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The biocatalytic asymmetric reduction of prochiral ketones offers a promising approach for producing optically active secondary alcohols. Alcohol dehydrogenases (ADHs) are enzymes that facilitate the reversible conversion of prochiral ketones into their corresponding optically active secondary alcohols, and thus are pivotal for this process. Most ADHs adhere to Prelog's rule in determining the stereopreference for the asymmetric reduction of prochiral ketones. This study focuses on the ΔP84/A85G mutation of TeSADH, demonstrating its capability to reduce aryl‐ring‐containing ketones to their corresponding alcohols in anti‐Prelog mode with high stereoselectivities. The study also highlights the crucial role of P84 in switching the stereopreference of TeSADH in the asymmetric reduction of aryl‐ring‐containing ketones. Furthermore, this mutant exhibits a broad substrate scope, including substrates accepted by the previously reported W110 mutants of TeSADH with opposite stereopreference. The ability to create mutants of the same enzyme with opposite stereopreferences presents intriguing opportunities for fascinating transformations, such as bienzymatic racemization, which can be utilized in dynamic kinetic resolution, and stereoinversion using two enantiocomplementary mutants of the same enzyme. [ABSTRACT FROM AUTHOR]

The increasing interest in axially chiral biaryl moieties, which are prevalent in chiral ligands, organocatalysts, and bioactive molecules, has raised the need for developing novel efficient synthetic methods for these types of molecules. In addition to the currently available methods, such as kinetic resolution, desymmetrization and enantio‐ and diastereo‐selective biaryl coupling, we herein report a lipase‐catalyzed dynamic kinetic resolution (DKR) of racemic 2‐hydroxybiaryls through enantioselective O‐acylation. This method features the production of enantiomerically enriched atropisomers (89 %–98 % ee) in 91 %–99 % yields from eleven racemates. Notably, the DKR proceeds without any racemization catalyst since in situ‐racemization was achieved by easy rotation about the biaryl axis of the substrates. The enzymatic O‐acylation then furnished conformationally stable biaryl‐containing esters, in which the increased steric bulkiness of the O‐acyl moiety suppresses the rotation, i. e., racemization, under the reaction conditions of 35–50 °C. This experimental study was accompanied by a computational determination of the rotational barrier of substrates and products. The choice of suitable substrates with a significant difference in their rotational barrier compared to that of their products turned out to be the key to an efficient implementation of this method. [ABSTRACT FROM AUTHOR]

An enantioconvergent palladium‐catalyzed Negishi cross‐coupling with racemic secondary organozinc reagents has been developed, enabling access to enantioenriched 1,1‐diarylalkane motifs in high yields and enantioselectivities. Computational data indicates that the racemization of organozinc compounds most likely occurs through a bridged bimolecular mechanism. [ABSTRACT FROM AUTHOR]

We herein report the facile synthesis of two helical carbon nanorings with small ring sizes, cyclo[6]paraphenylene‐1,5‐naphthylene ([6]CPPNap1,5), and cyclo[6]paraphenylene‐1,5‐anthrylene ([6]CPPAn1,5). The structures were determined by NMR and HR‐MS. X‐ray single‐crystal data of [6]CPPNap1,5 was also achieved. The strain energy and racemization processes were investigated by DFT calculations. The reduced ring sizes result in increased ring strain and elevated energy barriers. The photophysical properties were studied by UV‐Vis absorption, fluorescence emission, and time‐resolved fluorescence decay. [ABSTRACT FROM AUTHOR]

The synthesis of enantioenriched α‐substituted 1,3‐dicarbonyls remains a contemporary challenge in synthesis due to their tendency to undergo racemization via keto‐enol tautomerization. Herein, we report a method to access enantioenriched β‐ketoamides by a chiral sulfinimine‐mediated [3,3]‐sigmatropic sulfonium rearrangement. The transformation displays good chirality transfer, as well as excellent chemoselectivity and functional group tolerance. Diastereoselective reduction of the ketone moiety, also achievable in one‐pot fashion, affords enantioenriched β‐hydroxyamides. [ABSTRACT FROM AUTHOR]

Racemisation without Consequence: MOM deprotection during a routine synthesis of phosphoric acid 1 promoted partial racemisation of the product BINOL 5. Surprisingly, however, after phosphorylation of the partially racemised BINOL, enantiopure acid 1 was isolated. Further inspection revealed that during phosphorylation, unhydrolysed racemic phosphorochloridate 6 precipitated, thus restoring homochirality in the product phosphoric acid 1. Moreover, MOM deprotection partial racemisation was avoided by conducting reactions at lower temperatures for no longer than the required deprotection time, and/or by application of other deprotection conditions from the literature. [ABSTRACT FROM AUTHOR]

The ubiquitous nature of amines in drug compounds, bioactive molecules and natural products has fueled intense interest in their synthesis. Herein, we introduce a nickel‐catalyzed enantioconvergent allenylic amination of methanol‐activated allenols. This protocol affords a diverse array of functionalized allenylic amines in high yields and with excellent enantioselectivities. The synthetic potential of this method is demonstrated by employing bioactive amines as nucleophiles and conducting gram‐scale reactions. Furthermore, mechanistic investigations and DFT calculations elucidate the role of methanol as an activator in the nickel‐catalyzed reaction, facilitating the oxidative addition of the C−O bond of allenols through hydrogen‐bonding interactions. The remarkable outcomes arise from a rapid racemization of allenols enabled by the nickel catalyst and from highly enantioselective dynamic kinetic asymmetric transformation of η3‐alkadienylnickel intermediates. [ABSTRACT FROM AUTHOR]

Axially chiral diaryl ethers represent a distinct class of atropisomers, characterized by a unique dual C─O axes system, which have been found in a variety of natural products, pharmaceuticals, and ligands. However, the catalytic enantioselective synthesis of these atropoisomers poses significant challenges, due to the difficulty in controlling both chiral C─O axes, and their more flexible conformations. Herein, an efficient protocol for catalytic enantioselective synthesis of axially chiral diaryl ethers is presented using organocatalyzed asymmetric Povarov reaction‐enabled desymmetrization, followed by aromatizations. This method yields a wide range of novel quinoline‐based diaryl ether atropoisomers in good yields and high enantioselectivities. Notably, various aromatization protocols are developed, resulting in a diverse set of polysubstituted quinoline‐containing diaryl ether atropisomers. Thermal racemization studies suggested excellent configurational stabilities for these novel diaryl ether atropisomers (with racemization barriers up to 38.1 kcal mol−1). Moreover, this research demonstrates for the first time that diaryl ether atropisomers lacking the bulky t‐Bu group can still maintain a stable configuration, challenging the prior knowledge in the field. The fruitful derivatizations of the functional group‐rich chiral products further underscore the value of this method. [ABSTRACT FROM AUTHOR]

Given the scientifically significant importance of studying the chirality of clusters, the challenges of synthesizing chiral clusters are progressively surmounted. However, the racemization of clusters is unavoidable, and it limits the development of their follow‐on chiral applications. To address this issue, chiral thiols are synthesized and used for the construction of high‐stability optically pure nanoclusters in this work. As a result, a pair of chiral nanoclusters, Au24Cd2(SR)14, is obtained with excellent stability under thermal, acidic, alkaline, oxidizing, and reducing environments. Unexpectedly, it can also maintain its optical activity with the introduction of Cu2+ ions and chiral ligand with opposite configuration. Structural relationship analysis indicates that the excellent stability is mainly dependent on the hierarchical assembly of the nanoclusters, in which the chiral assembly of chiral ligands (a new pattern of chiral arrangement of intramolecular ligands on the surface of clusters) may be a key factor. [ABSTRACT FROM AUTHOR]

1H NMR measurements are reported for the C6D6 solution of the complex bis(tris(tert-butyl)cyclopentadienyl)neodymium(III) iodide [Cp′′′2NdI] {where Cp′′′ = 1,3,4-tris(tert-butyl)cyclopentadienide}. Temperature dependences of the 1H NMR spectra of the complex have been analyzed using the bandshape analysis, taking into account the temperature variation of the paramagnetic chemical shifts, within the frame of the dynamic NMR method. The conformational dynamics of the complex are conditioned by the process of racemization (with the value of the Gibbs activation energy ΔG ‡298 = 58 ± 3 kJ mol−1). Due to the substantial temperature dependence of the paramagnetic shifts, the complex is essentially an NMR thermosensor reagent for local temperature monitoring. Good agreement between the calculated and experimental lanthanide-induced paramagnetic shifts in the 1H NMR spectra indicates the similarity of the structure of the complex in a solution of C6D6 and the structure in the crystalline phase, found from the data of the X-ray structural study of the similar complex. [ABSTRACT FROM AUTHOR]

A novel, industrially viable synthetic route to (+)‐biotin has been developed starting from L‐cysteine via the known key thiolactone intermediate. The route takes advantage of the in‐built stereochemistry of the cysteine starting material and the best features of the two current industrialized processes. The key transformations are the conversion of L‐cysteine into a hydantoin avoiding racemization followed by catalytic cyanation and thiolactonization to form the required thiolactone intermediate. This known intermediate can be readily further transformed into (+)‐biotin. [ABSTRACT FROM AUTHOR]

Introduction: The successful synthesis of a peptide requires the synchronization of several processes, including the efficient execution of protecting group chemistry. For cysteine (Cys)-peptides, this is more crucial because the trifunctional Cys has a free thiol in its side chain. During synthesis, this free thiol function remains protected with suitable protecting groups and can be removed after synthesis using appropriate methods. Sec-isoamyl mercaptan (SIT) is a versatile disulfide-based protecting group for Cys side chain thiol. The removal of SIT from Cys thiol can be achieved using a mild reducing agent (e. g. DTT). This later promotes efficient disulfide bond formation by oxidation. SIT can also direct/activate the Cys thiol for the chemoselective formation of disulfide bonds by thiol-disulfide interchange. Methods: Peptides were synthesized using solid-phase peptide synthesis techniques. The removal of the SIT group was carried out either in the solid phase or in the solution. Results: In the present study, we have shown that SIT can be efficiently removed both in solution and on-resin to facilitate disulfide-bridged peptide synthesis. This was exemplified by two syntheses of an atosiban derivative, where the SIT was removed in solution or in solid-phase. Furthermore, a SIT-based facile one-pot synthesis pathway was devised for disulfide-rich peptides. The strategy was faster and greener as it did not involve using an oxidizer. Conotoxin (two S–S) and linaclotide amide (three S–S) were successfully synthesized by adopting the SIT-based strategy. Finally, a racemization study was carried out for SIT, Trt and StBu-protected Cys-peptides. In all cases, SIT-protected peptides showed lesser racemization than StBu-protected peptides. In some instances (synthesis using DMF), SIT-protected peptides showed less racemization compared to the Trt congeners. Conclusion: Overall, the multifaceted use of SIT-protection during the synthesis of disulfide-rich peptides has illustrated its versatility as a Cys thiol protecting group. [ABSTRACT FROM AUTHOR]

We report a mild, operationally simple, convenient, and rapid method of peptide bond formation using triphenylphosphine and iodine. The developed protocol was utilized to couple coded, non‐coded, and challenging amino acids in 64–92 % yield. Sterically hindered α,α‐disubstituted amino acids, which are important constituents of natural peptides, were also coupled in good yield. Mild reaction conditions in open air produce peptide bonds in a short time (30 min) without racemization. [ABSTRACT FROM AUTHOR]

A novel axially chiral all-hydrocarbon cyclo[7] (1,3-(4,6-dimethyl)benzene (CDMB-7) was designed and synthesized using atroposelective[2 + 5] cyclization through Suzuki–Miyaura coupling. CDMB-7 adopts an irregular bowl-like shape with C2 symmetry and exhibits two diastereoisomers in its crystallographic structure. The conformational isomers of CDMB-7 racemates remain stable at high temperatures (393 K). High-performance liquid chromatography (HPLC) confirmed that a single chiral isomer will spontaneously undergo racemization within 30 min at room temperature. This finding opens up possibilities for achieving adaptive chirality in all-hydrocarbon cyclo[7] m-benzene macrocycles. [ABSTRACT FROM AUTHOR]

Site-specific modifications of aspartate residues spontaneously occur in crystallin, the major protein in the lens. One of the primary modification sites is Asp151 in αA-crystallin. Isomerization and racemization alter the crystallin backbone structure, reducing its stability by inducing abnormal crystallin–crystallin interactions and ultimately leading to the insolubilization of crystallin complexes. These changes are considered significant factors in the formation of senile cataracts. However, the mechanisms driving spontaneous isomerization and racemization have not been experimentally demonstrated. In this study, we generated αA-crystallins with different homo-oligomeric sizes and/or containing an asparagine residue at position 151, which is more prone to isomerization and racemization. We characterized their structure, hydrophobicity, chaperone-like function, and heat stability, and examined their propensity for isomerization and racemization. The results show that the two differently sized αA-crystallin variants possessed similar secondary structures but exhibited different chaperone-like functions depending on their oligomeric sizes. The rate of isomerization and racemization of Asp151, as assessed by the deamidation of Asn151, was also found to depend on the oligomeric sizes of αA-crystallin. The predominant isomerization product via deamidation of Asn151 in the different-sized αA-crystallin variants was L-β-Asp in vitro, while various modifications occurred around Asp151 in vivo. The disparity between the findings of this in vitro study and in vivo studies suggests that the isomerization of Asp151 in vivo may be more complex than what occurs in vitro. [ABSTRACT FROM AUTHOR]

Temperature-Cycle-Induced Deracemization (TCID) offers a promising approach to obtain enantiopure solids from racemic mixtures. By combining rapid racemization in solution and temperature swings, homochirality is theoretically achieved. Despite theoretical expectations of doubled yields compared to traditional chiral separation methods, such as in Preferential Crystallization, experimental validation remains lacking. We applied TCID to (1-(4-chlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl)pentan-3-one) (Cl-TAK), introducing a post-TCID cooling step to enhance yield and a washing step to augment enantiopurity. This refinement yielded an 89.8% mass yield with 99.1% enantiomeric excess in the crystal phase (c.e.e.) within 24 h on an 8.75 g scale, showcasing improved performance with insignificant process duration extension. Additionally, we explored the stochasticity of deracemization, observing the development from low initial crystal enantiomeric excesses (1–6% c.e.e0) at a 2.5 g scale. Kinetic analysis revealed that a 2% c.e.e0 effectively mitigates chiral flipping risks and induction time in our system. Our study underscores the potential for reduced initial c.e.e. to expedite deracemization and presents a straightforward method to optimize yield and purity, facilitating industrial application. [ABSTRACT FROM AUTHOR]

The synthesis of enantiomerically pure tertiary alcohols is an important issue in organic synthesis of a range of pharmaceuticals including molecules such as the anti‐HIV drug Efavirenz. A conceptually elegant approach to such enantiomers is the dynamic kinetic resolution of racemic tertiary alcohols, which, however, requires efficient racemization strategies. The racemization of tertiary alcohols is particularly challenging due to various side reactions that can occur because of their high tendency for elimination reactions. In the last few years, several complementary catalytic concepts for racemization of tertiary alcohols have been developed, characterized by efficient racemization and suppression of unwanted side‐reactions. Besides resins bearing sulfonic acid moieties and a combination of boronic acid and oxalic acid as heterogeneous and homogeneous Brønsted‐acids, respectively, immobilized oxovanadium and piperidine turned out to be useful catalysts. The latter two catalysts, which have already been applied to different types of substrates, also have proven good compatibility with lipase, thus leading to the first two examples of chemoenzymatic dynamic kinetic resolution of tertiary alcohols. In this review, the difficulties in racemizing tertiary alcohols are specifically described, and the recently developed complementary concepts to overcome these hurdles are summarized. [ABSTRACT FROM AUTHOR]

Alkyne cycloisomerization of 2,7,10,15-tetra(ortho-alkynylphenyl)benzo[g,p]chrysene containing bulky 4-alkoxy-2,6-dimethylphenyl groups at the alkyne terminals selectively proceeded at the sterically crowded bay-region. The obtained double helicene adopts a distorted structure with a high racemization barrier due to the intramolecular steric repulsion. [ABSTRACT FROM AUTHOR]

The CPAPhosAuCl bifunctional complexes catalyse the enantioselective tandem cycloisomerization‐nucleophilic addition reactions between 2‐alkynylenones and naphthols, where naphthols behave mainly as O‐nucleophiles. The inherent acidity of the catalysts induces then the isomerization of the O‐addition‐ into the C‐addition products with concomitant decrease of their enantiomeric excesses. In depth mechanistic studies have provided insights into these processes. Subsequently, the undesired racemization pathways could be suppressed by using substituted naphthols as nucleophiles, which delivered a large series of chiral bicyclic furanes in high enantioselectivities. [ABSTRACT FROM AUTHOR]

Objective: Synthetic lipophilic constructs (Function–Spacer–Lipids, FSLs) are excellent tools for modification of cell surface with almost any molecular fragment. The aim of this research is synthesis of FSLs containing both glycan and fluorescent tag introduced in the structure of the construct independently to each other. Such compounds allow to avoid treatment with fluorescently labeled antibodies prior to visualization of inserted glycans by confocal microscopy thus opening the wide range of possibilities for studying biological processes involving these glycans. Methods: Two FSLs containing same glycan, A (type 2) tetrasaccharide, and spacerlipid block, CMG (carboxymethylglycine) spacer-arm and DOPE (dioleoylphosphatidylethanolamine) lipid, and various fluorescent tags, fluoresceine and sulfo-Cyanine-3, were synthesized. Derivatives of α- or ε-azido lysine were used as central blocks, to which all other fragments were attached. Two various approaches differing in the order of introduction of components were employed. Conjugation via CuAAC reaction was used in both synthetic schemes. Results and Discussion: The first approach (the following order of attachment of components: glycan, then spacer-lipid, then fluorescent tag) allowed to obtain target FSL according to proposed synthetic plan. When the second approach was employed (the following order of attachment: fluorescent tag, then glycan, then spacer–lipid), side reaction of racemization of central lysine block was observed during conjugation of glycan part. To overcome this problem, synthetic sequence was changed: amino group in lysine unit was protected and glycan was introduced prior to fluorescent tag. This modification allowed to avoid undesired racemization. Conclusions: Two FSL constructs containing A (type 2) tetrasaccharide, CMG–DOPE spacer-lipid block, and fluorescent tag (fluoresceine or sulfo-Cyanine-3) were obtained. Independent manner of attachment of glycan and fluorophore allows to study interaction of glycan with carbohydrate binding proteins directly in the cell membrane. [ABSTRACT FROM AUTHOR]

This study aims to investigate the impact of four key factors, namely, temperature, water source, metal ion, and pH, on the stability of molecular chirality of dihydromyricetin (DMY) and proposed effective strategies for configuration protection. The findings reveal that temperatures exceeding 80°C could accelerate the racemization process of DMY, with a significant increase in racemization observed at 100°C. In addition, DMY exhibited heightened stability in ultrapure water as compared to various water sources, including pure water‐1, pure water‐2, mineral water, and running water. Notably, the presence of Fe2+ displayed an inhibitory effect on the racemization of DMY, whereas Mg2+, Ca2+, and Mn2+ showed a substantial promotional effect. Additionally, acidic conditions (pH < 5.0) were found to be protective for maintaining the stability of DMY, whereas alkaline conditions (pH > 9.0) were observed to be detrimental. Meanwhile, we first identified the presence of another pair of DMY isomers in this work. [ABSTRACT FROM AUTHOR]

A novel one‐pot deracemization method using a bifunctional chiral agent (BCA) is proposed for the first time to convert a racemate to the desired enantiomer. Specifically, chiral α, (α‐diphenyl‐2‐pyrrolidinemethanol) formed enantiospecific cocrystals with racemic dihydromyricetin, and used its own alkaline catalysis to catalyze the racemization between the (2R,3R)‐enantiomer and (2S,3S)‐enantiomer in solution, achieving a one‐pot spontaneous deracemization. This strategy was also successfully extended to the deracemization of three other racemic compound drugs: (R,S)‐carprofen, (R,S)‐indoprofen, and (R,S)‐indobufen. The one‐pot deracemization method based on the BCA strategy provides a feasible approach to address the incompatibility between cocrystallization and racemization reactions that are commonly encountered in the cocrystallization‐induced deracemization process and opens a new window to develop essential enantiomerically pure pharmaceutical products with atom economy. [ABSTRACT FROM AUTHOR]

A novel C–N axially chiral molecule composed of two tert-butyl-substituted benzo[b]phenoxazine (BPO) was synthesized via solvent-free reactions. The absolute configurations of the enantiomers were determined by X-ray single-crystal analysis. The enantiomers had a sufficiently high racemization barrier to ignore racemization at room temperature (149 ± 20 kJ mol−1), and the solutions exhibited dual circularly polarized emissions stemming from fluorescence and phosphorescence of ‖gCPL‖ = ca. 1 × 10−3. [ABSTRACT FROM AUTHOR]

4,4′‐Biazulene is a potentially attractive key component of an axially chiral biaryl compound, however, its structure and properties have not been clarified owing to the lack of its efficient synthesis. We report a breakthrough in the reliable synthesis of 4,4′‐biazulene, which is achieved by the access to azulen‐4‐ylboronic acid pinacol ester and 4‐iodoazulene as novel key synthetic intermediates for the Suzuki‐Miyaura cross‐coupling reaction. The X‐ray crystallographic analysis of 4,4′‐biazulene confirmed its axial chirality. The enantiomers of 4,4′‐biazulene were successfully resolved by HPLC on the chiral stationary phase column. The kinetic experiments and DFT calculations indicate that the racemization energy barrier of 4,4′‐biazulene is comparable to that of 1,1′‐binaphthyl. [ABSTRACT FROM AUTHOR]

Atropisomeric N-chloroamides were efficiently accessed by electrophilic halogenation of ortho-substituted secondary anilides. The stereodynamics of atropisomerism in these novel scaffolds was interrogated by detailed experimental and computational studies, revealing that racemization is correlated with amide isomerization. The stereoelectronic nature of the amide was shown to significantly influence racemization rates, with potentially important implications for other C-N atropisomeric scaffolds. [ABSTRACT FROM AUTHOR]

How Nature synthesizes enantiomerically pure substances from achiral or racemic resources remains a mystery. In this study, we aimed to emulate this natural phenomenon by constructing chiral tetrahedral cages through self‐assembly, achieved by condensing two achiral compounds–a trisamine and a trisaldehyde. The occurrence of intercomponent CH⋅⋅⋅π interactions among the phenyl building blocks within the cage frameworks results in twisted conformations, imparting planar chirality to the tetrahedrons. In instances where the trisaldehyde precursor features electron‐withdrawing ester side chains, we observed that the intermolecular CH⋅⋅⋅π forces are strong enough to prevent racemization. To attain enantioselective self‐assembly, a chiral amine was introduced during the imine formation process. The addition of three equivalents of chiral amino mediator to one equivalent of the achiral trisaldehyde precursor formed a trisimino intermediate. This chiral compound was subsequently combined with the achiral trisamino precursor, leading to an imine exchange reaction that releasing the chiral amino mediator and formation of the tetrahedral cage with an enantiomeric excess (ee) of up to 75 %, exclusively composed of achiral building blocks. This experimental observation aligns with theoretical calculations based on the free energies of related cage structures. Moreover, since the chiral amine was not consumed during the imine exchange cycle, it enabled the enantioselective self‐assembly of the tetrahedral cage for multiple cycles when new batches of the achiral trisaldehyde and trisamino precursors were successively added. [ABSTRACT FROM AUTHOR]

Boron‐based enantiomerism is fragile due to the inherent tendency of a dissociation of a ligand from tetra‐coordinate chiral boron complexes under formation of the achiral tri‐coordinate species. This review will present the different approaches in overcoming the inherent tendency of racemization in boron‐stereogenic compounds. When embedded in an environment of chiral ligands or substituents, configurationally stable boron stereogenic centers can form in a diastereoselective manner. Compounds incorporating boron as the exclusive stereogenic center are obtained by resolution of the racemic mixtures. The recently developed – much more efficient – methods of a catalytic, enantioselective creation of boron stereogenic compounds are highlighted in this review. Finally the chiroptical properties of enantiomerically pure boron complexes that makes them promising materials or devices are addressed. [ABSTRACT FROM AUTHOR]

6,10‐Dipropyl‐5,9‐diaza[5]‐ and ‐[6]helicene were synthesized by ortho,ortho' fusion of ortho‐teraryldicarboxamides. Key steps in the synthesis of the teraryls are azide formation with subsequent reduction and amidation followed by Suzuki cross couplings. The ortho fusions were achieved with phosphorus pentoxide and phosphoryl oxide. The total syntheses could be accomplished with 10 % and 3 %, respectively, in seven consecutive steps starting with meta‐dibromobenzene. The helicenes were investigated by UV/Vis and fluorescence spectroscopy and by quantum chemical calculation of, inter alia, the HOMO‐LUMO gaps. Racemization barriers of the helicenes were calculated, whereupon the optical resolution of 5,9‐diaza[6]helicene was attempted and carried out successfully; ECD spectra were measured of its enantiomers. [ABSTRACT FROM AUTHOR]

A multi‐resonance (MR) fluorophore exhibiting circularly polarized luminescence (CPL) holds a significant promise for enhancing the utility of organic light‐emitting devices. To meet this demand, we have devised molecular dyads having azaoxaborin MR emitters based on homochiral (R)‐ and (S)‐1,1′‐bi‐2‐naphthol. The synthesized 12,12′‐di‐tert‐butyl‐9,9′‐bi(8,8′‐dioxa‐4b,4′b‐diaza‐14b,14′b‐diborafluorantheno[1,2,3‐de]tetracene) products (TBNBOCz) exhibit strong blue fluorescence, with a remarkable 100% fluorescence quantum yield and an extremely narrow full width at half‐maximum of 22 nm. However, unexpectedly, TBNBOCz exhibits negligible electric circular dichroism and CPL activities. Chiroptical investigations into the reaction precursors reveals an occurrence of racemization in the borylation step. This result emphasizes the importance of understanding synthetic processes and their impact on the chiroptical properties. [ABSTRACT FROM AUTHOR]

It is crucial to regulate N-methyl-D-aspartate (NMDA) function bivalently depending on the central nervous system (CNS) conditions. CNS disorders with NMDA hyperfunction are involved in the pathogenesis of neurotoxic and/or neurodegenerative disorders with elevated D-serine, one of the NMDA receptor co-agonists. On the contrary, NMDA-enhancing agents have been demonstrated to improve psychotic symptoms and cognition in CNS disorders with NMDA hypofunction. Serine racemase (SR), the enzyme regulating both D- and L-serine levels through both racemization (catalysis from L-serine to D-serine) and β-elimination (degradation of both D- and L-serine), emerges as a promising target for bidirectional regulation of NMDA function. In this study, we explored using dimethyl malonate (DMM), a pro-drug of the SR inhibitor malonate, to modulate NMDA activity in C57BL/6J male mice via intravenous administration. Unexpectedly, 400 mg/kg DMM significantly elevated, rather than decreased (as a racemization inhibitor), D-serine levels in the cerebral cortex and plasma. This outcome prompted us to investigate the regulatory effects of dodecagalloyl-α-D-xylose (α12G), a synthesized tannic acid analog, on SR activity. Our findings showed that α12G enhanced the racemization activity of human SR by about 8-fold. The simulated and fluorescent assay of binding affinity suggested a noncooperative binding close to the catalytic residues, Lys56 and Ser84. Moreover, α12G treatment can improve behaviors associated with major CNS disorders with NMDA hypofunction including hyperactivity, prepulse inhibition deficit, and memory impairment in animal models of positive symptoms and cognitive impairment of psychosis. In sum, our findings suggested α12G is a potential therapeutic for treating CNS disorders with NMDA hypofunction. [ABSTRACT FROM AUTHOR]

A desilylation process of optically active silyl‐substituted gem‐difluorocyclopropanes with tetrabutylammonium fluoride (TBAF) showed a substantial reduction of enantiopurity of the resultant gem‐difluorocyclopropanes even at ambient temperatures. The electron‐withdrawing aryl substituent at the 3‐position in the 1‐silyl‐2,2‐difluorocyclopropane system accelerated the racemization, indicating a correlation with the stability of the anionic intermediates. The plausible racemization pathway through homolytic cleavage of the distal bond in gem‐difluorocyclopropane is inconsistent with the experimental results because the high energy of >34 kcal/mol is required for generating the open‐shell 2,2‐difluoropropane‐1,3‐diyl skeleton. The DFT studies using the anionic 2,2‐difluoromethyl‐3‐phenylcyclopropanylide intermediate supported the alternative isomerization pathway through the intramolecular migration of hydrogen and the resultant thermodynamically stable 2,2‐difluoromethyl‐1‐phenylcyclopropanylide anion could facilitate the racemization process at the stereocenter. Although the transition state indicated considerable activation energies, the high frequency of imaginary vibration should correlate with a barrier of a very narrow width enabling quantum tunneling under the H‐migration step. The observed isotope effect is compatible with the proposed mechanism through the intramolecular H‐migration. [ABSTRACT FROM AUTHOR]

The first reliable observation of desolvation- and temperature-induced solid-phase racemization of the entire tris-chelates complex is reported. The capability of π–π stacking interactions to prevent such processes was revealed for the first time. [ABSTRACT FROM AUTHOR]

A novel approach has been developed for the efficient synthesis of the unsymmetrical (2-aminopyrrolidin-1-yl)carboxamidine alkaloidal core found in cernumidine (1) and its analogs (20a, 20c, 20f, 20i–o). The key transformation in this process involves the utilization of the Curtius rearrangement, which plays a pivotal role in constructing the aminal moiety. One of the major challenges encountered during this synthesis was the instability of the free aminal core intermediate. Furthermore, a noteworthy observation during the synthesis was the racemization process that occurred during the isocyanate trapping by organometallic reagents. Detailed DFT calculations shed light on this phenomenon, revealing a neighboring coordination-induced mechanism. The resulting compounds were subjected to evaluation for their anti-inflammatory properties using lipopolysaccharide-stimulated human THP1 cells. Notably, compounds featuring the guanidine moiety and electron-donating groups exhibited significant anti-inflammatory activity. These findings suggest that these compounds hold promise as potential candidates for further development as anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

We report a unique category of π‐extended diaza[7]helicenes with double negative curvatures. This is achieved by two‐fold regioselective heptagonal cyclization of the oligoarylene‐carbazole precursors through either intramolecular C−H arylation or Scholl reaction. The fusion of two heptagonal rings in the helical skeleton dramatically increases the intramolecular strain and forces the two terminal carbazole moieties to stack in a compressed fashion. The presence of the deformable negatively curved heptagonal rings endows the resulting diaza[7]helicenes with dynamic chiral skeletons, aggregation‐induced emission feature and relatively low racemization barrier of ca. 25.6 kcal mol−1. Further π‐extension on the carbazole moieties subsequently leads to a more sophisticated C2‐symmetric homochiral triple helicene. Notably, these π‐extended diaza[7]helicenes show structure‐dependent stacking upon crystallization, switching from heterochiral packing to intra‐layer homochiral stacking. Interestingly, the C2‐symmetric triple helicene molecules spontaneously resolve into a homochiral lamellar structure with 31 helix symmetry. Upon ultrasonication in a nonsolvent, the crystals can be readily exfoliated into large‐area ultrathin nanosheets with height of ca. 4.4 nm corresponding to two layers of stacked triple helicene molecules and relatively thicker nanosheets constituted by even‐numbered molecular lamellae. Moreover, regular hexagonal thin platelets with size larger than 30 μm can be readily fabricated by flash aggregation. [ABSTRACT FROM AUTHOR]

This paper presents an efficient one-pot approach for synthesizing hydroxylated 1,3-dithiane-pyrazolone hybrids. The process involves a reaction between pyrazolone derivatives, carbon disulfide, and epichlorohydrin (ECH). The structures of the produced 1,3-dithian-pyrazolone hybrids are determined based on their IR, 1H NMR, 13C NMR, and Mass spectroscopic data. Analysis of the 1H NMR spectra of compounds 4b and 4d revealed first-order splitting of the methylene hydrogens of the 1,3-dithian moiety, indicating that the OH group occupies an axial position in the preferred conformation of these derivatives. Despite the use of optically pure ECH as a starting material, racemization of products occurs during the reaction. The proposed reaction mechanism provides a rational explanation for this observation. [ABSTRACT FROM AUTHOR]

Serine palmitoyltransferase (SPT) catalyzes the pyridoxal-50-phosphate (PLP)-dependent decarboxylative condensation of Lserine and palmitoyl-CoA to form 3-ketodihydrosphingosine (KDS). Although SPT was shown to synthesize corresponding products from amino acids other than L-serine, it is still arguable whether SPT catalyzes the reaction with D-serine, which is a question of biological importance. Using high substrate and enzyme concentrations, KDS was detected after the incubation of SPT from Sphingobacterium multivorum with D-serine and palmitoyl-CoA. Furthermore, the KDS comprised equal amounts of 2S and 2R isomers. ¹H-NMR study showed a slow hydrogen-deuterium exchange at Cα of serine mediated by SPT. We further confirmed that SPT catalyzed the racemization of serine. The rate of the KDS formation from D-serine was comparable to those for the α-hydrogen exchange and the racemization reaction. The structure of the D-serine-soaked crystal (1.65 Å resolution) showed a distinct electron density of the PLP-L-serine aldimine, interpreted as the racemized product trapped in the active site. The structure of the α-methyl-Dserine-soaked crystal (1.70 Å resolution) showed the PLP-α-methyl-D-serine aldimine, mimicking the D-serine-SPT complex prior to racemization. Based on these enzymological and structural analyses, the synthesis of KDS from D-serine was explained as the result of the slow racemization to L-serine, followed by the reaction with palmitoyl-CoA, and SPT would not catalyze the direct condensation between D-serine and palmitoyl-CoA. It was also shown that the S. multivorum SPT catalyzed the racemization of the product KDS, which would explain the presence of (2R)-KDS in the reaction products. [ABSTRACT FROM AUTHOR]

8,8'-dimethyl-1,1'-bi-2-naphthol (7) was synthesized by oxidative dimerization of 8-methyl-2-naphthol (6). Camphorsulfonyl chloride was used as a chiral-resolving agent, followed by the synthesis of chiral dimethyl dinaphthofuran 3 by a dehydration reaction between two hydroxy groups without loss of optical purity. The racemization barrier and optical properties of the chiral compound 3 were scrutinized. [ABSTRACT FROM AUTHOR]

Lipase-catalyzed organic reactions have been widely practiced in the past three decades. Especially interesting are insoluble/immobilized forms due to providing a possibility of facile use and recyclability, thus reducing process costs, and making the procedure more environmentally friendly. Carbon-based supports have been extensively exploited for this purpose, because of neutral and biodegradable nature and thermal and chemical stability. Their high specific surface area, characteristic surface morphology and lower mass transfer resistances play a vital role in the performance of the attached enzyme. This review paper presents an overview of the main aspects of lipase immobilized on multi-walled carbon nanotubes (MWCNTs). Moreover, different immobilization strategies to achieve a biocatalyst with improved performances are discussed. Furthermore, as lipases are considered to have high commercial worth for synthesis of valuable organic molecules, the second part of the paper is dedicated to the overview of the most important industrial sectors in which these nanobiocatalysts have been used. In specific, applications in biodiesel production, flavour ester synthesis and racemization are summarize

A simple and rapid synthesis of (S)‐pyroglutamic acid was developed by the thermal cyclodehydration of (S)‐glutamic acid under solvent‐free conditions, with continuous swirling during heating (220°C) to ensure homogeneity of the melt. The reaction proceeds until the bubbles disappear, not exceeding 5 min. The heating immediately ceases, then cooling the reaction vessel to prevent degradation and racemization. (S)‐pyroglutamic acid is obtained in 70% yield, and the enantiomeric ratio is 97:3. The same reaction under microwave heating in an aqueous solution afforded a low yield of racemic product. [ABSTRACT FROM AUTHOR]

A highly enantioselective biocatalytic dynamic kinetic resolution (DKR) of 2‐(quinoline‐8‐yl) 3‐methylbenzaldehydes and 1‐naphthaldehydes is described. The reaction proceeds by atroposelective carbonyl reduction catalyzed by commercial ketoreductases (KREDs), generally reaching high conversions and excellent enantiomeric excesses. Both atropoisomers of the final alcohols can be obtained by a proper selection of the biocatalyst. The DKR strategy relies in the racemization of the stereogenic axis that takes place thanks to a transient Lewis acid‐base interaction (LABI) between the nitrogen in the quinoline and the carbonyl group. [ABSTRACT FROM AUTHOR]

The unique dynamic configuration of an enantioselective chiral‐at‐metal catalyst based on Rh(III) and a non‐chiral tetradentate ligand is described and resolved. At room temperature, the catalyst undergoes a dynamic configuration process leading to the formation of two interconvertible metal‐stereoisomers, remarkably without racemization. Density functional theory (DFT) calculations indicate that this metal‐isomerization proceeds via a concerted transition state, which features a trigonal bipyramidal geometry stabilized by the tetradentate ligand. Furthermore, the resolved enantiopure complex shows high catalytic enantioinduction in the Friedel‐Crafts reaction, achieving enantiomeric ratios as high as 99 : 1. [ABSTRACT FROM AUTHOR]

Triboelectrification necessitates a frictional interaction between two materials, and their contact electrification is characteristically based on the polarity variance in the triboelectric series. Utilizing this fundamental advantage of the triboelectric phenomenon, different materials can be identified according to their contact electrification capability. Herein, an in‐depth analysis of the amino acids present in the stratum corneum of human skin is performed and these are quantified regarding triboelectric polarization. The principal focus of this study lies in analyzing and identifying the amino acids present in copious amounts in the stratum corneum to explain their positive behavior during the contact electrification process. Thus, an augmented triboelectric series of amino acids with quantified triboelectric charging polarity by scrutinizing the transfer charge, work function, and atomic percentage is presented. Furthermore, the chirality of aspartic acid as it is most susceptible to racemization with clear consequences on the human skin is detected. The study is expected to accelerate research exploiting triboelectrification and provide valuable information on the surface properties and biological activities of these important biomolecules. [ABSTRACT FROM AUTHOR]

We herein describe the synthesis of a new class of axially chiral aza/boracyclophanes (BDN1, BXN1, BDB1 and BXB1) using binaphthyls as chiral building blocks and the main‐group (B/N) chemistry with tunable electronic effects. All macrocycles substituted with triarylamine donors or triarylborane acceptors are strongly luminescent. These macrocycles showed two distinct meta and para π‐conjugation pathways, leading to the formation of quasi figure‐of‐eight and square‐shaped conformations. Interestingly, comparison of such structural models revealed that the former type of macrocycles BXN1 and BXB1 gave higher racemization barriers relative to the other ones. The results reported here may provide a new approach to engineer the optical stability of π‐conjugated chiral macrocycles by controlling π‐substitution patterns. The ring constraints induced by macrocyclization were also demonstrated to contribute to the configurational persistence as compared with the open‐chain analogues p‐BTT and m‐BTT. [ABSTRACT FROM AUTHOR]

Axially chiral open‐chained olefins are an underexplored class of atropisomers, whose enantioselective synthesis represents a daunting challenge due to their relatively low racemization barrier. We herein report rhodium(I)‐catalyzed hydroarylative cyclization of 1,6‐diynes with three distinct classes of arenes, enabling highly enantioselective synthesis of a broad range of axially chiral 1,3‐dienes that are conformationally labile (ΔG≠(rac)=26.6–28.0 kcal/mol). The coupling reactions in each category proceeded with excellent enantioselectivity, regioselectivity, and Z/E selectivity under mild reaction conditions. Computational studies of the coupling of quinoline N‐oxide system reveal that the reaction proceeds via initial oxidative cyclization of the 1,6‐diyne to give a rhodacyclic intermediate, followed by σ‐bond metathesis between the arene C−H bond and the Rh−C(vinyl) bond, with subsequent C−C reductive elimination being enantio‐determining and turnover‐limiting. The DFT‐established mechanism is consistent with the experimental studies. The coupled products of quinoline N‐oxides undergo facile visible light‐induced intramolecular oxygen‐atom transfer, affording chiral epoxides with complete axial‐to‐central chirality transfer. [ABSTRACT FROM AUTHOR]

Introduction: Age estimation plays a crucial role in forensic dentistry, particularly in cases involving adults. This abstract highlights the challenges of age estimation among adults, emphasizing the ethical concerns when dealing with living individuals. Aim: The primary aim of this review is to discuss various age estimation methods applicable to adults in forensic dentistry. It evaluates the reliability and suitability of these methods based on legal questions and specific populations. Materials and Methods: The review explores several age estimation techniques, including Gustafson’s method, dentin translucency, pulp-tooth ratio, cementum annulation, attrition, amino acid racemization, and radiocarbon analysis of dentition. It also underscores the histological and biochemical approaches while acknowledging the ethical challenges associated with extracting tooth specimens from living individuals. The collaboration between forensic dentistry investigators and statistics experts is essential for achieving accurate and population-specific calculations. Conclusion: In forensic dentistry, the objective of age estimation is not merely to provide an exact age but to determine a scientifically relevant age range. By employing various age estimation methods and presenting their results to the legal system, investigators can offer valuable insights into the age of individuals, considering the strengths and limitations of each approach. This collaborative effort ensures that the age estimation process is accurate and context-specific. [ABSTRACT FROM AUTHOR]

Axially chiral diaryl ethers, a distinguished class of atropisomers possessing unique dual C−O axis, hold immense potential for diverse research domains. In contrast to the catalytic enantioselective synthesis of conventional single axis bearing atropisomers, the atroposelective synthesis of axially chiral ethers containing flexible C−O axis remains a significant challenge. Herein, we demonstrate the first N‐heterocyclic carbene (NHC)‐catalyzed synthesis of axially chiral diaryl ethers via atroposelective esterification of dialdehyde‐containing diaryl ethers. Mechanistically, the reaction proceeds via NHC‐catalyzed desymmetrization strategy to afford the corresponding axially chiral diaryl ether atropisomers in good yields and high enantioselectivities under mild conditions. The derivatization of the synthesized product expands the utility of present strategy via access to a library of C−O axially chiral compounds. The temperature dependency and preliminary investigations on the racemization barrier of C−O bonds are also presented. [ABSTRACT FROM AUTHOR]

Chirality is a fundamental characteristic of nature. Expanded porphyrinoids and their analogues offer an attractive platform for delving into the intricacies of chirality. Expanded porphyrinoids comprise pyrrolic macrocycles and related heterocyclic systems. As a class, expanded porphyrinoids are widely recognized for their flexible structural features, nontrivial coordination capabilities, and intriguing optical and electronic properties. With limited exceptions, their inherent conformational flexibility coupled with a low racemization barrier allows for the facile interchange between enantiomers. As a result, achieving the effective chiral resolution of individual enantiomers and the subsequent exploration of their chiroptical properties represents a significant challenge. This review summarizes strategies used to realize the chiral resolution of expanded porphyrinoids and the understanding of intrinsic chiroptical properties that has emerged from these separation efforts. It is our hope that this review will serve not only to codify our current understanding of chiral expanded porphyrinoids, but also inspire advances in the generalized area of chiral functional materials. [ABSTRACT FROM AUTHOR]

N-N atropisomers represent a useful class of compounds that has recently received important attention from many research groups. This article presents an in-depth analysis of the energy barrier needed for the racemization process of atropoisomeric hydrazides, combining an experimental and computational approach. The focus is on examining how electronic and steric factors impact the racemization process. The results obtained indicate that the barrier observed during the racemization process mainly arises from an increase in the p-orbital character of the nitrogen atoms. [ABSTRACT FROM AUTHOR]

A novel axially chiral all-hydrocarbon cyclo[7] (1,3-(4,6-dimethyl)benzene (CDMB-7) was designed and synthesized using atroposelective[2 + 5] cyclization through Suzuki–Miyaura coupling. CDMB-7 adopts an irregular bowl-like shape with C2 symmetry and exhibits two diastereoisomers in its crystallographic structure. The conformational isomers of CDMB-7 racemates remain stable at high temperatures (393 K). High-performance liquid chromatography (HPLC) confirmed that a single chiral isomer will spontaneously undergo racemization within 30 min at room temperature. This finding opens up possibilities for achieving adaptive chirality in all-hydrocarbon cyclo[7] m-benzene macrocycles.