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Strigolactones (SLs), plant-derived apocarotenoids, serve dual roles as phytohormones and rhizosphere signaling molecules. While exogenous administration of SLs to plants aids in studying their functions, the metabolic destiny of these administered SLs remains poorly elucidated. Our previous research demonstrated that among synthetic SL GR24 stereoisomers administered to cowpea (Vigna unguiculata), 2′- epi -GR24 undergoes selective reduction at the C-3′,4′ double bond in its D-ring. In this investigation, we isolated proteins from cowpea roots based on SL reducing activity and identified 12-oxophytodienoate reductase 3 homologs (VuOPR3s) as contributors to this reduction. Enzymatic assays conducted with recombinant proteins revealed that VuOPR3s exhibited a preference for reducing activity toward 2′ S -configured SLs, including 2′- epi -GR24. This specificity for 2′ S -configured SLs was congruent with that observed for orobanchol produced by cowpea and its stereoisomers. These findings suggest that exogenously administered SLs undergo enzymatic stereoselective reduction, underscoring the importance of considering stereospecificity when interpreting data obtained from SL usage. [ABSTRACT FROM AUTHOR]

This review introduces the synthetic organic chemical value of α‐bromocarbonyl compounds with tertiary carbons. This α‐bromocarbonyl compound with a tertiary carbon has been used primarily only as a radical initiator in atom transfer radical polymerization (ATRP) reactions. However, with the recent development of photo‐radical reactions (around 2010), research on the use of α‐bromocarbonyl compounds as tertiary alkyl radical precursors became popular (around 2012). As more examples were reported, α‐bromocarbonyl compounds were studied not only as radicals but also for their applications in organometallic and ionic reactions. That is, α‐bromocarbonyl compounds act as nucleophiles as well as electrophiles. The carbonyl group of α‐bromocarbonyl compounds is also attractive because it allows the skeleton to be converted after the reaction, and it is being applied to total synthesis. In our survey until 2022, α‐bromocarbonyl compounds can be used to perform a full range of reactions necessary for organic synthesis, including multi‐component reactions, cross‐coupling, substitution, cyclization, rearrangement, stereospecific reactions, asymmetric reactions. α‐Bromocarbonyl compounds have created a new trend in tertiary alkylation, which until then had limited reaction patterns in organic synthesis. This review focuses on how α‐bromocarbonyl compounds can be used in synthetic organic chemistry. [ABSTRACT FROM AUTHOR]

A substituted bishomocubane structure colloquially known as a Thiele cage was previously observed to undergo an alkyl-extended pinacol-type rearrangement, wherein 1,2-aryl migration and ketone formation occurred together with (or at least in close succession to) opening of a strained cyclobutane bond. While there was some indication that the rearrangement reaction might proceed via a stepwise process involving a sequence of carbocation intermediates, previous studies did not uncover any direct evidence for the formation of carbocations, and did not fully explain the regio- and stereospecificity of the reaction. Here we describe the isolation and detailed characterization of a second rearrangement product formed under the pinacol reaction conditions, the existence of which implicates the formation of discrete carbocation intermediates along the reaction pathway. Observation of this new product also finally explains the fate of any Thiele cage material that is converted to a carbocation, but which is not geometrically predisposed to react through a facile 1,2-aryl migration. As such, our findings resolve previous questions surrounding the origin of regio- and stereospecificity in the alkyl-extended pinacol rearrangement. [ABSTRACT FROM AUTHOR]

The BH3‐mediated reduction of P‐stereogenic hydroxyalkylphosphine oxides was investigated by Density Functional Theory calculations. By combining theoretical approaches with experimental observations, we explored two mechanisms that account for its stereospecificity, implying an inversion of the configuration at the phosphorus atom. One mechanism proceeds through a cyclic intermediate in which the coordination of borane to the oxygen atoms lowers the BH3.THF‐attack barrier. However, the free energy barrier for this combined process is too high for a reaction feasible at room temperature. The calculations rather support a second mechanism that proceeds through from the same cyclic intermediate and the in‐situ formation of BH4− as reducing agent. [ABSTRACT FROM AUTHOR]

Enzymatic cleavage of C-F bonds in per-and polyfluoroalkyl substances (PFAS) is largely unknown but avidly sought to promote systems biology for PFAS bioremediation. Here, we report the reductive defluorination of α, β-unsaturated per-and polyfluorocarboxylic acids by Acetobacterium spp. The microbial defluorination products were structurally confirmed and showed regiospecificity and stereospecificity, consistent with their formation by enzymatic reactions. A comparison of defluorination activities among several Acetobacterium species indicated that a functional fluoride exporter was required for the detoxification of the released fluoride. Results from both in vivo inhibition tests and in silico enzyme modeling suggested the involvement of enzymes of the flavin-based electron-bifurcating caffeate reduction pathway [caffeoyl-CoA reductase (CarABCDE)] in the reductive defluorination. This is a report on specific microorganisms carrying out enzymatic reductive defluorination of PFAS, which could be linked to electron-bifurcating reductases that are environmentally widespread. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Treponema is a Gram‐negative anaerobic bacterium, among which the pathogenic Treponema can cause various diseases, such as venereal syphilis (Treponema pallidum), yaws (Treponema carateum), and oral diseases (Treponema denticola and Treponema medium). Although different from conventional lipopolysaccharides, the extracellular glycoconjugate of Treponema may still be a potential antigen and provide a candidate for vaccine development. Hence, we completed the first chemical synthesis of Treponema medium ATCC 700293 tetrasaccharide precursor containing L‐ornithine (L‐Orn) and D‐aspartic acid (D‐Asp) derivatives. The efficiency of non‐reducing end disaccharide formation has been improved by optimizing the assembly of the protecting groups in the donors and acceptors. Our [3+1] glycosylation strategy attempted to reduce the length of the acceptor to increase the nucleophilicity of the hydroxyl group, thereby improving the efficiency of synthesizing the target tetrasaccharide. The L‐Orn derivative was introduced at the final stage due to its influence on the glycosylation stereospecificity and efficiency. Therefore, the successful introduction of two amino acid derivatives and the synthesis of a tetrasaccharide precursor with complex functional‐group modifications have provided valuable insights for synthesizing other complex bacterial glycans. [ABSTRACT FROM AUTHOR]

2-Keto-3-deoxy-galactonate (KDGal) serves as a pivotal metabolic intermediate within both the fungal d-galacturonate pathway, which is integral to pectin catabolism, and the bacterial DeLey-Doudoroff pathway for d-galactose catabolism. The presence of KDGal enantiomers, l-KDGal and d-KDGal, varies across these pathways. Fungal pathways generate l-KDGal through the reduction and dehydration of d-galacturonate, whereas bacterial pathways produce d-KDGal through the oxidation and dehydration of d-galactose. Two distinct catabolic routes further metabolize KDGal: a nonphosphorolytic pathway that employs aldolase and a phosphorolytic pathway involving kinase and aldolase. Recent findings have revealed that l-KDGal, identified in the bacterial catabolism of 3,6-anhydro-l-galactose, a major component of red seaweeds, is also catabolized by Escherichia coli, which is traditionally known to be catabolized by specific fungal species, such as Trichoderma reesei. Furthermore, the potential industrial applications of KDGal and its derivatives, such as pyruvate and d- and l-glyceraldehyde, are underscored by their significant biological functions. This review comprehensively outlines the catabolism of l-KDGal and d-KDGal across different biological systems, highlights stereospecific methods for discriminating between enantiomers, and explores industrial application prospects for producing KDGal enantiomers. Key points: • KDGal is a metabolic intermediate in fungal and bacterial pathways • Stereospecific enzymes can be used to identify the enantiomeric nature of KDGal • KDGal can be used to induce pectin catabolism or produce functional materials [ABSTRACT FROM AUTHOR]

Derived from the denitrifying bacterium Aromatoleum aromaticum EbN1 (Azoarcus sp.), the enzyme S-1-(4-hydroxyphenyl)-ethanol dehydrogenase (S-HPED) belongs to the short-chain dehydrogenase/reductase family. Using research techniques like UV-Vis spectroscopy, dynamic light scattering, thermal-shift assay and HPLC, we investigated the catalytic and structural stability of S-HPED over a wide temperature range and within the pH range of 5.5 to 9.0 under storage and reaction conditions. The relationship between aggregation and inactivation of the enzyme in various pH environments was also examined and interpreted. At pH 9.0, where the enzyme exhibited no aggregation, we characterized thermally induced enzyme inactivation. Through isothermal and multitemperature analysis of inactivation data, we identified and confirmed the first-order inactivation mechanism under these pH conditions and determined the kinetic parameters of the inactivation process. Additionally, we report the positive impact of glucose as an enzyme stabilizer, which slows down the dynamics of S-HPED inactivation over a wide range of pH and temperature and limits enzyme aggregation. Besides characterizing the stability of S-HPED, the enzyme's catalytic activity and high stereospecificity for 10 prochiral carbonyl compounds were positively verified, thus expanding the spectrum of substrates reduced by S-HPED. Our research contributes to advancing knowledge about the biocatalytic potential of this catalyst. [ABSTRACT FROM AUTHOR]

The Zweifel olefination is a highly efficient and versatile method for constructing carbon-carbon double bonds in organic synthesis. It avoids the use of transition metals and has been applied in natural product synthesis and drug discovery. Recent progress in the field includes the use of new organometallic species, electrochemical and photocatalyzed reactions, and exploration of milder reaction conditions. However, further research is needed to develop less functional-group-sensitive reagents and investigate new strategies for generating alkenyl boron complexes. [Extracted from the article]

This article presents a new method for synthesizing α-quaternary carbaldehydes through the chemoselective House-Meinwald rearrangement of trisubstituted epoxides. The authors used Brønsted acids as catalysts and identified optimal reaction conditions. The method allows for the synthesis of various carbaldehydes and has been validated for stereospecific reactions. The authors suggest that this method could be useful in the total synthesis of natural products. [Extracted from the article]

A molybdenum‐catalyzed approach for intermolecular C−N coupling that produces aryl‐ and heteroaryl amines has been developed under microwave irradiation. The formation of C−N bonds with boronic acids and nitroaromatics using readily available catalysts remains a challenge. The method we developed employs a combination of readily available sodium molybdate dihydrate as a catalyst and tri‐n‐butyl phosphine as an inexpensive reductant to achieve reductive intermolecular coupling of nitroarenes with boronic acids. This approach has shown its versatility in facilitating the formation of Csp2−N bonds from aryl‐boronic acids as well as Csp3−N bonds from alkyl‐boronic acids. In addition, this reaction shows stereospecificity when Csp3−N bonds are formed. An array of boronic acids underwent C−N coupling with nitro arene providing the desired products in good yields [ABSTRACT FROM AUTHOR]

Menispermaceae species, as early‐diverging eudicots, can synthesize valuable benzylisoquinoline alkaloids (BIAs) like bisbenzylisoquinoline alkaloids (bisBIAs) and sinomenines with a wide range of structural diversity. However, the evolutionary mechanisms responsible for their chemo‐diversity are not well understood. Here, a chromosome‐level genome assembly of Menispermum dauricum is presented and demonstrated the occurrence of two whole genome duplication (WGD) events that are shared by Ranunculales and specific to Menispermum, providing a model for understanding chromosomal evolution in early‐diverging eudicots. The biosynthetic pathway for diverse BIAs in M. dauricum is reconstructed by analyzing the transcriptome and metabolome. Additionally, five catalytic enzymes – one norcoclaurine synthase (NCS) and four cytochrome P450 monooxygenases (CYP450s) – from M. dauricum are responsible for the formation of the skeleton, hydroxylated modification, and C‐O/C‐C phenol coupling of BIAs. Notably, a novel leaf‐specific MdCYP80G10 enzyme that catalyzes C2′‐C4a phenol coupling of (S)‐reticuline into sinoacutine, the enantiomer of morphinan compounds, with predictable stereospecificity is discovered. Moreover, it is found that Menispermum‐specific CYP80 gene expansion, as well as tissue‐specific expression, has driven BIA diversity in Menispermaceae as compared to other Ranunculales species. This study sheds light on WGD occurrences in early‐diverging eudicots and the evolution of diverse BIA biosynthesis. [ABSTRACT FROM AUTHOR]

Herein, we disclosed the asymmetric construction of an oxa‐quaternary stereocenter via an intramolecular oxa‐Michael (IOM) reaction in β‐substituted ortho‐hydroxymethyl chalcone by the formation of 1,1‐disubstituted‐1,3‐dihydroisobenzofuran using cinchona alkaloid‐based chiral amino‐squaramide catalyst. Both the (E‐ and Z)‐β‐substituted ortho‐hydroxymethyl chalcone provide (S)‐ and (R)‐enantiomers of the 1,1‐disubstituted‐1,3‐dihydroisobenzofuran with excellent stereospecificity. In general, excellent yields (up to 95 %) and enantioselectivity (up to 98 % ee) were obtained. Furthermore, the resulting 1,1‐disubstituted isobenzofuran or phthalan was converted to corresponding chiral 3,3‐disubstituted phthalides without losing the enantioselectivity. This methodology provides the core moiety of the (S)‐citalopram drug. [ABSTRACT FROM AUTHOR]

Whereas the conventional anti-dihalogenation of alkenes is a valuable synthetic tool with highly predictable stereospecificity, the restricted reaction mechanism makes it challenging to alter the diastereochemical course into the complementary syn-dihalogenation process. Only a few notable achievements were made recently by inverting one of the stereocenters after anti-addition using a carefully designed reagent system. Here, we report a conceptually distinctive strategy for the simultaneous double electrophilic activation of the two alkene carbons from the same side. Then, the resulting vicinal leaving groups can be displaced iteratively by nucleophilic halides to complete the syn-dihalogenation. For this purpose, thianthrenium dication is employed, and all possible combinations of chlorine and bromine are added onto internal alkenes successfully, particularly resulting in the syn-dibromination and the regiodivergent syn-bromochlorination. Restricted reaction mechanism of anti-dihalogenation of alkenes makes it challenging to alter the diastereochemical course into the complementary syn-dihalogenation process. Here, the authors report a conceptually distinctive strategy for the simultaneous double electrophilic activation of the two alkene carbons from the same side to realize syn-dihalogenation. [ABSTRACT FROM AUTHOR]

Cycloaddition reactions serve as exceptionally useful strategy to provide atom‐economical, efficient and practical access to complex molecules from simple starting materials. The [4+2]‐cycloaddition reaction allows for the stereospecific construction of six‐membered carbo‐/heterocycles. Cycloaddition reactions catalyzed by transition metals are potent methods for the rapid construction of highly functionalized molecular frameworks. This review article summarizes the different reports on transition‐metal catalyzed [4+2]‐cycloaddition reactions involving various transition metals such as Pd, Cu, Rh, Au, Fe, Ni, Sc, Sn, Hf, Ag, Mn, Dy, Co etc. for the straightforward construction of pharmaceutically active six‐membered heterocycles. An emphasis is laid on the mechanistic insights to highlight the unique application of novel processes of transition‐metals in these transformations to build intricate polycyclic structures. [ABSTRACT FROM AUTHOR]

Norcoclaurine synthase from Thalictrum flavum (TfNCS) demonstrated high stereospecificity and yield in catalyzing the Pictet-Spengler reaction of dopamine with chiral aldehydes, achieving kinetic resolution of aldehydes. However, the mechanism and the factors contributing to the stereoselectivity remain unclear. Herein, by using quantum chemical calculations, the mechanisms of TfNCS-catalyzed reactions of dopamine with both enantiomers of α-methyl-phenylacetaldehyde are studied. The calculations reveal a mechanism mirroring the reaction of natural substrates, for which the deprotonation of the C5−H of the cyclized intermediate is rate-limiting. The calculated overall barriers are 20.1 kcal mol-1 and 21.6 kcal mol-1 for the reactions of (R)- and (S)-α-methyl-phenylacetaldehyde, respectively. The M97 and L72 residues are proposed to be the key residues contributing to the stereospecificity. The obtained detailed information is helpful for designing new variants of TfNCS with extended substrate scope, and also advancing our understanding of TfNCS reactions for potential applications. Norcoclaurine synthase from Thalictrum flavum (TfNCS) has been demonstrated to display high stereospecificity and yield in catalyzing the Pictet-Spengler reaction of dopamine with chiral aldehydes, however, the mechanism and factors related to this high stereospecificity remain unclear. Here, the authors conduct quantum chemical calculations and reveal the rate-limiting step and differential energy barriers for the reactions of two enantiomers of α-methylphenylacetaldehyde, as well as key residues related to stereospecificity. [ABSTRACT FROM AUTHOR]

We present the first example of electrocatalytic three‐component annulation–iodosulfonylation of indole‐tethered 1,6‐enynes with arylsulfonyl hydrazides and KI for accessing various iodosulfonated pyrrolo[1,2‐a]indoles in moderate to excellent yields with high stereospecificity. This electrosynthesis opens new avenues for the construction of pyrrolo[1,2‐a]indoles skeleton with good functional group compatibility under environmentally benign condition. Based on the control experiments and cyclic voltammetry data, we suggested the plausible reaction mechanism which included anodic oxidation, homolysis of arylsulfonyl iodide, arylsulfonyl radical addition, 5‐exo‐dig cyclization, radical coupling or nucleophilic attack of iodide ions cascade. [ABSTRACT FROM AUTHOR]

N,N′-Disubstituted ureas and thioureas containing a 1,1,7-trimethylbicyclo[2.2.1]heptan-2-yl sub-stit-uent were synthesized in up to 99% yields by the reaction of exo-(R or S)-1,1,7-trimethylbicyclo[2.2.1]-heptan-2-amine with aromatic isocyanates and isothiocyanates with the goal of comprehensive estimation of enantiomeric stereospecificity of human soluble epoxide hydrolase (hsEH). The synthesized compounds are promising hsEH inhibitors. [ABSTRACT FROM AUTHOR]

A dimeric dipeptide mimetic based on the β-turn of the 4th loop of neurotrophin-3, bis-(N-monosuccinyl-L-asparaginyl-L-asparagine)hexamethylenediamide (GTS-301LL), was recently designed and synthesized by us. GTS-301, like the full-length neurotrophin, activated TrkC and TrkB receptors and exhibited neuroprotective activity on HT22 cells under oxidative stress conditions in the concentration range 10–5 – 10–12 M and antidepressant-like activity in the forced swimming test in mice (10 – 40 mg/kg, intraperitoneally). The stereospecificity of the pharmacological effects of GTS-301LL was revealed by synthesizing the LD, DL, and DD stereoisomers of GTS-301LL and studying their neuroprotective and antidepressant-like properties under the same conditions as for GTS-301LL. Both activities were found to disappear on going from the LL to the DL and DD stereoisomers and were retained on going to the LD stereoisomer. Thus, the stereospecificity of the neuroprotective and antidepressant-like activities of the dipeptide mimetic of neurotrophin-3 GTS-301LL at the N-terminal asparagine residue was proven, which indicated the key role of that amino-acid residue in the interaction with the receptor. [ABSTRACT FROM AUTHOR]

This article provides an overview of recent advancements in Friedel-Crafts alkylation reactions, specifically focusing on the use of different alkylating agents. It discusses the history and background of the reaction, as well as the use of alcohols, aldehydes, ketones, epoxides, cyclopropanes, and alkyl fluorides as alkylating agents. The article highlights the challenges and limitations of Friedel-Crafts alkylation and suggests future research directions. It also emphasizes the potential applications of this reaction in the synthesis of natural products and complex molecules. Overall, this article serves as a valuable resource for researchers in the field of organic synthesis. [Extracted from the article]

This article discusses the practical asymmetric synthesis of sulfoximines and sulfimides from sulfinamides. The authors highlight the importance of sulfur-containing functional groups in various fields and the relevance of chiral sulfoximines and sulfimides in agrochemicals and pharmaceuticals. They describe their own research in developing sulfur-selective alkylation and arylation reactions to achieve the desired transformations, and demonstrate the synthesis of various enantioenriched sulfoximines and sulfimides. The authors acknowledge the contributions of Prof. K. Maruoka and Dr. Y. Aota to this research. [Extracted from the article]

Reactions of chiral α‐bromoamides with AgF readily gave the corresponding 2‐fluorinated amide with retention of configuration. The mechanism and origin of the stereochemistry were rationalized using density functional theory calculations, which suggested a double‐inversion pathway via the formation of an aziridinone intermediate. The computed reaction pathway is consistent with the experimental results. In addition, the stereochemistry in base‐promoted trifluoromethylthiolation of α‐bromoamides using AgSCF3 was examined. The experimental results showed that the reaction proceeds through the generation of a neutral aziridinone intermediate, following the attack of a trifluoromethylthiolate anion at C‐3. The stereoselectivity of C‐3 attack on the aziridinone depended on the steric bulk of substitutes on the α‐position and nitrogen of the amide. The study results show the potential utility of AgF and AgSCF3 in the synthesis of chiral 2‐functionalized amide derivatives and provide mechanistic insights for nucleophilic substitution of 2‐bromoamides. [ABSTRACT FROM AUTHOR]

Reactions of chiral α‐bromoamides with AgF readily gave the corresponding 2‐fluorinated amide with retention of configuration. The mechanism and origin of the stereochemistry were rationalized using density functional theory calculations, which suggested a double‐inversion pathway via the formation of an aziridinone intermediate. The computed reaction pathway is consistent with the experimental results. In addition, the stereochemistry in base‐promoted trifluoromethylthiolation of α‐bromoamides using AgSCF3 was examined. The experimental results showed that the reaction proceeds through the generation of a neutral aziridinone intermediate, following the attack of a trifluoromethylthiolate anion at C‐3. The stereoselectivity of C‐3 attack on the aziridinone depended on the steric bulk of substitutes on the α‐position and nitrogen of the amide. The study results show the potential utility of AgF and AgSCF3 in the synthesis of chiral 2‐functionalized amide derivatives and provide mechanistic insights for nucleophilic substitution of 2‐bromoamides. [ABSTRACT FROM AUTHOR]

Vinyl ethers are valuable synthetic intermediates which are also found as natural products, including aflatoxins, rifamycins and plasmalogens. The latter are ubiquitous phospholipids in human cells and contain a vinyl ether moiety with specifically Z configuration. Although numerous methods are available for synthesis of vinyl ethers, there is a lack of methods for obtaining Z isomers of molecules of the type RCH=CHOR' that are applicable to plasmalogens. A variant of the Peterson reaction is described that generates such molecules with very high stereoselectivity (Z/E ratio: 99 : 1). (R,R)/(S,S)‐1‐alkoxy‐2‐hydroxyalkylsilanes were synthesized from 1‐trimethylsilylalkynes by a sequence of reduction with di‐isobutylaluminium hydride to a (Z)‐1‐trimethylsilylalkene, epoxidation of the alkene to a 2‐trimethylsilyl‐3‐substituted epoxide and regioselective, boron‐trifluoride catalyzed ring‐opening of the epoxide by reaction with an alcohol. Conversion of the (R,R)/(S,S)‐1‐alkoxy‐2‐hydroxyalkylsilanes to vinyl ethers (RCH=CHOR') was achieved under basic conditions as in a standard Peterson reaction. However, near exclusive formation of a Z vinyl ether was only achieved when the reaction was performed using potassium hydride in the non‐polar solvent α,α,α‐trifluorotoluene, more polar solvents giving increasing amounts of the E isomer. The sequence described embraces a variety of substituents and precursors, proceeds in overall high yield and is readily scalable. [ABSTRACT FROM AUTHOR]

On the base of structural and thermodynamic data using modern methods of quantum chemistry, a comparative theoretical study of the elementary acts of initiation and growth of a polymer chain during the polymerization of 1,3‐butadiene was carried out. Ziegler–Natta catalysts based on Nd(III) and Gd(III) were used as polymerization initiators. It was shown that the higher stereospecificity of the action of gadolinium catalytic complexes in comparison with neodymium complexes is due to the increased stability of the anti‐form of the π‐allylic terminal structure of the growing polymer chain, and the reduced activity is due to the higher activation energy of the processes of initiation and chain growth. [ABSTRACT FROM AUTHOR]

Loxoprofen sodium is a chiral drug with two chiral centers. In our previous work, we found that the elimination of its four isomers showed stereospecificity in rats, while how the stereospecific behavior occurred in vivo was unclear. To clarify this issue, each single isomer of loxoprofen sodium was prepared by a chiral semi‐preparative high‐performance liquid chromatography (HPLC) and then administered to rats. By analysis of each isomer in rat plasma utilizing an analytical chiral HPLC, it was discovered that the chiral inversion occurred only to its (2R)‐isomers, one from (1′S,2R)‐ to (1′S,2S)‐isomer and the other from (1′R,2R)‐ to (1′R,2S)‐isomer. The reduction of α‐substituted cyclopentanone occurred only to its (1′R)‐isomers, with (1′R,2R)‐isomer reduced to (2′S,1′R,2R)‐trans‐alcohol and (1′R,2S)‐ to (2′S,1′R,2S)‐trans‐alcohol. Interestingly, both the inversion and the reduction reaction occurred to its (1′R,2R)‐isomer due to the special stereo‐structure with both (2R)‐ and (1′R)‐configuration, and conversely, neither of them occurred to its (1′S,2S)‐isomer, which caused the significantly different elimination rate in vivo. These new findings were meaningful for evaluation of the safety and efficacy of chiral drugs. [ABSTRACT FROM AUTHOR]

A method of desymmetrization of geminal difluoroalkanes using frustrated Lewis pair (FLP) mediated monoselective C–F activation where a chiral sulfide is the Lewis base component is reported. The stereoselective reaction provides generally high yields of diastereomeric sulfonium salts with dr of up to 95:5. The distribution of diastereomers is found to be thermodynamically controlled via facile sulfide exchange. The use of enantiopure chiral sulfides allows for high stereospecificity in nucleophilic substitution reactions and the formation of stereoenriched products. [ABSTRACT FROM AUTHOR]

A novel metabolic pathway of 3,6-anhydro-l-galactose (l-AHG), the main sugar component in red macroalgae, was first discovered in the marine bacterium Vibrio sp. EJY3. l-AHG is converted to 2-keto-3-deoxy-galactonate (KDGal) in two metabolic steps. Here, we identified the enantiomeric nature of KDGal in the l-AHG catabolic pathway via stereospecific enzymatic reactions accompanying the biosynthesis of enantiopure l-KDGal and d-KDGal. Enantiopure l-KDGal and d-KDGal were synthesized by enzymatic reactions derived from the fungal galacturonate and bacterial oxidative galactose pathways, respectively. KDGal, which is involved in the l-AHG pathway, was also prepared. The results obtained from the reactions with an l-KDGal aldolase, specifically acting on l-KDGal, showed that KDGal in the l-AHG pathway exists in an l-enantiomeric form. Notably, we demonstrated the utilization of l-KDGal by Escherichia coli for the first time. E. coli cannot utilize l-KDGal as the sole carbon source. However, when a mixture of l-KDGal and d-galacturonate was used, E. coli utilized both. Our study suggests a stereoselective method to determine the absolute configuration of a compound. In addition, our results can be used to explore the novel l-KDGal catabolic pathway in E. coli and to construct an engineered microbial platform that assimilates l-AHG or l-KDGal as substrates. Key points: • Stereospecific enzyme reactions were used to identify enantiomeric nature of KDGal • KDGal in thel-AHG catabolic pathway exists in an l-enantiomeric form • E. coli can utilizel-KDGal as a carbon source when supplied withd-galacturonate [ABSTRACT FROM AUTHOR]

Enones are widely utilized linchpin functional groups in chemical synthesis and molecular biology. We herein report the direct conversion of boronic esters into enones using commercially available methoxyallene as a three‐carbon building block. Following boronate complex formation by reaction of the boronic ester with lithiated‐methoxyallene, protonation triggers a stereospecific 1,2‐migration before oxidation generates the enone. The protocol shows broad substrate scope and complete enantiospecificity is observed with chiral migrating groups. In addition, various electrophiles could be used to induce 1,2‐migration and give a much broader range of α‐functionalized enones. Finally, the methodology was applied to a 14‐step synthesis of the enone‐containing polyketide 10‐deoxymethynolide. [ABSTRACT FROM AUTHOR]

The reaction of pulegone with 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione as enophile gives two known epimers, 1-[(1R,4R)-4-methyl-2-oxo-1-(prop-1-en-2-yl)cyclohexyl]-4-phenyl-1,2,4-triazolidine-3,5-dione (RR isomer) and 1-[(1S,4R)-4-methyl-2-oxo-1-(prop-1-en-2-yl)cyclohexyl]-4-phenyl-1,2,4-triazolidine-3,5-dione (SR isomer). In addition, we isolated previously unknown 1-{2-[(4R)-4-methyl-6-oxocyclohex-1-en-1-yl]propan-2-yl}-4-phenyl-1,2,4-triazolidine-3,5-dione. According to the results of quantum chemical simulation, the isomeric products of hydrogen substitution in pulegone by the enophile are formed along three pathways. The SR isomer is formed via a concerted ene reaction. The other two channels involve approach of the enophile from the R side of pulegone and include two consecutive steps. The first step generates intermediate unsymmetrical cyclic aziridine cation, and elimination of proton from one of the geminal methyl groups of that intermediate yields the RR isomer with a terminal double bond. Proton elimination from methylene group of the pulegone fragment gives a cyclic compound with internal double bond. The ratio of the isomer with internal double bond and the RR isomer depends on the polarity of aprotic solvent. [ABSTRACT FROM AUTHOR]

Abstract Menispermaceae species, as early‐diverging eudicots, can synthesize valuable benzylisoquinoline alkaloids (BIAs) like bisbenzylisoquinoline alkaloids (bisBIAs) and sinomenines with a wide range of structural diversity. However, the evolutionary mechanisms responsible for their chemo‐diversity are not well understood. Here, a chromosome‐level genome assembly of Menispermum dauricum is presented and demonstrated the occurrence of two whole genome duplication (WGD) events that are shared by Ranunculales and specific to Menispermum, providing a model for understanding chromosomal evolution in early‐diverging eudicots. The biosynthetic pathway for diverse BIAs in M. dauricum is reconstructed by analyzing the transcriptome and metabolome. Additionally, five catalytic enzymes – one norcoclaurine synthase (NCS) and four cytochrome P450 monooxygenases (CYP450s) – from M. dauricum are responsible for the formation of the skeleton, hydroxylated modification, and C‐O/C‐C phenol coupling of BIAs. Notably, a novel leaf‐specific MdCYP80G10 enzyme that catalyzes C2′‐C4a phenol coupling of (S)‐reticuline into sinoacutine, the enantiomer of morphinan compounds, with predictable stereospecificity is discovered. Moreover, it is found that Menispermum‐specific CYP80 gene expansion, as well as tissue‐specific expression, has driven BIA diversity in Menispermaceae as compared to other Ranunculales species. This study sheds light on WGD occurrences in early‐diverging eudicots and the evolution of diverse BIA biosynthesis.

The article explores recent scientific research across various disciplines, including paleoceanography, planetary geophysics, and materials science. Topics discussed include the impact of climate change on nutrient transport in the North Atlantic, the volcanic activity on Jupiter's moon Io, and the observation of quantum anomalous Hall effect in two-dimensional materials.

The article focuses on the evolution of research on G protein–coupled receptors (GPCRs), the largest and most versatile class of cellular receptors, tracing the development of radioligand-binding techniques in the early 1970s that enabled the identification and study of receptors, particularly the β-2 adrenergic receptor (β2AR).

Finally, hydroboration of the enol carbamates derived from citronellal demonstrated a matched/mismatched effect wherein the I S i -methyl isomer was formed with a substantially higher dr than the I R i -methyl isomer. Keywords: hydroboration; Matteson homologation; Julia olefination; boronic esters; rhodium catalysis EN hydroboration Matteson homologation Julia olefination boronic esters rhodium catalysis 2181 2186 6 10/31/23 20231127 NES 231127 Graph The Matteson homologation remains a valuable synthetic transformation and a subject of continuing development 60 years after its initial disclosure. [28] We reasoned that asymmetric hydroboration of enol carbamates might produce -boryl carbamates with equal access to either enantiomer and a requirement for only catalytic quantities of the chiral controller (Scheme 1 F). [Extracted from the article]

The Diels Alder (D-A) reaction represents a crucial component of fundamental organic chemistry education and serves as a quintessential example of structural chemistry analyzed via basic principles of chemical sciences. This study explores the Diels-Alder reaction involving 1-methoxy-1,3-butadiene and acrolein, utilizing tools such as the Hückel molecular orbital (HMO) method, frontier molecular orbital (FMO) theory, and quantum chemical calculations. This approach provides detailed quantitative data and intuitive visual illustrations to elucidate the stereospecificity, regioselectivity, and stereoselectivity inherent to this reaction. The findings from this study serve as valuable resources for students, not only enhancing their understanding of D-A reaction properties and principles, but also developing their interest in computational chemistry and augmenting their problem-solving acumen. [ABSTRACT FROM AUTHOR]

Two approaches to the synthesis of para-menthene epoxide ((1S,5S,6R)-4) are developed. The first approach includes a reaction between chlorohydrin 7 and NaH in THF. The second involves the formation of epoxide in the reaction of corresponding diacetate 6 with sodium tert-butoxide. One possible mechanism of this reaction is proposed to explain unexpected outcomes in the regio- and stereospecificity of epoxide (1S,5S,6R)-4 formation. The epoxide ring in (1S,5S,6R)-4 is then opened by various S- and O-nucleophiles. This series of reactions allows for the stereoselective synthesis of diverse derivatives of the monoterpenoid Prottremine 1, a compound known for its antiparkinsonian activity, including promising antiparkinsonian properties. [ABSTRACT FROM AUTHOR]

Central‐atom effects on bimolecular nucleophilic substitution (SN2) reactions are well‐known in chemistry, however, the atomic‐level SN2 dynamics at phosphorous (P) centers has never been studied. We investigate the dynamics of the F−+PH2Cl reaction with the quasi‐classical trajectory method on a novel full‐dimensional analytical potential energy surface fitted on high‐level ab initio data. Our computations reveal intermediate dynamics compared to the F−+CH3Cl and the F−+NH2Cl SN2 reactions: phosphorus as central atom leads to a more indirect SN2 reaction with extensive complex‐formation with respect to the carbon‐centered one, however, the title reaction is more direct than its N‐centered pair. Stereospecificity, characteristic at C‐center, does not appear here either, due to the submerged front‐side‐attack retention path and the repeated entrance‐channel inversional motion, whereas the multi‐inversion mechanism discovered at nitrogen center is also undermined by the deep Walden‐well. At low collision energies, 6 % of the PH2F products form with retained configuration, mostly through complex‐mediated mechanisms, while this ratio reaches 24 % at the highest energy due to the increasing dominance of the direct front‐side mechanism and the smaller chance for hitting the deep Walden‐inversion minimum. Our results suggest pronounced central‐atom effects in SN2 reactions, which can fundamentally change their (stereo)dynamics. [ABSTRACT FROM AUTHOR]

We have disclosed a Rauhut–Currier reaction of γ-alkyl-substituted allenoate, catalyzed by L -valine-derived amide phosphine, to form trisubstitued allenoate, which was trapped by maleimide or DMAD via the Diels–Alder reaction. Exo-bicyclic succinimide derivatives including three continuous stereocenters with an exo-carbon–carbon double bound were constructed in up to quantitative yields with high stereospecificity. [ABSTRACT FROM AUTHOR]

The combination of the catalytic power of amorphous metal‐organic frameworks (aMOFs) and biocatalysis has greatly boosted the development of novel synthetic strategies due to its functional diversity and stereospecificity. 2‐Cyanoacrylamides are important building blocks for many biologically active molecules. Herein, we described a chemical‐biological relay catalytic method to access (E)‐2‐cyanoacrylamides based on the catalysis of amorphous porphyrin‐MOFs SPUZ‐1 and whole cells of Rhodococcus rhodochrous (nitrile hydratase). The approach was proved to be simple and efficient, and the highest conversion was up to 99% [ABSTRACT FROM AUTHOR]

In this paper, the anti-cancer activity and molecular mechanisms of the isomers of AD-1 and AD-2 (20(R)-AD-1, 20(R)-AD-2, 20(S)-AD-1 and 20(S)-AD-2) were investigated. The results indicated that all of the four compounds obviously suppressed the viability of various cancer cells, and the anti-cancer activity of 20(R)-AD-1 and 20(R)-AD-2 was significantly better than 20(S)-AD-1 and 20(S)-AD-2, especially for gastric cancer cells (BGC-803). Then, the differences in the anti-cancer mechanisms of the isomers were investigated. The data showed that 20(R)-AD-1 and 20(R)-AD-2 induced apoptosis and decreased MMP, up-regulated the expression of cytochrome C in cytosol, transferred Bax to the mitochondria, suppressed oxidative phosphorylation and glycolysis and stimulated reactive oxygen species (ROS) production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. However, 20(S)-AD-1 and 20(S)-AD-2 barely exhibited the same results. The results indicated that 20(R)-AD-1 and 20(R)-AD-2 suppressed cellular energy metabolism and caused apoptosis through the mitochondrial pathway, which ROS generation was probably involved in. Above all, the data support the development of 20(R)-AD-1 and 20(R)-AD-2 as potential agents for human gastric carcinoma therapy. [ABSTRACT FROM AUTHOR]

[34] The reaction with enantioenriched -methylbenzylboronic acid pinacol ester resulted in a 56:44 diastereomeric mixture of alcohol products B 48 b , the same diastereomeric mixture as was observed using racemic alkylboronic ester. [3][5][6] This short review details our laboratory's examination of reactions using benzylboronic acid pinacol ester and secondary and tertiary benzylboronic esters as nucleophiles. Keywords: boron; benzylation; Lewis base; copper; boronate EN boron benzylation Lewis base copper boronate 2639 2647 9 08/17/23 20230901 NES 230901 Graph 1 Introduction Organoboranes have found great utility in organic synthesis. Specifically, substrates containing esters and amides to the ketone were found to be compatible under these reaction conditions with no reaction being observed at the ester or amide carbonyl carbon ( B 25 b and B 26 b ). [Extracted from the article]

We report a copper‐catalyzed, regioselective, and stereospecific alkylation of unbiased internal allylic carbonates with functionalized alkyl and aryl Grignard reagents. The reactions exhibit high stereospecificity and regioselectivity for either SN2 or SN2′ products under two sets of copper‐catalyzed conditions, which enables the preparation of a broad range of products with E‐alkene selectivity. Density functional theory calculations reveal the origins of the regioselectivity based on the different behaviors of homo‐ and heterocuprates. [ABSTRACT FROM AUTHOR]

Silicon‐based compounds with stereochemical information and convertible functional units are valuable building blocks in synthetic chemistry. Si‐stereogenic aminochlorosilanes are built up by Si−N bond formation between an achiral dichlorosilane and a chiral enantiomerically pure primary amine. Both diastereomers could be isolated as stereochemically pure single‐crystals by fractional crystallization and were analyzed by X‐ray crystallography. Defined intermolecular interaction patterns were identified illustrating the role of N−H⋅⋅⋅π, C−H⋅⋅⋅π, and N−H⋅⋅⋅Cl contacts in the molecular crystalline packing arrangements. Stepwise functionalization of the silicon−chlorine and silicon−amine functions was carried out, demonstrating their potential for use as a chiral synthesis precursors. Via optically pure aminomethoxysilanes, enantiomerically enriched methoxysilanols, chloromethoxysilanes, and methoxysilanethiols were synthesized. The stereospecificity of the transformations was monitored. The (R)‐BINOL‐PSSLi method for determining the enantiomeric purity was found to be the tool of choice for acid‐sensitive silanols and silanethiols. [ABSTRACT FROM AUTHOR]

In this publication, we reported an eco-friendly procedure for the efficient synthesis of 2-imino-5-(1-alkyl-2-oxoindolin-3-ylidene) thiazolidin-4-one derivatives with a stereospecific coupling reaction between 2-imino-thiazolidin-4-one (pseudothiohydantoin) and cyano-substituted oxindole derivatives. Thus, a variety of new thiazolidin-oxindole derivatives with potential medicinal applications have been synthesized with an effective and economical method, focusing on sustainable chemistry. The final products have been obtained in excellent yields together with high purity after washing with water and ethanol. This publication is the first easy protocol to be reported for the rapid condensation of pseudothiohydantoin with substituted isatins. In addition, the stereospecificity, which led to the formation of the Z- isomer of the products is validated using computational calculations. [ABSTRACT FROM AUTHOR]

We describe a highly diastereo‐ and enantioselective two‐step formal anti‐Markovnikov addition of H2O to diastereomeric mixtures of trisubstituted olefins. Our approach overcomes the limits of classical stereospecific addition reactions to olefins for the generation of adjacent stereocenters. In these stereospecific reactions, separation of olefin diastereomers is essential. Our method circumvents the need for such difficult separations by simultaneously employing both diastereomeric olefins in the organocatalytic, highly enantioselective, syn‐specific Shi‐epoxidation to yield diastereomeric oxiranes. The stereochemical model proposes the smallest substituent on the olefin to be stereodefining resulting in an identical enantiotopic approach for both olefin isomers on the less substituted carbon. By employing a stereoconverging epoxide hydrosilylation the identically configured center is retained, while the differing one is converted to a planar radical center that is reduced by a syn‐selective intramolecular hydrogen atom transfer (HAT) from a Ti−H bond. The observed converging behavior can be attributed to a HAT‐preceding directional isomerization step, that interconverts the obtained rotameric radicals which ultimately leads to high to excellent enantiomeric ratios of the final secondary alcohols. [ABSTRACT FROM AUTHOR]

Sulfoximines and sulfonimidamides are of interest as design options for medicinal chemists. This article describes the development of methods for the synthesis of sulfoximines by metal-free NH-transfer to sulfoxides, and NH/O transfer to sulfides, using convenient sources of ammonia and hypervalent iodine reagents. Similarly, sulfonimidamides are prepared from sulfenamides. Methods for the preparation of enantioenriched sulfonimidoyl fluorides are also described, as are their stereospecific reactions with amines and Grignard reagents. This work was presented at the 29th International Symposium on the Organic Chemistry of Sulfur (Guelph, July 2022). [ABSTRACT FROM AUTHOR]

Sphingobium sp. strain SYK-6 is an efficient aromatic catabolic bacterium that can consume all four stereoisomers of 1,2-diguaiacylpropane-1,3-diol (DGPD), which is a ring-opened β-1-type dimer. Recently, LdpA-mediated catabolism of erythro-DGPD was reported in SYK-6, but the catabolic pathway for threo-DGPD was as yet unknown. Here, we elucidated the catabolism of threo-DGPD, which proceeds through conversion to erythro-DGPD. When threo-DGPD was incubated with SYK-6, the Ca hydroxy groups of threo-DGPD (DGPD I and II) were initially oxidized to produce the Ca carbonyl form (DGPDketo I and II). This initial oxidation step is catalyzed by Ca-dehydrogenases, which belong to the short-chain dehydrogenase/reductase (SDR) family and are involved in the catabolism of β-O-4-type dimers. Analysis of seven candidate genes revealed that NAD1-dependent LigD and LigL are mainly involved in the conversion of DGPD I and II, respectively. Next, we found that DGPD-keto I and II were reduced to erythro-DGPD (DGPD III and IV) in the presence of NADPH. Genes involved in this reduction were sought from Ca-dehydrogenase and ldpA-neighboring SDR genes. The gene products of SLG_12690 (ldpC) and SLG_12640 (ldpB) catalyzed the NADPH-dependent conversion of DGPD-keto I to DGPD III and DGPDketo II to DGPD IV, respectively. Mutational analysis further indicated that ldpC and ldpB are predominantly involved in the reduction of DGPD-keto. Together, these results demonstrate that SYK-6 harbors a comprehensive catabolic enzyme system to utilize all four β-1-type stereoisomers through successive oxidation and reduction reactions of the Cα hydroxy group of threo-DGPD with a net stereoinversion using multiple dehydrogenases. IMPORTANCE In many catalytic depolymerization processes of lignin polymers, aryl-ether bonds are selectively cleaved, leaving carbon-carbon bonds between aromatic units intact, including dimers and oligomers with b-1 linkages. Therefore, elucidating the catabolic system of b-1-type lignin-derived compounds will aid in the establishment of biological funneling of heterologous lignin-derived aromatic compounds to value-added products. Here, we found that threo-DGPD was converted by successive stereoselective oxidation and reduction at the Ca position by multiple alcohol dehydrogenases to erythro-DGPD, which is further catabolized. This system is very similar to that developed to obtain enantiopure alcohols from racemic alcohols by artificially combining two enantiocomplementary alcohol dehydrogenases. The results presented here demonstrate that SYK-6 has evolved to catabolize all four stereoisomers of DGPD by incorporating this stereoinversion system into its native β-1-type dimer catabolic system. [ABSTRACT FROM AUTHOR]

S-Glycosides are considerably more stable toward chemical degradation and enzymatic hydrolysis than O-glycosides, and thioglyco-peptides/proteins also demonstrate critical bioactivities in the living system. However, the general and stereoselective synthetic strategies are still challenging. Herein, a versatile S-glycosylation approach was developed by palladium-catalyzed allylic substitution to form a- and ß-thioglycosides respectively under mild conditions. A wide range of substrates were tolerated to afford thioglycosides in a stereospecific manner with 70%-86% yields. This protocol also created the quick access to various S-linked disaccharides and glycopeptides. [ABSTRACT FROM AUTHOR]

Herein we reported a transition metal‐free deborylative cyclization strategy, based on which two routes have been developed, generating racemic and enantioenriched cyclopropylboronates. The cyclization of geminal‐bis(boronates) bearing a leaving group was highly diastereoselective, tolerating a few functional groups and applicable to heterocycles. When optically active epoxides were used as the starting materials, enantioenriched cyclopropylboronates could be efficiently prepared with >99 % stereospecificity. Mechanistic studies showed that the leaving group at the γ‐position played a crucial role and significantly promoted the activation of the gem‐diboron moiety. [ABSTRACT FROM AUTHOR]