystallize in a racemate. These cyclodextrin-like cavities demonstrated the specific recognition of amino acids, as indicated by the responsive output of circular dichroism and circularly polarized luminescence signals of Cu16 moieties of the Cu16@CB8 cluster. Notably, a quantitative chiroptical analysis of amino acids in a short time and a concomitant deracemization of Cu16@CB8 were achieved. Density functional tight-binding molecular dynamics simulation and noncovalent interaction analysis further unraveled the great importance of the cavities and binding sites for chiral recognition. Dipeptide, tripeptide, and polypeptide containing the corresponding amino acids (Cys, Arg, or His residues) display the same chiral recognition, showing the generality of this approach. The functional synergy of dual clusters, comprising carborane and metal clusters, is for the first time demonstrated in the Cu16@CB8 cluster, resulting in the valuable quantification of the enantiomeric excess (ee) value of amino acids. This work opens a new avenue for chirality sensors based on chiral metal clusters with unique chiroptical properties and inspires the development of carborane clusters in host-guest chemistry.

Aquatic plants as whole-cell biocatalysts for preparing optically active β-hydroxy esters

We investigated the asymmetric reduction of β-keto esters using aquatic plants as whole-cell biocatalysts under darkness and illumination by fluorescent light. The (S)- β-hydroxy esters were obtained with high enantiomeric excess (ee) values. Regardless of the light conditions, the amount of (R)- β-hydroxy ester produced did not change significantly as the substrate concentration increased, whereas the yield of (S)- β-hydroxy ester increased substantially. Moreover, increasing the quantity of plants resulted in a significant increase in the production of (S)- β-hydroxy ester and a slight increase in the production of (R)- β-hydroxy ester, reducing the ee value. The reaction proceeded more efficiently for substrates bearing bulkier ester moieties, of which the tert-butyl ester gave the best results. Ultimately, we concluded that aquatic plants can be used as whole-cell biocatalysts for preparing optically active β-hydroxy esters. This result represents a new use of aquatic plants and contributes to the achievement of carbon neutrality.

Robust Homochiral Polycrystalline Metal-Organic Framework Membranes for High-Performance Enantioselective Separation.

Homochiral MOF membranes offer a promising route to efficient chiral separation, but their fabrication remains challenging. Here, we report for the first time the design and preparation of homochiral polycrystalline MOF-808 membranes for the first time. The membrane exhibits a high integrity and thin membrane thickness. Achieving homochirality through chiral amino acid postsynthetic modification, MOF-808 membranes demonstrate remarkable solvent stability. Notably, they successfully separated racemic naproxen enantiomers, achieving enantiomeric excess (ee) values of up to ∼95.0%. This work paves the way for turning achiral polycrystalline MOF membranes into high-performance chiral membranes for enantioselective separation.

A Practical Method for Synthesizing Iptacopan.

Iptacopan, the first orally available small-molecule complement factor B inhibitor, was developed by Novartis AG of Switzerland. Iptacopan for the treatment of PNH was just approved by the FDA in December 2023. Other indications for treatment are still in phase III clinical trials. Iptacopan is a small-molecule inhibitor targeting complement factor B, showing positive therapeutic effects in the treatment of PNH, C3 glomerulonephritis, and other diseases. Although Iptacopan is already on the market, there has been no detailed synthesis process or specific parameter report on the intermediates during the synthesis of its compounds except for the original research patent. In this study, a practical synthesis route for Iptacopan was obtained through incremental improvement while a biosynthesis method for ketoreductase was used for the synthesis of the pivotal intermediate 12. Moreover, by screening the existing enzyme library of our research group on the basis of random as well as site-directed mutagenesis methods, an enzyme (M8) proven to be of high optical purity with a high yield for biocatalectic reduction was obtained. This enzyme was used to prepare the compound benzyl (2S,4S)-4-hydroxy-2-(4-(methoxycarbonyl)-phenyl)-piperidine-1-carboxylate) white powder (36.8 g HPLC purity: 98%, ee value: 99%). In the synthesis of intermediate 15, the reaction was improved from two-step to one-step, which indicated that the risk of chiral allosterism was reduced while the scale was expanded. Finally, Iptacopan was synthesized in a seven-step reaction with a total yield of 29%. Since three chiral intermediate impurities were synthesized directionally, this paper lays a solid foundation for the future of pharmaceutical manufacturing.

Essential amino acid residues and catalytic mechanism of trans-epoxysuccinate hydrolase for production of meso-tartaric acid.

This study aimed to discuss the essential amino acid residues and catalytic mechanism of trans-epoxysuccinate hydrolase from Pseudomonas koreensis for the production of meso-tartaric acid. The optimum conditions of the enzyme were 45°C and pH 9.0, respectively. It was strongly inhibited by Zn2+, Mn2+ and SDS. Michaelis-Menten enzyme kinetics analysis gave a Km value of 3.50mM and a kcat of 99.75s-1, with an exceptional EE value exceeding 99.9%. Multiple sequence alignment and homology modeling revealed that the enzyme belonged to MhpC superfamily and possessed a typical α/β hydrolase folding structure. Site-directed mutagenesis indicated H34, D104, R105, R108, D128, Y147, H149, W150, Y211, and H272 were important catalytic residues. The 18O-labeling study suggested the enzyme acted via two-step catalytic mechanism. The structure and catalytic mechanism of trans-epoxysuccinate hydrolase were first reported. Ten residues were critical for its catalysis and a two-step mechanism by an Asp-His-Asp catalytic triad was proposed.

Asymmetric Synthesis of Three Alkenyl Epoxides: Crafting the Sex Pheromones of the Elm Spanworm and the Painted Apple Moth.

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

Digestibility and nutritional parameters of maize ethanol coproducts and xylanase for broiler diets

ABSTRACT 1. The objective of this study was to determine the nutritional and energy values of four maize distiller’s dried grains with solubles (DDGS) and one maize high protein distiller’s dried grains (HP-DDG) from ethanol production plants in Brazil; to evaluate the digestibility, performance, nitrogen balance and energy values for broiler chickens fed diets containing these coproducts (Experiment I); and to evaluate the effects of xylanase inclusion in diets containing maize DDGS for broilers on energy availability, digestibility, nitrogen balance and gastrointestinal morphometry (Experiment II). 2. For each experiment, 180 broiler chickens aged 17 and 30 days with initial weights of 450 ± 18 g and 1228 ± 33 g, respectively, were used; the chickens were distributed into 36 metabolism cages. The experimental design consisted of complete randomised blocks, with six replications per treatment and five birds per experimental unit. The treatments consisted of a basal diet (BD) and five test diets containing maize ethanol coproducts (Experiment I) one BD and five test diets containing DDGS with inclusions of 0, 8,000, 16,000, 24,000 and 32,000 BXU/kg xylanase (Experiment II). In Experiment I, HP-DDG and DDGS2 presented higher AME and AMEn values (14.1 and 13.9 MJ/kg and 13.4 and 13.3 MJ/kg, respectively), than did the other coproducts (p < 0.05). Compared with DDGS1 and DDGS3, DDGS4 and HP-DDG had higher digestible CP values (p < 0.05). In Experiment II, the inclusion of the enzyme quadratically affected the values of digestible CP and digestible EE (p < 0.05), with the maximum values occurring with the inclusion of 18 750 and 22,170 BXU/kg of xylanase, respectively. 3. The digestible NDF and digestible MM values linearly increased with the inclusion of xylanase (p < 0.05). The addition of xylanase had no effect on gastrointestinal morphometry (p > 0.05). It was concluded that the inclusion of between 18,000 and 22,000 BXU/kg of xylanase resulted in better digestible CP and digestible EE values.

Asymmetric Synthesis of Dihydropyrimidinethione Podand in the Presence of C2‐Symmetric Bis(Hydroxy)Proline‐Containing Amides

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