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This review highlights the use of DACH as a versatile ligand in catalytic asymmetric transformations providing mechanistic rationales and relevant comments presented in chronological order for each of the 21 reaction types with references up to December 25, 2023. Intended to be as practically comprehensive as possible, this review assembles useful examples of using DACH as a ligand in organocatalytic or as metal complexes in asymmetric transformations. The resulting enantiomerically enriched, if not pure, chiral non-racemic small molecules are of great utility as value added intermediates in the total synthesis of natural products, in the design and synthesis of medicinally important compounds, and in other areas in organic and bioorganic chemistry where chirality plays a role. The graphic image depicts Spartacus with his arms folded in the same sense of chirality as (R , R)-DACH. 1 Introduction 2 DACH: A Brief Historical Narrative 3 Catalytic Asymmetric Hydrogenation of Alkenes 4 Catalytic Asymmetric Dihydroxylation of Alkenes 5 Catalytic Asymmetric Sulfoxidation and Sulfimidation 6 Catalytic Asymmetric 1,4-Conjugate Addition 6.1 Using Jacobsen's DACH Metal–salen Complexes as Catalysts 6.2 Using Takemoto's Bifunctional H-Bonding DACH Thiourea Organocatalyst 6.3 Using DACH Ni(II) Complexes as Catalysts 6.4 Using DACH H-Bonding Catalysis 7 Catalytic Asymmetric Epoxidation of Alkenes 8 Catalytic Asymmetric Claisen Rearrangement 9 Catalytic Asymmetric 1,2-Nucleophilic Addition to Carbonyl Compounds 9.1 Catalytic Asymmetric Addition of Dialkylzinc to Aldehydes and Ketones 9.2 Catalytic Asymmetric Alkynylation of Aldehydes and Ketones 9.3 Catalytic Asymmetric Addition of Cyanide to Aldehydes and Ketones 10 Catalytic Asymmetric Allylic Alkylation 11 Catalytic Asymmetric Cyclopropanation of Alkenes 12 Catalytic Asymmetric Cycloaddition Reactions 13 Catalytic Asymmetric Aziridination of Alkenes 14 Catalytic Asymmetric Hydrogenation of Prochiral Ketones and Imines 15 Catalytic Asymmetric Aldol Reactions 16 Catalytic Asymmetric Opening of Small Ring Systems 16.1 Desymmetrization of meso -Epoxides and meso -Aziridines 16.2 Kinetic Resolution of Racemic Epoxides 16.3 Enantioselective Addition of CO2 to Epoxides 16.4 Enantioselective Ring Opening of Oxetanes 17 Catalytic Asymmetric Strecker Reactions 18 Catalytic Asymmetric Mannich Reactions 19 Catalytic Asymmetric Henry and Aza-Henry Reactions 20 Catalytic Asymmetric Morita–Baylis–Hillman and Rauhut–Currier Reactions 21 Catalytic Asymmetric Petasis Reactions 22 Organocatalytic Asymmetric Cascade Reactions 23 Miscellaneous Catalytic Reactions 24 Conclusion and Outlook 25 DACH Catalysts and Ligands List [ABSTRACT FROM AUTHOR]

In this study, p-morpholinomethylcalix[4]arene (p-MC4) was synthesized using Mannich reaction and utilized for the fabrication of polyacrylonitrile nanofibers impregnated with p-morpholinomethylcalix[4]arene (PAN/p-MC4) using electrospinning. The nanofibers were prepared by blending 12% solution of PAN with 20% solution of p-MC4. The PAN/p-MC4 NFs were thoroughly evaluated for their removal efficiency of Cu2+ from the aqueous media. The selectivity of PAN/-p-MC4 nanofibers was also examined by adsorbing a set of metal ions with same charge and similar ionic radius. The results of distribution ratio showed that PAN/p-MC4 nanofibers have superior selectivity for Cu2+ as compared to other heavy metal ions. The relative selectivity coefficients of PAN/p-MC4 nanofibers were found to be 25.2, 14.1, 8.9, and 4.03 for Cu2+/Ni2+, Cu2+/Co2+, Cu2+/Cd2+ and Cu2+/Pb2+, respectively. This indicates that PAN/p-MC4 nanofibers have a higher selectivity for Cu2+ ions. Numerous parameters such as pH, time, adsorbent dosage and analyte concentration were optimized to evaluate the maximum adsorption capacity of nanofibers for Cu2+. Adsorption isotherm models showed that the adsorption is promising and follows Langmuir adsorption isotherm. Whereas, PAN/p-MC4 nanofibers followed pseudo- second order kinetics during adsorption experiments. The PAN/p-MC4 nanofibers showed excellent adsorption capacity (qo) of 65.35 mg/g for Cu2+ at pH 5 in 60 min under shaking speed of 120 rpm. Moreover, PAN/p-MC4 nanofibers had been used to remove Cu2+ from real surface water samples. According to the results, PAN/p-MC4 nanofibers are more effective adsorbent for removing Cu2+ from contaminated water. [ABSTRACT FROM AUTHOR]

We report the detailed mechanistic insights of L-proline catalyzed, solvent-controlled, regioselective Mannich reaction. Different solvation models were employed to understand the formation of critical intermediates. The seminal difference in the nature of H-acceptor solvents and H-donor solvents leads to variation in the attachment site on the reactant molecule. Our calculations suggest that the H-acceptor solvent exhibits selective non-covalent interaction with α-hydrogen atoms of the iminium group, facilitating the reactivity at the more hindered site, which results in the formation of a branched isomer. On the other hand, the H-donor solvent preferentially binds to the carboxylate group, thus enabling the reactivity to proceed from the less hindered carbon chain, leading to a linear isomer. The above distinct interactions force a regioselective generation of enamines. Thus, the iminium ion's site-specific solvent interaction has been observed to cause a switch in the regioselectivity. These enamines subsequently react with cyclic ketone to produce Mannich base with excellent enantioselectivity (>99%ee). [ABSTRACT FROM AUTHOR]

Acid recovery from acidic waste is a pressing issue in current times. Chemical methods for recovery are not economically feasible and require significant energy input to save the environment. This study reported a semi‐interpenetrating polymer network (semi‐IPN) anion exchange membranes (AEMs) for acid recovery by diffusion dialysis with excellent dimensional stability, high oxidation stability, good acid dialysis coefficient (UH+) and high separation factor (S). Semi‐IPN AEMs are prepared by ring‐open cross‐linked quaternized polybenzoxazine (AQBZ) with poly(vinyl alcohol‐co‐ethylene), where AQBZ is obtained by Mannich reaction and Menshutkin reaction. All four proportions of semi‐IPNs exhibit clear micro‐phase separation, which is conducive to ion transport. The water uptake (WU) of the four semi‐IPNs ranges from 14.2 % to 19.2 %, while the swelling ratio (SR) remains between 8.7 % and 11.3 %. These results indicate that the cross‐linked structure in the designed semi‐IPNs effectively control swelling and ensure dimensional stability. The thermal degradation temperature (Td5) of semi‐IPN4:6 to semi‐IPN7:3 varies from 309 °C to 289 °C, with an oxidation stability weight loss rate (WOX) ranging from 91.5 % to 93.5 %, demonstrating excellent thermal stability and oxidation stability. The semi‐IPNs also show good UH+ values ranging from 11.9–16.3*10−3 m/h and high S values between 38.6 and 45.9, indicating the promising potential of the semi‐IPNs. [ABSTRACT FROM AUTHOR]

Meglumine, an amino sugar alcohol compound, has recently emerged as a promising catalyst in various organic transformations due to its unique properties. This review provides a comprehensive overview of the applications of meglumine catalyst in organic synthesis, highlighting their efficiency, versatility, and mechanistic insights. Key examples of reactions catalyzed by meglumine, including aldol condensation, Michael addition, Mannich reaction, and other one-pot multicomponent condensation reaction are discussed along with mechanistic pathways and synthetic strategies. Additionally, recent advancements and future perspectives in the field are explored. [ABSTRACT FROM AUTHOR]

An efficient cascade cyclization strategy was developed to synthesize aminobenzofuran spiroindanone and spirobarbituric acid derivatives utilizing 2-bromo-1,3-indandione, 5-bromo-1,3-dimethylbarbituric acid, and ortho-hydroxy α-aminosulfones as substrates. Under the optimized reaction conditions, the corresponding products were obtained with high efficiency, exceeding 95% and 85% yields for the respective derivatives. This protocol demonstrates exceptional substrate versatility and robust scalability up to the Gram scale, establishing a stable platform for the synthesis of 3-aminobenzofuran derivative. The successful synthesis paves the way for further biological evaluations with potential implications in scientific research. [ABSTRACT FROM AUTHOR]

Covalent polymerization of organic molecules into crystalline one‐dimensional (1D) polymers is effective for achieving desired thermal, optical, and electrical properties, yet it remains a persistent synthetic challenge for their inherent tendency to adopt amorphous or semicrystalline phases. Here we report a strategy to synthesize crystalline 1D covalent organic frameworks (COFs) composing quasi‐conjugated chains with benzoxazine linkages via the one‐pot Mannich reaction. Through [4+2] and [2+2] type Mannich condensation reactions, we fabricated stoichiometric and sub‐stoichiometric 1D covalent polymeric chains, respectively, using doubly and singly linked benzoxazine rings. The validity of their crystal structures has been directly visualized through state‐of‐the‐art cryogenic low‐dose electron microscopy techniques. Post‐synthetic functionalizations of them with a chiral MacMillan catalyst produce crystalline organic photocatalysts that demonstrated excellent catalytic and recyclable performance in light‐driven asymmetric alkylation of aldehydes, affording up to 94 % enantiomeric excess [ABSTRACT FROM AUTHOR]

Asymmetric decarboxylative Mannich addition of β‐keto acids or malonic acid half‐esters to β,γ‐alkynyl‐α‐ketimino esters catalyzed by cinchona alkaloid‐derived squaramide has been developed. The reaction proceeded by forming a nucleophilic enolate after decarboxylation, followed by its addition to β,γ‐alkynyl‐α‐ketimino esters facilitated by the bifunctional catalyst. A broad range of substrates with various substituents are tolerated in this reaction, yielding a series of α,α‐disubstituted amino acid derivatives bearing alkynyl functional groups in high yields with good to excellent enantioselectivities. The practicality of this method was demonstrated by a gram‐scale reaction and subsequent elaboration of the Mannich adducts. [ABSTRACT FROM AUTHOR]

Organic fluorides are widely used in pharmaceuticals, agrochemicals, material sciences, and other fields due to the special physical and chemical properties of fluorine atoms. The synthesis of alkyl fluorinated compounds bearing multiple contiguous stereogenic centers is the most challenging research area in synthetic chemistry and has received extensive attention from chemists. This review summarized the important research progress in the field over the past decade, including asymmetric electrophilic fluorination and the asymmetric elaboration of fluorinated substrates (such as allylic alkylation reactions, hydrofunctionalization reactions, Mannich addition reactions, Michael addition reactions, aldol addition reactions, and miscellaneous reactions), with an emphasis on synthetic methodologies, substrate scopes, and reaction mechanisms. [ABSTRACT FROM AUTHOR]

Hollongdione is the first recorded example of the occurrence of a dammarane hexanor-triterpene in nature possessing antiviral and cytotoxic activity. Its simple one-stage transformation into compounds with terminal alkyne and vinyl chloride fragments via the interaction with phosphorus halides is reported. The copper(I)-catalyzed Mannich reaction of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20(21)-in 3 led to a series of aminomethylated products, while 17-carboxylic acid was obtained by ozone oxidation of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20-chloro-20(21)-en 4; the following direct amidation of the latter has been developed. The structures of all new molecules were established by spectroscopic studies that included 2D NMR correlation methods; the molecular structures of compounds 2–5 were determined by X-ray analysis. [ABSTRACT FROM AUTHOR]

A series of novel trans-3-substituted aminomethyl-5-(4-(4-chlorophenyl)cyclohexyl)-1,3,4-oxadiazole-2(3H)-thiones was synthesized successfully from achiral trans-4-(4-chlorophenyl)cyclohexane-1-carboxylic acid. To investigate their potential binding interactions with proteins at the active site, molecular docking studies were conducted using CDOCKER module (Biovia Discovery Studio 2022) against Penicillin Binding Protein 2 of Escherichia coli (PDB: 6G9F) and Pseudomonas aeruginosa (PDB: 7KIS). The results of the docking studies indicate that the compounds exhibit limited binding efficacy. Molecular Dynamics simulations were carried out for Ceftazidime to predict the ligand binding status in the physiological environment. The antibacterial in-vitro inhibitory potential was evaluated against a panel of microorganisms consisting of two Gram-positive bacterial strains, Bacillus subtilis (ATCC6633) and Staphylococcus aureus (ATCC6538), as well as three Gram-negative bacterial strains, Pseudomonas aeruginosa (ATCC9027), Escherichia coli (ATCC8739), and Salmonella typhi (ATCC9207). The N-Mannich bases displayed promising antibacterial activity against both the Gram-positive microorganisms and demonstrated effective inhibition of Escherichia coli. However, their activity against Pseudomonas aeruginosa was moderate. The binding affinity to Penicillin Binding Proteins was evaluated by observing morphological changes in Escherichia coli rods under an optical microscope. The results revealed a notable decrease in cell count without observable morphological changes, indicating that the N-Mannich bases do not bind strongly to Penicillin Binding Proteins and likely operate through an alternative mechanism. The antifungal activity against Saccharomyces cerevisiae (ATCC9763) and Aspergillus niger (ATCC16404) was not observed. [ABSTRACT FROM AUTHOR]

The histone deacetylases (HDACs) are being explored as a promising therapeutic target for the treatment of various diseases. Here, the synthesis of a series of pyrimidine‐based 1,3,4‐oxadiazoles, in which the oxadiazole scaffold is attached to the pyrimidine ring via a methyleneoxy spacer, is described and their HDAC inhibitory activity studied. The target compounds were synthesized by sequence of reactions involving O‐alkylation of 2‐(methylthio)pyrimidin‐4(3H)‐ones with ethyl 2‐bromoethanoate followed by oxidation of the 2‐methylthio group, displacement of the obtained 2‐methylsulfonyl group with amines, hydrazinolysis of the obtained ethyl (2‐amino‐substituted pyrimidin‐4‐yloxy)acetates to give the corresponding hydrazides and their cyclization under the treatment with ethyl O‐ethyl xanthate or carbonyldiimidazole to 1,3,4‐oxadiazole‐2(3H)‐thiones and 1,3,4‐oxadiazol‐2(3H)‐one, correspondingly. In addition, two 1,3,4‐oxadiazole‐2(3H)‐thiones were converted into (N3)‐morpholinomethyl derivatives by the Mannich reaction with formaldehyde and morpholine. The yields of intermediates and target compounds ranged from moderate to excellent. The synthesized compounds were characterized by 1H and 13C NMR spectra and HRMS data, their purity was controlled by TLC. The synthesized pyrimidine‐based 1,3,4‐oxadiazoles (18 compounds) were tested as inhibitors of the HDAC4 and HDAC8 isoforms and their inhibitory activity was compared with that of Vorinostat. Most of the oxadiazolethiones containing methyl group at the position 6 of the pyrimidine moiety were found to be more selective towards HDAC8, while oxadiazolethiones with propyl group in the pyrimidine ring were active against HDAC4. Among the tested compounds, 5‐((2‐(dibutylamino)‐6‐propylpyrimidin‐4‐yloxy)methyl)‐1,3,4‐oxadiazole‐2(3H)‐thione (48) was found to have the strongest inhibitory activity for HDAC4 isoform (IC50 = 4.2 μM vs. IC50 = 59 μM for Vorinostat) while 5‐((2‐(cyclopentylamino)‐6‐propylpyrimidin‐4‐yloxy)methyl)‐1,3,4‐oxadiazole‐2(3H)‐thione (50) was the most potent HDAC8 inhibitor (IC50 = 6.8 μM). [ABSTRACT FROM AUTHOR]

Conformationally flexible tertiary amine – thiourea−urea catalysts 1 and 2 for the Mannich reaction between imines and malonate esters are efficiently inhibited by quaternary ammonium halides. NMR titrations, isothermal titration calorimetry (ITC) and NOE experiments showed that the catalysts bind chloride and bromide ions with relatively high affinities (K=103–105 M−1 in acetonitrile). The halide ions not only block the active site of the catalysts, but they also induce refolding into catalytically inactive conformations upon complexation in an allosteric‐like event. At substoichiometric inhibitor:catalyst ratios, the catalysts displayed hypersensitivity to the inhibitors, with overall rates that were lower than those expected from simple 1st order kinetics and 1 : 1 inhibitor:catalyst stoichiometry. To rationalize the observed hypersensitivity, different kinetic scenarios were examined. For catalyst 2 and the Takemoto catalyst (6), the data is consistent with 2nd order dependency on catalyst concentration, suggesting that a mechanism involving only a single catalyst in the catalytic cycle is not operative. For catalyst 1, an alternative scenario involving 1st order in catalyst and catalyst poisoning at low concentrations of 1 could also rationalize the hypersensitivity. Interestingly, inhibition of catalysts 1 and 2 by halide salts led to significant loss of enantioselectivity, in contrast to the Takemoto catalyst 6 which was inhibited but with essentially no change in enantioselectivity. [ABSTRACT FROM AUTHOR]

The preparation of Fe(II) complexes combining monodentate NCX− (X = S or Se) and the tetradentate Schiff base chiral ligands RR-L1 and SS-L1 = (RR- or SS-L1 = 1R,2R or 1S,2S)-N1,N2-bis(pyridin-2-ylmethylen)cyclohexane-1,2-diamine in acetone results in an unexpected reaction. Thus, four enantiomerically pure compounds of formulas [Fe(RR-S-L2)(NCX)2] and [Fe(SS-R-L2)(NCX)2] (X = S or Se) are formed by the new asymmetrical ligand L2. In L2, one acetone solvent molecule is incorporated into the ligand forming a bond with the C atom of one of the two CN imine groups of L1, which is transformed into an amine (Mannich reaction). This reaction is diastereoselective as the incorporation of acetone leads to an asymmetric C adjacent to the NH group with opposite chirality S- or R- to that of the cyclohexane carbons (RR- or SS-, respectively). Therefore, L2 contains three C chiral centers. Structural and magnetic characterization of these compounds demonstrates that they show in the bulk a gradual spin-crossover behavior and LIESST effect. Interestingly, the presence of an intramolecular hydrogen bond between the integrated acetone molecule and the NH group can trigger a secondary stimuli-responsive behavior in the system. Therefore, by changing the solvent polarity, the color of the complex in solution can be easily tuned. [ABSTRACT FROM AUTHOR]

fter reviewing a number of researches that demonstrate the effectiveness of a number of compounds containing the acetylenic amine group as antimicrobials and antiproliferative activity, our goal is to prepare new acetylenic amine derivatives from the compound 2-(2-((2,6- dichlorophenyl)amino)phenyl)acetic acid using the Mannich reaction by the react salt of a carboxylic acid with propargyl bromide to produce the compound (prop-2-yn-1-yl 2-(2-((2,6- dichlorophenyl)amino)phenyl)acetate) (1), which was refluxed with a number of secondary amines and formaldehyde in presence of the copper chloride as a catalyst to obtain 7 compounds (4-(dialkylamino)but2-yn-1-yl 2-(2-((2,6-dichlorophenyl)amino)phenyl)acetate)(2-8). The physical and spectral properties of the prepared compounds were measured, and the bioassay conducted for some substances by investigating their antibiotic activity. The two compounds (1,2) were also selected to test their anticancer activity against one of its types, a breast cancer cell line (MCF-7), using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using multiple concentrations compared to the normal cell line (WRL-68). The previous results showed the effect of the two compounds on the cancer cell line more than its effect on the normal cell line, the results showed significant differences (p≤0.0001) by calculating the (IC50) when treating compounds (1,2) for MCF-7 cancer cells at (250,300) µg/ml and for normal cells at (983,1292) µg/ml respectively. It is believed that the reason for its effectiveness is because contains acetylenic amine in compound (1) in addition to morpholine ring in compound (2), which research has proven to be effective in multiple medicines. Some pharmacokinetic activities of the prepared compounds have been predicted to support the discovery of new drugs using the Swiss ADME website. [ABSTRACT FROM AUTHOR]

This study includes the preparation and characterization of new compound (4-bromo-5-(N-((4- chlorophenyl) (1,1-dioxide-3-oxobenzo isothiazol-2(3H)-yl)methyl)sulfamoyl)-2-((furan2-ylmethyl)amino)benzoic acid) from the reaction of furosemide, Saccharin and p-bromo benzaldehyde in a molar ratio 1:1:1 in ethanol. All the complexes are prepared from the reaction of Mannich bases with metal nitrate salts of transition metals such as Co, Ni, Cu and Zn in equimolar ratio (1:1) in ethanol solvent. The prepared compounds were characterized by elemental analysis (C.H.N.S), H-NMR, FT-IR, molar conductivity and magnetic sensitivity were determined. The results showed that furosemide derivatives bidentate are coordinated by nitrogen and oxygen atoms with metal, giving tetrahedral geometry. The antibacterial activity was studied for ligands and their complexes using the agar diffusion method. All the prepared compounds were studied and applied to two types of bacteria at different concentrations. It was showed, that the obtained complexes demonstrate a higher inhibitory effect on Staphylococcus aureas bacteria than on Pseudomonas aeruginosa bacteria. [ABSTRACT FROM AUTHOR]

An efficient and practical organocatalyzed asymmetric Mannich/cyclization tandem reaction strategy of 2-benzothiazolimines and 2-isothiocyanato-1-indanones was developed, and novel spirocyclic compounds containing benzothiazolimine and indanone scaffolds were obtained. This chiral thiourea-catalyzed Mannich/cyclization tandem reaction offers chiral spirocyclic compounds with continuous tertiary and quaternary stereocenters in good to high yields (up to 90%) with excellent diastereoselectivities (up to >20:1 dr) and enantioselectivities (up to 98% ee) at −18 ◦C. Additionally, the scaled-up synthesis was also performed with retained yield and stereoselectivity, and a reaction mechanism was also proposed. [ABSTRACT FROM AUTHOR]

Polybenzoxazines are a class of luminescent polymers that exhibit light emission properties, making them suitable for various applications. This manuscript presents the synthesis, characterization, and thermal behavior of a novel luminescent polybenzoxazine, named P‐BZ‐CP. The synthesis of P‐BZ‐CP involved a three‐stage process, starting with the formation of Bis‐OHOMe through the reaction of cyclopentanone and vanillin, followed by a Mannich condensation reaction with p‐toluidine to obtain the monomer M‐BZ‐CP. Thermal ring‐opening polymerization of M‐BZ‐CP at 250°C resulted in the synthesis of P‐BZ‐CP. Comprehensive characterization techniques, including NMR, FTIR, XRD, SEM, TGA, and DSC, were employed to analyze the structure and properties of both M‐BZ‐CP and P‐BZ‐CP. The thermal behavior of M‐BZ‐CP curing was investigated using DSC, highlighting the temperature‐dependent polymerization process. This work also provides insights into the photophysical properties of Bis‐OHOMe, M‐BZ‐CP, and P‐BZ‐CP, highlighting the role of molecular structure and concentration in determining absorption, excitation, and emission characteristics. The core benzylidene cyclopentanone chromophore contributes to the common absorption and emission features, while the additional functional groups in M‐BZ‐CP lead to concentration‐dependent photoluminescence behavior due to aggregation or excimer formation. These findings demonstrate the importance of understanding the structure–property relationships in designing optoelectronic materials with tunable photophysical properties. The findings demonstrate the successful synthesis and characterization of luminescent polybenzoxazines, providing valuable insights into their potential applications in optoelectronics. [ABSTRACT FROM AUTHOR]

Over the past 20 years, there has been a notable rise in the incidence of invasive bacterial infections. This increase has been mostly linked to the growth of drug‐resistant bacteria. Tetrazoles have been considered as promising antibacterial agents and their effectiveness may be enhanced by hybridization with other antibacterial pharmacophores. In this work, a series of tetrazole hybrids (1‐6) containing oxazepane and pyrazole rings as well as Mannich bases (7,8) were synthesized via the Schiff and Mannich reactions, respectively. The compositions were proven spectroscopically using infrared spectra, proton (1H) and carbon‐13 (13C) nuclear magnetic resonance spectra and elemental analyses. Moreover, the pharmacokinetic properties viz Absorption, Distribution, Metabolism and Excretion (ADME) were predicted in silico using SwissADME server. Compounds 1,2 and 4–6 attaining the best drug‐likeness properties were screened for their antibacterial activities against Staphylococcus epidermidis and Streptococcus mutans at different concentrations in comparison with tetracycline and amikacin, respectively. Afterwards, a molecular docking study was performed to explore the potential binding patterns of the new antibacterial compounds. Collectively, the tetrazole hybrids 4 and 5 have been found to have higher inhibitory potencies compared to tetracycline, serving them as potential antibacterial candidates which can be further optimized in the future. [ABSTRACT FROM AUTHOR]

Double Mannich reaction with ketones is of continuing interest, particularly, in the synthesis of aza‐ and diaza‐heterocycles, alkaloids, and medicinally relevant compounds. The present review deals with the most important literature on the utility of double Mannich reaction in the synthesis and modification of heterocyclic systems. [ABSTRACT FROM AUTHOR]

Bacterial infections are the second-leading cause of death, globally. The prevalence of antibacterial resistance has kept the demand strong for the development of new and potent drug candidates. It has been demonstrated that Src protein tyrosine kinases (TKs) play an important role in the regulation of inflammatory responses to tissue injury, which can trigger the onset of several severe diseases. We carried out a search for novel Src protein TK inhibitors, commencing from reported highly potent anti-bacterial compounds obtained using the Mannich reaction, using a combination of e-pharmacophore modeling, virtual screening, ensemble docking, and core hopping. The top-scoring compounds from ligand-based virtual screening were modified using protein structure-based design approaches, and their binding to the Src homology-2 domain of p56lck TK was predicted using ensemble molecular docking. We have prepared a database of 202 small molecules and have identified six novel top hits that can be subjected to further investigation. We have also performed in silico ADMET property prediction for the hit compounds. This combined computer-aided drug design approach can serve as a starting point for identifying novel TK inhibitors that could be further subjected to in vitro studies and validation of antimicrobial activity. [ABSTRACT FROM AUTHOR]

New approaches based on multicomponent condensation reactions were proposed to the synthesis of new heterocyclic derivatives of malononitrile dimer of the series of 7-oxa-1,3,6-triazabenzo[no]tetraphene, 1,2,3,4-tetrahydropyrazolo[1,5-a][1,3,5]triazine, 1,3,5,5-tetracyanocyclohex-3-ene, 3,9-diazaspiro[5.5]undeca-1,4-diene and 1Н,5Н-spiro[3,7-diazabicyclo[3.3.1]non-2-ene-9,4'-piperidine]. Structure of the products was studied using mass spectrometry, IR and NMR spectroscopy, as well as X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

This study presents an innovative method for synthesizing β‐amino carbonylated compounds, specifically 2‐[phenyl(phenylamino)methyl] cyclohexanone, achieving high conversions and diastereomeric ratios. Using trypsin or α‐chymotrypsin in both free and immobilized forms on titanate nanotubes (NtsTi), synthesized through alkaline hydrothermal methods, successful immobilization yields were attained. Notably, α‐chymotrypsin, when free, displayed a diastereoselective synthesis of the anti‐isomer with 97 % conversion and 16 : 84 (syn : anti) diastereomeric ratio, which slightly decreased upon immobilization on NtsTi. Trypsin, in its free form, exhibited diastereoselective recognition of the syn‐isomer, while immobilization on NtsTi (trypsin/NtsTi) led to an inversion of diastereomeric ratio. Both trypsin/NtsTi and α‐chymotrypsin/NtsTi demonstrated significant catalytic efficiency over five cycles. In conclusion, NtsTi serves as an effective support for trypsin and α‐chymotrypsin immobilization, presenting promising prospects for diastereoselective synthesis and potential industrial applications. Furthermore, it offers promising prospects for the diastereoselective synthesis of 2‐[phenyl(phenylamino)methyl] cyclohexanone through multicomponent Mannich reaction and future industrial application. [ABSTRACT FROM AUTHOR]

Although the wide variety of bioactivities of curcumin has been reported by researchers, the clinical application of curcumin is still limited due to its poor aqueous solubility. In view of this, a series of dimethylaminomethyl-substituted curcumin derivatives were designed and synthesized (compounds 1–15). Acetate of these derivatives were prepared (compounds 1a–15a). The Mannich reaction and aldol condensation reaction are the main reactions involved in this study. Compounds 6, 10, 12, 3a, 5a, 6a, 7a, 8a, 10a, 11a, 12a, 13a, 14a, and 15a exhibited better in vitro anti-inflammatory activity compared to curcumin in the RAW264.7 cell line. Compounds 5, 1a, 5a, 8a, and 12a exhibited better in vitro antioxidant activity compared to curcumin in the PC 12 cell line. Compounds 11, 13, 5a, 7a, and 13a exhibited better in vitro radiation protection compared to curcumin in the PC 12 cell line. The aqueous solubilities of all the curcumin derivative acetates were greatly improved compared to curcumin. [ABSTRACT FROM AUTHOR]

Two series of unsymmetrical hybrid benzoxazines were separately synthesized using combinations of natural bio-phenolic materials, namely cardanol (C) with eugenol (E), vanillin (V), and guaiacol (G) using diaminodiphenylmethane (ddm)/diaminodiphenyl ether (dde) through the well-known Mannich reaction. The synthesized hybrid benzoxazines have a cure temperature between 229 °C and 269 °C. Compared to previous synthesized benzoxazines, vanillin-based benzoxazines (C-dde-V and C-ddm-V) have a lower cure temperature. TGA results show that poly(C-ddm-V) and poly(C-dde-V), two hybrid polybenzoxazines, have superior thermal stability than the other hybrid polybenzoxazines. In order to develop polybenzoxazine composites, different wt% of GPTMS functionalized vermiculite was incorporated with poly(C-ddm-V). The properties of these composites were examined and contrasted with those of a neat matrix. The hybrid polybenzoxazines and composites water contact angle values vary from 136° to 144°, suggesting that all of the hybrid polybenzoxazines and composites have good hydrophobic behavior. On increasing the concentration of vermiculite, the dielectric constant value significantly decreased to a low dielectric constant. [ABSTRACT FROM AUTHOR]

Bispidine containing a paramagnetic group was obtained for the first time by the Mannich reaction using the 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO) free radical as a reagent. The structure of the target compound, tert-butyl 9-oxo-7-(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate, was confirmed by mass spectrometry and ESR spectroscopy, the molecular and crystal structure was established by X-ray diffraction analysis. In the synthesis of the starting 4-amino-TEMPO by the reductive amination reaction, the by-product of the further reaction of 4-amino-TEMPO with the starting ketone, the free biradical N-(2,2,6,6-tetramethyl-1-oxylpiperidin-4-yl)-2,2,6,6-tetramethyl-4-aminopiperidine-1-oxyl, was isolated and structurally characterized. [ABSTRACT FROM AUTHOR]

Marine anti-fouling coatings represent an efficient approach to prevent and control the marine biofouling. However, a significant amount of antifouling agent is added to improve the static antifouling performance of the coatings, which leads to an issue whereby static antifouling performance conflicts with eco-friendly traits. Herein, this work reports an in situ reduction synthesis of silver nanoparticles (AgNPs) within polymers to produce composite coatings, aiming to solve the aforementioned issue. Firstly, urushiol-based benzoxazine monomers were synthesized by the Mannich reaction, using an eco-friendly natural product urushiol and n-octylamine and paraformaldehyde as the reactants. Additionally, AgNPs were obtained through the employment of free radicals formed by phenolic hydroxyl groups in the urushiol-based benzoxazine monomers, achieved by the in situ reduction of silver nitrate in benzoxazine. Then, the urushiol-based benzoxazine/AgNPs composite coatings were prepared by the thermosetting method. AgNPs exhibit broad-spectrum and highly efficient antimicrobial properties, with a low risk to human health and a minimal environmental impact. The composite coating containing a small amount of AgNPs (≤1 wt%) exhibits effective inhibition against various types of bacteria and marine microalgae in static immersion, thereby displaying outstanding antifouling properties. This organic polymer and inorganic nanoparticle composite marine antifouling coating, with its simple preparation method and eco-friendliness, presents an effective solution to the conflict between static antifouling effectiveness and environmental sustainability in marine antifouling coatings. [ABSTRACT FROM AUTHOR]

Aromatic polyimides have attracted wide attentions in fields of aerospace, microelectronics and defense applications due to their outstanding thermal and mechanical performances. However, the rigidity originating from the imide structure attached with an aromatic ring causes difficulties in processing. In this study, we synthesized two ortho-phthalimide functional benzoxazine monomers with additional cross-linkable groups (including both furan and alkynyl). An ortho-phthalimide functional phenol, 2-(2-hydroxyphenyl) isoindole-1,3-dione (oPP), was obtained by reacting o-aminophenol and phthalic anhydride in acetic acid. Two monofunctional ortho-phthalimide containing benzoxazine monomers (oPP-fa and oPP-pa) were then synthesized using the Mannich reaction based on raw materials of oPP, furfurylamine/propargylamine and paraformaldehyde in toluene. The structures of benzoxazine monomers were confirmed by FT-IR and 1H NMR spectroscopies. We also investigated effects of cross-linkable functionalities on curing behaviors as well as their corresponding polymerization mechanisms. The activation energies of oPP-fa and oPP-pa were calculated by Kissinger and Ozawa equations based on DCS measurements with different heating rates. It demonstrates that the exothermic peak temperature of oPP-pa is located at 178.5 °C, which is much lower than that of oPP-fa (223.3 °C). The alkyne group in oPP-pa plays a catalytic effect role in reducing the ring-opening polymerization temperature of the oxazine ring. Moreover, the thermogravimetric analyzer (TGA) was used to evaluate thermal properties of the obtained polybenzoxazine thermosets. Both thermosets exhibited improved thermal stability compared with some other reported monobenzoxazine-derived polybenzoxazines. [ABSTRACT FROM AUTHOR]

A robust and practical difluoroalkylation synthon, α,α‐difluoroenol species, which generated in situ from trifluoromethyl diazo compounds and water in the presence of dirhodium complex, is disclosed. As compared to the presynthesized difluoroenoxysilane and in situ formed difluoroenolate under basic conditions, this difluoroenol intermediate displayed versatile reactivity, resulting in dramatically improved enantioselectivity under mild conditions. As demonstrated in catalytic asymmetric aldol reaction and Mannich reactions with ketones or imines in the presence of chiral organocatalysts, quinine‐derived urea, and chiral phosphoric acid (CPA), respectively, this relay catalysis strategy provides an effective platform for applying asymmetric fluorination chemistry. Moreover, this method features a novel 1,2‐difunctionalization process via installation of a carbonyl motif and an alkyl group on two vicinal carbons, which is a complementary protocol to the metal carbene gem‐difunctionalization reaction. [ABSTRACT FROM AUTHOR]

Manganese benzenesulfonate complex was synthesized under the condition of heating with manganese chloride and sodium benzenesulfonate as raw materials. The crystal of the complex was obtained by volatilizing solvent. The crystal structure was determined by single crystal X-ray diffraction technique and the molecular formula was [Mn (H2O)6] (C6H5 SO3)2. Powder X-ray diffraction proved that the target product had high phase purity. The molecular structure of the target product was verified by infrared spectroscopy. Thermogravimetric analysis showed that the target product had good thermal stability and did not decompose before 510 °C. The catalytic performance of manganese benzenesulfonate complex was investigated using Mannich reaction as a probe. The results showed that manganese benzenesulfonate could catalyze Mannich reaction with low dosage and high efficiency, and could still maintain catalytic activity after three repeated uses. Manganese benzenesulfonate complex showed good catalytic performance. [ABSTRACT FROM AUTHOR]

Introduction: The stem of the plant species Derris scandens (Roxb.) Benth. (DS) contains genistein‐7‐O‐[α‐rhamnopyranosyl‐(1→6)]‐β‐glucopyranoside (GTG), which is a unique marker. Previous analyses of GTG using antibody‐based immunoassays were compromised because of their high cross‐reactivity with structurally related compounds of DS, thereby limiting their applicability in DS quality control. Objective: Conjugation of GTG with carrier proteins was achieved using the Mannich reaction to produce a highly specific monoclonal antibody (mAb) targeting GTG (anti‐GTG mAb). Methods: The anti‐GTG mAb was generated using hybridoma technology and characterised using an indirect competitive enzyme‐linked immunosorbent assay (icELISA). Both lateral‐flow immunoassay (LFIA) and icELISA were developed to detect and quantify GTG in DS raw materials and associated products. Results: icELISA using the anti‐GTG mAb showed 100% specificity for GTG, with only 1.77% cross‐reactivity with genistin and less than 0.01% cross‐reactivity with other compounds. icELISA demonstrated a linear range for GTG determination between 62.5 and 2000 ng/mL. The limits of detection (LOD) and quantification were 49.68 and 62.50 ng/mL for GTG, respectively. The precision of the analysis ranged from 1.28% to 4.20% for repeatability and from 1.03% to 7.05% for reproducibility. The accuracy of the analysis ranged from 101.97% to 104.01% for GTG recovery. GTG levels determined via icELISA were consistent with those confirmed via high‐performance liquid chromatography (HPLC) (R2 = 0.9903). Moreover, the LOD of LFIA for GTG was 500 ng/mL. Conclusion: Immunoassays utilising specific anti‐GTG mAbs were successfully developed, including LFIA for rapid GTG detection and icELISA for GTG quantification. Derris scandens stem contains the phytochemical marker genistein‐7‐O‐[α‐rhamnopyranosyl‐(1 → 6)]‐β‐glucopyranoside (GTG). The Mannich reaction was used to conjugate GTG with carrier proteins for highly specific monoclonal antibody (mAb) production. Immunoassays using anti‐GTG mAbs were characterized and validated through indirect competitive enzyme‐linked immunosorbent assay (icELISA) and lateral flow immunoassay (LFIA). The highly specific mAb for GTG was used for GTG quantification via icELISA and rapid detection using LFIA. [ABSTRACT FROM AUTHOR]

In this study, a series of new carbazole derivatives were studied using several reactions, including the Vilsmeier–Haack reaction. A cyclization reaction within bromoacetic acid was reported to synthesize thiazolidinone compounds, followed by the Mannich reaction by reacting the prepared compound with formaldehyde and secondary amines, that is, diphenylamine, morpholine, and phthalimide. All synthesized compounds were characterized by infrared spectroscopy, liquid chromatography–mass spectrometry, and 1H and 13C nuclear magnetic resonance spectroscopy. The antioxidant activities of all prepared compounds were studied using the free-radical scavenging method using 2,2-diphenyl-1-picrylhydrazyl, demonstrating their moderate activity compared with ascorbic acid as the standard substance. The effectiveness of the prepared compounds as corrosion inhibitors was studied in an acidic medium of sulfuric acid (0.25 mol/L) using the electrochemical method. Acceptable corrosion-inhibition efficiency was achieved, with the highest inhibition rate of 55.21 % for compound VII.

We offer a new biogenetic proposal for the origin of the complex alkaloid alstonlarsine A, through rearrangement of the Strychnos alkaloids alstolucines B and F. Further, we provide evidence of the chemical feasibility of this proposal in the facile conversion of synthetic alstolucines into alstonlarsine A through a short, efficient sequence of N-methylation, β-elimination, and a cascade 1,7-hydride shift/Mannich cyclization. We believe that this is the first biogenetic proposal involving the tert-amino effect, a hydride-shift-based internal redox trigger of a Mannich cyclization. A further interesting feature of the cascade is that its stereochemical outcome most likely originates in conformational preferences during the hydride shift.

This article explores the synthesis and characterization of chejuenolides, a group of natural products with potential medicinal applications. The authors conducted total synthesis of chejuenolide C and identified it in a newly discovered strain of bacteria. They also investigated the stereochemistry involved in the macrocyclization process and found that the configuration at C13 has a significant impact on the stereochemistry of the product. The authors hope that their research will inspire further studies in biomimetic synthesis. [Extracted from the article]

The conversion of lignin into carbon dots is an emerging technology to make use of this renewable and abundant material. The low yield and low quantum yield of carbon dots from lignin remain key challenges of this technique. Here, prior amino modification of lignin using the Mannich reaction was proposed to improve carbon dot production from lignin by the hydrothermal method. Accordingly, the yield and quantum yield of carbon dots were synchronously improved from 9.8 wt% and 5.36% to 68 wt% and to 42.7%, respectively, because modified lignin suppresses hydrochar formation. A survey of the impact of the lignin structure on carbon dot production, and the structure and property relationship of the as-prepared carbon dots showed that the process could make use of condensed lignin to produce carbon dots with high performance. Techno-economic analysis suggested that this process noticeably reduced the product selling price because of the improved yield. This study provides a strategy to reduce the production cost of carbon dots from lignin, which may inspire the community to extract money out of lignin. [ABSTRACT FROM AUTHOR]

The aminated sodium lignosulfonate (AELS) was prepared through a Mannich reaction and characterized via FT-IR, TG, SEM and XPS in this study. Subsequently, the adsorption capacity of AELS for methyl blue (MB) was evaluated under various conditions such as pH, adsorbent dosage, contact time, initial concentration and temperature. The adsorption kinetics, isotherms and thermodynamics of AELS for methyl blue were investigated and analyzed. The results were found to closely adhere to the pseudo-second-order kinetic model and Langmuir isotherm model, suggesting a single-molecular-layer adsorption process. Notably, the maximum adsorption capacity of AELS for methyl blue (153.42 mg g−1) was achieved under the specified conditions (T = 298 K, MAELS = 0.01 g, pH = 6, VMB = 25 mL, C0 = 300 mg L−1). The adsorption process was determined to be spontaneous and endothermic. Following five adsorption cycles, the adsorption capacity exhibited a minimal reduction from 118.99 mg g−1 to 114.33 mg g−1, indicating good stability. This study contributes to the advancement of utilizing natural resources effectively and sustainably. [ABSTRACT FROM AUTHOR]

The current work explores the antioxidant and antimicrobial activity of a newly synthesized calix[4] arene acetanilide derivative (3), which was synthesized through Mannich reaction by the treatment of calix[4] arene with acetanilide, formaldehyde and acetic acid in tetrahydrofuran, The antioxidant activity was determined by using DPPH method. Results show that the new synthesized compound 3 has good antioxidant activity. The antimicrobial activity of 3 was staunched against different types of microorganisms, i.e. gram-negative and gram-positive bacterial strains (Escherichia Coli ATCC 8739 and Staphylococcus Aureus ATCC 10231) along with a fungus (Aspergillus Niger ATCC 16405). A suitable agar medium (Mueller Hinton agar) was applied for the growth of microorganisms. Kirby-Bauer well agar diffusion method was used to check the antimicrobial activity. The bacterial strains zone has been observed in between 250–4000 µg/ml. It is noticed that compound 3 has very good effect against fungus A niger as compared to bacterial strains. Its minimum inhibitory concentration (MIC) against A. niger, S. aureus and E. coli is found to be 250, 500 and 1000 µg/mL, respectively. Consequently, the study has been compared with the reported calix[4] arene derivatives and it has been revealed that the compound 3 is a good antimicrobial agent. Hence, it could be inferred that compound 3 is considerably effective against selected microorganisms and may be used as a medicine in near future and beneficial for the human. [ABSTRACT FROM AUTHOR]

Beta-aminocarbonyl compounds are important intermediates produced from Mannich condensation. In this research, benzaldehyde, para-hydroxy acetophenone or para-nitro acetophenone were reacted with a various of primary aromatic amines to give compounds (1-7) and (8-14), respectively. The chemical formulas of the synthesized compounds were confirmed by conducting some physical and spectroscopic measurements, such as, melting points, IR and H1-NMR spectrum. After testing the biological activity of some of the synthesized compounds (8,10,11,13) using Gram-positive (Streptococcus, and Staphylococcus aureus), Gram-negative (Klebsiella spp., and Escherichia coli) bacteria, as well as yeast strains, were chosen for this investigation (candidan albicans). Isolated bacteria were identified using standard methods of isolation and identification, including direct assays and culture on various media. Some theoretical tests have also been carried out such as SwissADME and cardioToxCSM prediction on all prepared compounds to predict their activity in terms of pharmacokinetic properties (ADME) and also predict their cardiotoxicity on some heart functions such as arrhythmia, cardiac failure, heart block, hERG toxicity, Hypertension (HT), and Myocardial Infarction (MI). [ABSTRACT FROM AUTHOR]

Obesity has become a serious global public health risk threatening millions of people. In this study, the astaxanthin–anthocyanin nanoparticles (AXT-ACN NPs) were used to investigate their effects on the lipid accumulation and antioxidative capacity of the high-sugar-diet-induced high-fat Caenorhabditis elegans (C. elegans). It can be found that the lifespan, motility, and reproductive capacity of the high-fat C. elegans were significantly decreased compared to the normal nematodes in the control group. However, treatment of high-fat C. elegans with AXT-ACN NPs resulted in a prolonged lifespan of 35 days, improved motility, and a 22.06% increase in total spawn production of the nematodes. Furthermore, AXT-ACN NPs were found to effectively extend the lifespan of high-fat C. elegans under heat and oxidative stress conditions. Oil-red O staining results also demonstrated that AXT-ACN NPs have a remarkable effect on reducing the fat accumulation in nematodes, compared with pure astaxanthin and anthocyanin nanoparticles. Additionally, AXT-ACN NPs can significantly decrease the accumulation of lipofuscin and the level of reactive oxygen species (ROS). The activities of antioxidant-related enzymes in nematodes were further measured, which revealed that the AXT-ACN NPs could increase the activities of catalase (CAT), superoxidase dismutase (SOD), and glutathione peroxidase (GSH-Px), and decrease the malondialdehyde (MDA) content. The astaxanthin and anthocyanin in AXT-ACN NPs showed sound synergistic antioxidation and lipid-lowering effects, making them potential components in functional foods. [ABSTRACT FROM AUTHOR]

In an attempt to make polybenzoxazines more sustainable, a novel bio-based benzoxazine monomer namely Q-Bz was synthetized via the Mannich condensation reaction utilizing Quercetin, paraformaldehyde and aniline. The chemical structure of the monomer was confirmed by 1H nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopies (FTIR). The curing behaviour was studied by differential scanning calorimetry (DSC) and the polymerization process was investigated by FTIR. The obtained results showed very low melting and polymerization temperatures (73 and 183°C, respectively) and the disappearance of the oxazine ring absorption bands due to the ring opening polymerization of the monomers. Afterwards, the cured bio-based thermoset, referred to as PQ-Bz, was obtained and its thermal stability and thermo-mechanical properties were also assessed by DSC and thermogravimetric analysis (TGA). As expected the newly developed thermoset exhibited high thermal stability along with excellent processability. Indeed, the results showed that PQ-Bz had a relatively high Tg of approximately 280°C, with a 53% char yield at 800°C, 5% and 10% weight reduction temperature (T5% and T10%) values of 349 and 373°C, respectively. These findings demonstrate the potential of the novel bio-based benzoxazine monomer as a sustainable alternative to traditional petroleum-based thermosets in high performance applications. [ABSTRACT FROM AUTHOR]

4-(2'-Oxo/thiobarbiturinyl acid)-2-(2"-halo-1"H-indolyl)-2,3-dihydro--1,5-benzothiazepines (7-10) and 4-(2'-oxo/thiobarbiturinyl acid)-2-(2"-halo-1"H-indolyl)-2,3-dihydro--1,5-benzoxazepines (11-14) undergoes Mannich reaction to afford compounds 4-(2'-oxo/thiobarbiturinyl acid)-2-(2"- halo-1"H-indolyl)-3-(substitutedphenyl aminomethylene)-2,3-dihydro-1,5-benzothiazepines (15-22) and 4-(2'-oxo/thiobarbiturinyl acid)-2-(2"-halo-1"H-indolyl)-3-( substitutedphenyl aminomethylene)- 2,3-dihydro-1,5-benzoxazepines (23-30) correspondingly. All the chemical framework of these newer drugs were elucidated by using elemental and IR and NMR spectroscopy. All these newly synthesized compounds were tested for antiepileptic effect against SMES experimental models and the results were collated with phenytoin sodium-standard drug. Results of antiepileptic profile showed promising effect in most of the derivatives synthesized. Activity equal to standard drug was shown by compounds 9 and 28. The most promising and active compound of this project was found to be 4-(2'- thiobarbiturinyl acid)-2-(2"-chloro-1"H-indolyl)-3-(chlorophenyl aminomethylene)-2,3-dihydro- 1,5-benzothiazepines, which elicited activity greater than the standard drug. All the antiepileptic drugs of the produced in this projects were also tested for ALD50. [ABSTRACT FROM AUTHOR]

A highly enantioselective Mannich reaction of biphenyl‐bridged seven‐membered cyclic N‐sulfonylimines with methyl alkyl ketones is disclosed in this study. The reaction was performed under organocatalysis by using a quinine‐derived primary amine as the catalyst in combination with a Brønsted acid as the co‐catalyst. High yields (up to 89 %) and excellent enantioselectivities (up to 97 % ee) were observed. For methyl alkyl ketones containing a larger alkyl substituent, specific regioselective addition to the C=N bond is favored at the methyl group. On the contrary, ketones containing a smaller alkyl substituent or hydroxyacetone substrates gave major syn selective Mannich products at the methylene group. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Different novel fused multicyclic iminosugars were synthesized from D‐ribose tosylate, aniline and vinyl ethyl ether by one‐pot three‐component stereoselective [4+2] reaction at different temperatures. The iminium‐ion is the key intermediate for the reaction. As a result, several complex fused iminosugars 3a were obtained by aza‐Diels‐Alder mechanism at 60 °C, while a series of aza‐C‐glycosides 5a were prepared by Mannich reaction at room temperature accompanied by another tetrahydroquinoline‐fused iminosugars 4a (tricyclic derivatives) through aza‐Diels‐Alder cycloaddition. This strategy will help to construct structurally diverse and bioactive iminosugar analogues. [ABSTRACT FROM AUTHOR]

Organophotocatalytic cascade cross-dehydrogenative-coupling/cyclization reaction of o-hydroxyarylenaminones with α-amino acid derivatives for the construction of α-chromone substituted α-amino acid derivatives was developed. Various N-arylglycine esters, amides and dipeptides underwent the cascade cyclization reaction well with o-hydroxyarylenaminones to afford the corresponding 3-aminoalkyl chromones in good to excellent yields. This approach consists of visible-light-promoted oxidation of α-amino acid derivatives, the Mannich reaction, and intramolecular nucleophilic cyclization under acidic conditions, and features a wide reaction scope, a simple operation and mild reaction conditions, which may have the potential to be used for the synthesis of bioactive molecules. [ABSTRACT FROM AUTHOR]

The increasing tendency to develop integration in electronic devices lead to the demand for thermally conductive polymeric materials. We offered a simple synthetic route to thermally conductive polybenzoxazine thermosets bearing liquid crystalline structures without the addition of any filler. Benzoxazine monomer of BZ-COOH was synthesized via Mannich reaction of p-hydroxy benzoic acid, p-formaldehyde, and dodecyl amine. After ring-opening polymerization of BZ-COOH, the obtained benzoxazine oligomer of OBZ-COOH was converted into acetoxy-bearing benzoxazine oligomer of OBZ-AC. Through self-crosslinking reaction of acetoxy group and carboxyl group in OBZ-AC using Zn(CH3COO)2 as a catalyst, the polybenzoxazine thermosets of OBZ-PES were produced. The liquid crystalline behavior of OBZ-AC was studied by POM, SAXS, and DSC. The results show that OBZ-AC formed the LC mesophase during isothermal and non-isothermal curing. The LC mesophase displays a layered arrangement of the smectic C phase. The formation mechanism is esterification reaction-induced. Owing to the formation of liquid crystalline structure, the TC of OBZ-PES is found to be 0.284 W/m. K, which is 21% and 16% greater than those of OBZ-COOH and OBZ-AC, respectively. In addition, the OBZ-PES shows excellent thermal performance. Its Tg(G") is up to 269°C. Its 5% weight loss temperature (Td5) and 10% weight loss temperature (Td10) are 383°C and 410°C, respectively. [ABSTRACT FROM AUTHOR]

A phosphine‐catalyzed (3+2) annulation of 4‐acetoxy allenoate and aldimine with the assistance of AgF is described. The success of this reaction hinges on the metathesis between the enolate‐phosphonium zwitterion and AgF, leading to a key intermediate comprising of silver enolate and a fluorophosphorane P(V)‐moiety. The former is able to undergo a Mannich reaction with aldimine, whereas the latter initiates a cascade sequence of AcO‐elimination/aza‐addition, thus furnishing the P(III)/P(V) catalysis. By taking advantage of the silver enolate, a preliminary attempt at an asymmetric variant was conducted with the combination of an achiral phosphine catalyst and a chiral bis(oxazolinyl)pyridine ligand (PyBox), giving moderate enantioselectivity. [ABSTRACT FROM AUTHOR]

We have designed and synthesized a series of bioinspired pyrano[2,3-f]coumarin-based Calanolide A analogs with anti-HIV activity. The design of these new calanolide analogs involved incorporating nitrogen heterocycles or aromatic groups in lieu of ring C, effectively mimicking and preserving their bioactive properties. Three directions for the synthesis were explored: reaction of 5-hydroxy-2,2-dimethyl-10-propyl-2H,8H-pyrano[2,3-f]chromen-8-one with (i) 1,2,4-triazines, (ii) sulfonylation followed by Suzuki cross-coupling with (het)aryl boronic acids, and (iii) aminomethylation by Mannich reaction. Antiviral assay of the synthesized compounds showed that compound 4 has moderate activity against HIV-1 on enzymes and poor activity on the cell model. A molecular docking study demonstrates a good correlation between in silico and in vitro HIV-1 reverse transcriptase (RT) activity of the compounds when docked to the nonnucleoside RT inhibitor binding site, and alternative binding modes of the considered analogs of Calanolide A were established. [ABSTRACT FROM AUTHOR]

Oleanolic and glycyrrhetic acids alkyne derivatives were synthesized as a result of propargylation of the indole NH‐group condensed with the triterpene A‐ring, the following aminomethylation led to a series of Mannich bases. The synthesized compounds were tested for their potential inhibition of influenza A/PuertoRico/8/34 (H1N1) virus in Madin‐Darby canine kidney (MDCK) cell culture and SARS‐CoV‐2 pseudovirus in baby hamster kidney‐21‐human angiotensin‐converting enzyme 2 (BHK‐21‐hACE2) cells. Mannich bases of oleanolic and glycyrrhetic acids N‐propargylated indoles 7, 8, and 12 were the most efficacious against influenza virus A with IC50 7–10 μM together with a low toxicity (CC50 > 145 μM) and high selectivity index SI value 20. Indolo‐oleanolic acid morpholine amide Mannich base holding N‐methylpiperazine moiety 9 showed anti‐SARS‐CoV‐2 pseudovirus activity with EC50 value of 14.8 μM. Molecular docking and dynamics modeling investigated the binding mode of the compounds 7 and 12 into the binding pocket of influenza A virus M2 protein and compound 9 into the RBD domain of SARS‐CoV‐2 spike glycoprotein. [ABSTRACT FROM AUTHOR]

Natural antibacterial agents exhibit tremendous potential in fabricating the durable antibacterial fabrics. Herein, natural pterostilbene (PL) was grafted onto chitosan (CS) through a Mannich reaction to obtain PLCS with high antibacterial activity. Furthermore, the durable antibacterial cotton fabric was fabricated using a layer-by-layer assembled coating with PLCS as the antibacterial agent. The results showed that at a molar ratio of PL to CS of 0.2:1 and a temperature of 80 ℃, PLCS with a grafting ratio of 17.3% achieved the lowest minimum inhibitory concentrations of 33.2 and 16.6 µg/mL against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively. Compared to those of CS and PL alone, the antibacterial activity of PLCS against S. aureus improved by 67.0% and 58.5%, while the activity against E. coli improved by 94.8% and 44.7%, respectively. The antibacterial rate of the PLCS cotton fabric against S. aureus and E. coli reached up to 99.9% after three assembled layers and maintained more than 80% after 20 washings. The PLCS antibacterial fabrics exhibited good wearing safety and wearing performances. [ABSTRACT FROM AUTHOR]

Esters of kynurenic acid, a known neuroprotective agent were reacted with cyclic amino acids to yield novel alkoxymethylated products under optimized reaction conditions. The importance of amino acid based (primary, secondary, biogenic and synthetic) organic additives was proven by the conduction of numerous test reactions. Thoroughly extended investigations, directly focusing on amino acid catalysis, which is an emerging and up-to-date field of catalysis and green chemical processes, have been conducted. The mechanism of the alkoxymethylation reaction was proposed and later the findings supported the hypothesis of the first retro-Mannich step (formation of the ortho-quinone methide intermediate) and subsequent formation of the alkoxymethylated derivatives. As a preparative result, two novel kynurenic acid derivatives bearing an alkoxymethyl moiety and two additional derivatives having amino acid residues at the site C-3 were synthesized, thus setting the scope and limitations of the modified Mannich reaction of kynurenic acid derivatives using amino acid nucleophiles. The mechanistic investigations highlighted the significant physicochemical effects of used nucleophiles on the amino-acid driven one-pot retro-Mannich initiated alkoxylation of kynurenic acid.