Racemic Research Articles

Scalable synthesis of sulfonium and selenonium peptides for selective methyllysine reader crosslinking

Lysine methylation readers are an important class of proteins that bind site-specifically methylated proteins for downstream regulation. Chemical probes that crosslink lysine methylation readers are highly desired to investigate the proteins from cellular samples. We recently reported NleS+me2 (norleucine-ε-dimethylsulfonium) as dimethyllysine mimic selectively crosslinks corresponding methyllysine readers. Although the sulfonium tools exhibited great promise, the synthetic availability may limit broad applications. In order to incorporate the unnatural amino acid, l-Fmoc-NleSme-OH (Fmoc: fluorenyl methoxycarbonyl) was synthesized as an important building block for solid-phase peptide synthesis (SPPS) in the previous synthetic route. It took six steps with resolution of racemic mixture and radical mediated thiol-ene reaction. As a result, the synthesis was not scalable with only 4.4 % overall yield. Here we report a much-improved synthesis method so that diverse NleS+me2 peptides could be readily prepared. In addition, the new method enables preparation of selenonium peptides for methyllysine reader crosslinking. We thus believe this synthetic method will be widely used to prepare sulfonium and selenonium probes for site-selective crosslinking.

Classics in Chemical Neuroscience: Medetomidine.

Medetomidine is an FDA-approved α2-adrenoreceptor (α2-AR) agonist used as a veterinary sedative due to its analgesic, sedative, and anxiolytic properties. While it is marketed for veterinary use as a racemic mixture under the brand name Domitor, the pharmacologically active enantiomer, dexmedetomidine, is approved for sedation and analgesia in the hospital setting. Medetomidine has recently been detected in the illicit drug supply alongside fentanyl, xylazine, cocaine, and heroin, producing pronounced sedative effects that are not reversed by naloxone. The pharmacological effects along with the low cost of supply and lack of regulation for medetomidine has made it a target for misuse. Since 2022, medetomidine has been found as an adulterant in samples of seized drugs, as well as in toxicological analyses of patients admitted to the emergency department after suspected overdoses across several U.S. states and Canada. This Review will discuss the history, chemistry, structure-activity relationships, drug metabolism and pharmacokinetics (DMPK), pharmacology, and emergence of medetomidine as an adulterant in drug mixtures in the context of the current opioid drug crisis.

Tuning the circularly polarized luminescence in homoleptic and heteroleptic chiral CrIII complexes.

A series of highly emissive inert and chiral CrIII complexes displaying positive and negative circularly polarized luminescence (CPL) within the near-infrared (NIR) region at room temperature have been prepared and characterized to decipher the effect of ligand substitution on the photophysical properties, more specifically on the chiroptical properties. The helical homoleptic [Cr(dqp-R)2]3+ (dqp = 2,6-di(quinolin-8-yl)pyridine; R = Ph, ≡-Ph, DMA, ≡-DMA (DMA = N,N-dimethylaniline)) and heteroleptic [Cr(dqp)(L)]3+ (L = 4-methoxy-2,6-di(quinolin-8-yl)pyridine (dqp-OMe) or L = N 2,N 6-dimethyl-N 2,N 6-di(pyridin-2-yl)pyridine-2,6-diamine (ddpd)) molecular rubies were synthesized as racemic mixtures and then resolved and isolated into their respective pure PP and MM enantiomeric forms by chiral stationary phase HPLC. The corresponding enantiomers show two opposite polarized emission bands within the 700-780nm range corresponding to the characteristic metal-centered Cr(2E'→4A2) and Cr(2T1 '→4A2) transitions with large g lum ranging from 0.14 to 0.20 for the former transition. In summary, this study reports the rational use of different ligands on CrIII and their effect on the chiroptical properties of the complexes.

Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms.

Research over the past years has compared the enantiomers (S)-ketamine (esketamine) and (R)-ketamine (arketamine) of the previously known racemic mixture called ketamine (R/S-ketamine). Esketamine has been found to be more potent, offering three times stronger analgesic effects and 1.5 times greater anesthetic efficacy than arketamine. It provides smoother anesthesia with fewer side effects and is widely used in clinical settings due to its neuroprotective, bronchodilatory, and antiepileptic properties. Approved by the FDA and EMA in 2019, esketamine is currently used alongside SSRIs or SNRIs for treatment-resistant depression (TRD). On the other hand, arketamine has shown potential for treating neurological disorders such as Alzheimer's, Parkinson's, and multiple sclerosis, offering possible antidepressant effects and anti-inflammatory benefits. While esketamine is already in clinical use, arketamine's future depends on further research to address its safety, efficacy, and optimal dosing. Both enantiomers hold significant clinical value, with esketamine excelling in anesthesia, and arketamine showing promise in neurological and psychiatric treatments.

New Active Ingredients for Sustainable Modern Chemical Crop Protection in Agriculture.

Today, the agrochemical industry faces enormous challenges to ensure the sustainable supply of high-quality food, efficient water use, low environmental impact, and the growing world population. The shortage of agrochemicals due to consumer perception, changing needs of farmers and ever-changing regulatory requirements is higher than the number of active ingredients that are placed on the market. The introduction of halogen atoms into an active ingredient molecule offers the opportunity to optimize its physico-chemical properties such as molecular lipophilicity. As early as 2010, around four-fifths of modern agrochemicals on the market contained halogen atoms. In addition, it becomes clear that modern agrochemicals have increasingly complex molecular structures with one or more stereogenic centers in the molecule. Today, almost half of modern agrochemicals are chiral molecules (herbicides, insecticides/acaricides/nematicides ≪ fungicides) and most of them consist of mixtures such as racemic mixtures of enantiomers, followed by mixtures of diastereomers and mixtures of pure enantiomers. Therefore, it is important that halogen-containing substituents or stereogenic centers are considered in the structural optimization of the active ingredients to ultimately develop sustainable agrochemicals in terms of efficacy, ecotoxicology, ease of use and cost-effectiveness.

Photochemical and Photocatalytic Deracemization Reactions

AbstractUnder photochemical conditions using an appropriate chiral catalyst, racemic mixtures of compounds can be converted into enantioenriched mixtures through distinguished pathways known as photochemical and photocatalytic deracemization reactions. In this graphical review, we highlight photochemical deracemization reactions that proceed in the presence of light as the key element along with a suitable chiral photocatalyst.

S-(+)-mecamylamine increases the firing rate of serotonin neurons and diminishes depressive-like behaviors in an animal model of stress

Mecamylamine, a noncompetitive blocker of nicotinic acetylcholine receptors (nAChRs), is the racemic mixture of two stereoisomers: S-(+)-mecamylamine (S-mec) and R-(−)-mecamylamine (R-mec), with distinct interactions with α4β2 nAChRs. It has been shown that mecamylamine increases glutamate release and excites serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN). In this study, we separately evaluated the effects of S-mec and R-mec on 5-HT neuron excitability. S-mec (3 μM) increased firing frequency by 40 %, while R-mec (3 μM) raised it by only 22 %. S-mec acts as a positive allosteric modulator on high-sensitivity (HS) α4β2 nAChRs at glutamate terminals, enhancing spontaneous excitatory postsynaptic currents (sEPSCs) in 5-HT neurons. Conversely, R-mec decreased sEPSCs by blocking HS α4β2 nAChRs and reduced GABA-mediated inhibitory currents (sIPSCs) by blocking α7 nAChRs at GABAergic terminals. These mechanisms make S-mec more effective than R-mec in enhancing 5-HT neuron firing. Moreover, combining S-mec with TC-2559, a selective agonist of HS α4β2 nAChRs, increased firing frequency by 65 %, exceeding the effect of S-mec alone. To validate these findings, we evaluated the antidepressant effects of S-mec (1 mg/kg) combined with TC-2559 or RJR-2403, another α4β2 nAChR agonist. This combination successfully reduced depression-like behaviors, suggesting a potential treatment strategy for patients resistant to conventional antidepressants.

Results of an application of sex attractant EFETOV-2 in Southeastern Anatolia of Türkiye (Turkey)

In recent years, intensive studies with or without the use of sex pheromones and sex attractants have significantly increased our knowledge on the Zygaenidae (Lepidoptera) fauna of Türkiye (Turkey). An application of sex attractants from the series ‘EFETOV-2’ (a patented name) synthesised at the Crimean Federal University has allowed us to detect some species hitherto unknown in Türkiye (for example Rhagades pruni ([Denis & Schiffermüller], 1775) and Jordanita globulariae (Hübner, 1793)) and clarify many distributions. In this work we present new data on the results of testing the attractant EFETOV-2 (a racemic mixture of (2R)-butan-2-yl dodec-2-enoate and (2S)-butan-2-yl dodec-2-enoate) in some regions of Southeastern Anatolia of Türkiye. Determination of Zygaenidae species and their distribution ranges was carried out in Batman, Diyarbakır and Mardin Provinces in 2022–2024. Two Procridinae species, viz. Adscita obscura (Zeller, 1847) (31 males) and Jordanita anatolica (Naufock, 1929) (142 males), were attracted to the lures EFETOV-2 in all studied provinces.

Magnetically Separable Chiral Poly(ionic liquid) Microcapsules Prepared Using Oil-in-Oil Emulsions.

This article presents a method for producing chiral ionic liquid-based polyurea microcapsules that can be magnetically separated. The method involves entrapping hydrophilic magnetic nanoparticles within chiral polyurea microspheres. The synthetic process for creating these magnetic polyurea particles involves oil-in-oil (o/o) nano-emulsification of an ionic liquid-modified magnetite nanoparticle (MNPs-IL) and an ionic liquid-based diamine monomer, which comprises a chiral bis(mandelato)borate anion, in a nonpolar organic solvent, toluene, and contains a suitable surfactant. This is followed by an interfacial polycondensation reaction between the isocyanate monomer, polymethylenepolyphenyl isocyanate (PAPI 27), and the chiral diamine monomer, which generates chiral polyurea microcapsules containing magnetic nanoparticles within their cores. The microcapsules generated from the process are then utilized to selectively adsorb either the R or S enantiomer of tryptophan (Trp) from a racemic mixture that is dissolved in water, in order to evaluate their chiral recognition capabilities. During the experiments, the magnetically separable chiral poly(ionic liquid) microcapsules, which incorporated either the R or S isomer of chiral bis(mandelato)borate, exhibited exceptional enantioselective adsorption performance. Thus, the chiral polymeric microcapsules embedded with the R-isomer of the bis(mandelato)borate anion demonstrated significant selectivity for adsorbing L-Trp, yielding a mixture with 70% enantiomeric excess after 96 h. In contrast, microcapsules containing the S-isomer of the bis(mandelato)borate anion preferentially adsorbed D-Trp, achieving an enantiomeric excess of 73% after 48 h.

Synthesis, Absolute Configuration, Biological Profile and Antiproliferative Activity of New 3,5-Disubstituted Hydantoins.

Hydantoins, a class of five-membered heterocyclic compounds, exhibit diverse biological activities. The aim of this study was to synthesize and characterize a series of novel 3,5-disubstituted hydantoins and to investigate their antiproliferative activity against human cancer cell lines. The new hydantoin derivatives 5a-i were prepared as racemic mixtures of syn- and anti-isomers via a base-assisted intramolecular amidolysis of C-3 functionalized β-lactams. The enantiomers of syn-5a and anti-hydantoins 5b were separated by preparative high-performance liquid chromatography (HPLC) using n-hexane/2-propanol (90/10, v/v) as the mobile phase. The absolute configuration of the four allyl hydantoin enantiomers 5a was assigned based on a comparison of the experimental electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectra with those calculated using density functional theory (DFT). The antiproliferative activity evaluated in vitro against three different human cancer cell lines: HepG2 (liver hepatocellular carcinoma), A2780 (ovarian carcinoma), and MCF7 (breast adenocarcinoma), and on the non-tumor cell line HFF1 (normal human foreskin fibroblasts) using the MTT cell proliferation assay. In silico drug-like properties and ADMET profiles were estimated using the ADMET Predictor ver. 9.5 and the online server admetSAR. Eighteen new 3,5-disubstituted hydantoins were synthesized and characterized. The compound anti-5c showed potent cytotoxic activity against the human tumor cell line MCF7 (IC50 = 4.5 µmol/L) and the non-tumor cell line HFF1 (IC50 = 12.0 µmol/L). In silico analyzes revealed that the compounds exhibited moderate water solubility and membrane permeability and are likely substrates for CYP3A4 and P-glycoprotein and have a high probability of antiarthritic activity.

Chiral spin selectivity and chiroptical activity in helical molecules.

Chiral structures, breaking spatial inversion symmetry, exhibit non-zero chiroptical activity (COA) due to the coupling between their electric and magnetic responses under external electromagnetic fields, an effect absent in achiral systems. Non-magnetic chiral structures also exhibit Chiral-Induced Spin Selectivity (CISS), primarily detected in two terminal measurements in the linear regime, where spin selection emerges without external magnetic influence. Despite the different origins of these physical phenomena, our model captures the relevant physics required to address CISS as an intrinsic molecular effect with the basic ingredients: (i) chirality/inversion asymmetry, (ii) meV atomic spin-orbit coupling, and (iii) decoherence as a source of reciprocity breaking. In this work, we derived how the electronic system couples with polarized electromagnetic radiation to yield a spin-dependent polarization rotation power, quantified through the Rosenfeld tensor, predicting characteristic spin signatures in the COA. The model also predicts that a net spin polarization manifests in the molecular terminations that have been surmised as an explanation for chiral species separation of racemic mixtures and interactions with surface magnetic domains. A recent sensitive spectroscopic measurement of electron transfer in donor-acceptor complexes is consistent with the standalone CISS effect.

Engineering an Epoxide Hydrolase for Chemoenzymatic Asymmetric Synthesis of Chiral Triazole Fungicide (S)- and (R)-Flutriafol.

Flutriafol, a globally utilized triazole fungicide in agriculture, is typically applied as a racemic mixture, but its enantiomers differ in bioactivity and environmental impact. The synthesis of flutriafol enantiomers is critically dependent on chiral precursors: 2,2-bisaryl-substituted oxirane [(2-fluorophenyl)-2-(4-fluorophenyl)oxirane, 1a] and 1,2-diol [1-(2-fluorophenyl)-1-(4-fluorophenyl)ethane-1,2-diol, 1b]. Here, we engineered a Rhodotorula paludigensis epoxide hydrolase (RpEH), obtaining mutant Escherichia coli/RpehH336W/L360F with a 6.4-fold enhanced enantiomeric ratio (E) from 5.5 to 35.4. This enabled a gram-scale resolution of rac-1a by E. coli/RpehH336W/L360F, producing (S)-1a (98.2% ees) and (R)-1b (75.0% eep) with 44.3 and 55.7% analytical yields, respectively. As follows, chiral (S)-flutriafol (98.2% ee) and (R)-flutriafol (75.0% ee) were easily synthesized by a one-step chemocatalytic process from (S)-1a and a two-step chemocatalytic process from (R)-1b, respectively. This chemoenzymatic approach offers a superior alternative for the asymmetric synthesis of flutriafol enantiomers. Furthermore, molecular dynamics simulations revealed insight into the enantioselectivity improvement of RpEH toward bulky 2,2-bisaryl-substituted oxirane 1a.

Stereoregular Poly(Phenyl Glycidyl Ethers): In Situ Formation of a Polyether Stereocomplex from a Racemic Monomer Mixture

Polymer stereocomplex formation represents a promising research area as it can improve thermal and mechanical properties of co‐crystallized polymer strands of opposite chirality. Polymers that form stereocomplexes commonly feature high stereoregularity and usually require sourcing from enantiopure monomer building blocks. Herein, we report the in situ polyether stereo­complex formation from racemic epoxide monomers, i.e., substituted methyl phenyl glycidyl ethers. The bio‐renewable glycidyl ethers were explored in both enantio‐ and isoselective ring‐opening polymerizations (ROPs), resulting in isotactic poly(phenyl glycidyl ether). While the enantio­selective ROP selectively resolves a single enantiomeric, isotactic polyether stereoisomer ([mm]P ≥ 78%), the isoselective ROP leads to the concurrent formation of both isotactic (R)‐ and (S)‐poly(phenyl glycidyl ether) stereoisomers ([mm]P ≥ 92%) and thus results directly in a stereoisomer blend, which forms a stereocomplex. This is one of only a few polymer stereocomplexes generated directly during polymerization from a racemic monomer mixture. Stereo­complexes of the different poly(phenyl glycidyl ether)s show an increase in melting temperature of up to 76 °C, relative to the enantiopure parent polymers. The position of the methyl group at the phenyl ring determines both stereocomplex formation and the thermal properties of the resulting materials.

Stereoregular Poly(Phenyl Glycidyl Ethers): In Situ Formation of a Polyether Stereocomplex from a Racemic Monomer Mixture.

Polymer stereocomplex formation represents a promising research area as it can improve thermal and mechanical properties of co-crystallized polymer strands of opposite chirality. Polymers that form stereocomplexes commonly feature high stereoregularity and usually require sourcing from enantiopure monomer building blocks. Herein, we report the in situ polyether stereo-complex formation from racemic epoxide monomers, i.e., substituted methyl phenyl glycidyl ethers. The bio-renewable glycidyl ethers were explored in both enantio- and isoselective ring-opening polymerizations (ROPs), resulting in isotactic poly(phenyl glycidyl ether). While the enantio-selective ROP selectively resolves a single enantiomeric, isotactic polyether stereoisomer ([mm]P ≥ 78%), the isoselective ROP leads to the concurrent formation of both isotactic (R)- and (S)-poly(phenyl glycidyl ether) stereoisomers ([mm]P ≥ 92%) and thus results directly in a stereoisomer blend, which forms a stereocomplex. This is one of only a few polymer stereocomplexes generated directly during polymerization from a racemic monomer mixture. Stereo-complexes of the different poly(phenyl glycidyl ether)s show an increase in melting temperature of up to 76 °C, relative to the enantiopure parent polymers. The position of the methyl group at the phenyl ring determines both stereocomplex formation and the thermal properties of the resulting materials.

Low‐Temperature Flexibility of Chiral Organic Crystals with Highly Efficient Second‐Harmonic Generation

Flexible crystals with unique mechanical properties have presented enormous applications in optoelectronics, soft robotics and sensors. However, there have been no reports of low‐temperature‐resistant flexible crystals with second‐order nonlinear optical properties (NLO). Here, we report the flexible chiral Schiff‐base crystals capable of efficient second harmonic generation (SHG). Both enantiomers and racemic modifications of these crystals are mechanically flexible in two directions at both room temperature and at ‐196 °C, although their mechanical responses differ. The enantiomers display SHG with an intensity of up to 12 times that of potassium dihydrogenphosphate (KDP) when pumped at 980 nm, and they also have high laser‐induced damage thresholds (LDT). Even when bent, the crystals retain strong second harmonic generation, although with a different intensity distribution depending on the polarization, compared to when they are straight. This work describes the first instance of flexible organic crystal with NLO properties and lays the foundation for the development of mechanically flexible organic NLO materials.

Third-Generation L-Lactic Acid Biorefinery Approaches: Exploring the Viability of Macroalgae Detritus

AbstractRising concerns over fossil fuel depletion and plastic pollution have driven research into biodegradable alternatives, such as polylactic acid (PLA). Microbial fermentation is preferred for lactic acid production due to its ability to yield enantiomerically pure lactic acid, which is essential for PLA synthesis, unlike the racemic mixture from chemical synthesis. However, commercial lactic acid production using first-generation feedstocks faces challenges related to cost and sustainability. Macroalgae offer a promising alternative with their rapid growth rates and carbon capture capabilities. This review explores recent technological advancements in macroalgae physicochemical characterization, optimization of fermentation conditions, and innovative pretreatment methods to enhance sugar conversion rates for L-LA production. It also covers downstream processes for L-LA recovery, presenting a complete macroalgal biorefinery system. Environmental impacts and economic prospects are assessed through exergy and techno-economic analyses. By valorizing macroalgae detritus, this study underscores its potential to support a sustainable biorefinery industry, addressing economic feasibility and environmental impact.

Total Syntheses of the Tropolone-Containing Sesquiterpene Olaximbriside A and Its Decarbonylated Counterpart Olaximbriside B.

The racemic modification of the α-tropolone-containing sesquiterpene olaximbriside A [viz. (±)-4)] has been prepared over 12 steps from the readily accessible decalin derivative 12. The last two of these steps involve a fully regiocontrolled substitution reaction of bromotropone 24. The aromatization of a stereoisomeric and co-produced form of compound 12 has provided (±)-olaximbriside B [(±)-5)].

Exploring the Effects of Chirality of 5-methyl-5-[4-(4-oxo-3H-quinazolin-2-yl) phenyl]imidazolidine-2,4-dione and its Derivatives on the Oncological Target Tankyrase 2. Atomistic Insights.

Tankyrases (TNKS) are homomultimers existing in two forms, viz. TNKS1 and TNKS2. TNKS2 plays a pivotal role in carcinogenesis by activating the Wnt//β-catenin pathway. TNKS2 has been identified as a suitable target in oncology due to its crucial role in mediating tumour progression. The discovery of 5-methyl-5-[4-(4-oxo-3H-quinazolin-2-yl) phenyl] imidazolidine-2,4-dione, a hydantoin phenylquinazolinone derivative which exists as a racemic mixture and in its pure enantiomer forms, has reportedly exhibited inhibitory potency towards TNKS2. However, the molecular events surrounding its chirality towards TNKS2 remain unresolved. Herein, we employed in silico methods such as molecular dynamics simulation coupled with binding free energy estimations to explore the mechanistic activity of the racemic inhibitor and its enantiomer forms on TNK2 at a molecular level Results: Favourable binding free energies were noted for all three ligands propelled by electrostatic and van der Waals forces. The positive enantiomer demonstrated the highest total binding free energy (-38.15 kcal/mol), exhibiting a more potent binding affinity to TNKS2. Amino acids PHE1035, ALA1038, and HIS1048; PHE1035, HIS1048 and ILE1039; and TYR1060, SER1033 and ILE1059 were identified as key drivers of TNKS2 inhibition for all three inhibitors, characterized by the contribution of highest residual energies and the formation of crucial high-affinity interactions with the bound inhibitors. Further assessment of chirality by the inhibitors revealed a stabilizing effect of the complex systems of all three inhibitors on the TNKS2 structure. Concerning flexibility and mobility, the racemic inhibitor and negative enantiomer revealed a more rigid structure when bound to TNKS2, which could potentiate biological activity interference. The positive enantiomer, however, displayed much more elasticity and flexibility when bound to TNKS2. Overall, 5-methyl-5-[4-(4-oxo-3H-quinazolin-2-yl) phenyl] imidazolidine-2,4-dione and its derivatives showed their inhibitory prowess when bound to the TNKS2 target via in silico assessment. Thus, results from this study offer insight into chirality and the possibility of adjustments of the enantiomer ratio to promote greater inhibitory results. These results could also offer insight into lead optimization to enhance inhibitory effects.

Chemical constituents of five Saxifraga species and their virucidal activities

The chemical constituents of Saxifraga stolonifera, S. fortunei, S. nipponica, S. cortusifolia, and S. rebunshirensis were investigated for structure and virucidal activity. In addition to the Saxifraga species-derived tannins, 30 compounds (1−30) were isolated from the five species. 5-Hydroxy-4-methoxy-3-O-(6-O-caffeoyl)-β-D-glucopyranosyl benzoic acid (1) and kaempferol 3-O-β-d-xylopyranosyl-(1 → 2)-β-D-xylopyranoside (2) were identified as undescribed compounds. Although 1 was isolated as the (E)-isomer of its caffeoyl moiety, under light it became over time a mixture of the (Z)-isomer (1a) and (E)-isomer (1). Kaempferol 3-O-β-d-xylopyranosyl-(1 → 2)-β-D-glucopyranoside (3) was an analog of 2 and a known compound, whose NMR assignment was reconsidered and described. 6-Isopropyl-5,5-dimethyldihydropyrimidine-2,4(1H,3H)-dione (30) was expected to be a racemic mixture based on its optical rotation and X-ray crystallography data. The virucidal activities of the isolated compounds (1–30) against influenza A virus, severe acute respiratory syndrome coronavirus 2, feline calicivirus, and murine norovirus were evaluated to identify the presence of compounds other than the Saxifraga species-derived tannins, which exhibited virucidal activities. Although the isolated compound activities were relatively weak compared to those of Saxifraga species-derived tannins, the potential virucidal activity of the compounds with galloyl groups was confirmed.

Near-complete chiral selection in rotational quantum states

Controlling the internal quantum states of chiral molecules for a selected enantiomer has a wide range of fundamental applications from collision and reaction studies, quantum information to precision spectroscopy. Achieving full enantiomer-specific state transfer is a key requirement for such applications. Using tailored microwave fields, a chosen rotational state can be enriched for a selected enantiomer, even starting from a racemic mixture. This enables rapid switching between samples of different enantiomers in a given state, holding great promise, for instance, for measuring parity violation in chiral molecules. Although perfect state-specific enantiomeric enrichment is theoretically feasible, achieving the required experimental conditions seemed unrealistic. Here, we realize near-ideal conditions, overcoming both the limitations of thermal population and spatial degeneracy in rotational states. We achieve over 92% enantiomer-specific state transfer efficiency using enantiopure samples. This indicates that 96% state-specific enantiomeric purity can be obtained from a racemic mixture, in an approach that is universally applicable to all chiral molecules of C1 symmetry. Our work integrates the control over internal quantum states with molecular chirality, thus expanding the field of state-selective molecular beams studies to include chiral research.