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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]

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]

Three‐component tandem Ritter and Mannich reactions were developed for one‐pot arylation and acyl protected amination of isatin. The acid catalyzed reaction produced wide variety of 3‐aryl‐3‐amidooxindoles directly from commercially available isatin. The C3 functionalization of isatin is affected by condensation with electron rich arenes and nitriles or amides with concomitant C−C and C−N bonds formation. Substituted isatins, different nucleophiles (cyclic and acyclic N, N‐disubstituted arylamines), aliphatic nitriles, and amides expanded the scope of the reaction. The reaction is simple, general, efficient and can switch the amidation substrate from nitriles in Ritter reaction to amides in Mannich reaction. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis of a novel amino triflamide catalyst and its application in enamine catalysis. The catalyst is derived from commercially available 1-nitropyrene and has a unique reactivity and selectivity. The synthesis of the catalyst involves several steps, but it offers a more efficient alternative to previously developed catalysts. The article also presents the results of several asymmetric reactions using the newly synthesized catalyst, demonstrating its utility in synthetic organic chemistry. [Extracted from the article]

Despite the continued efforts and advancements in anti‐cancer drug discovery, cancer is still considered as one of the leading causes of mortality globally. Hence, the discovery of novel chemotherapeutic agents that displayed a prominent effect against cancer is a pressing need. In this study, an expeditious cascade was used to access a pilot library of indolopyrazine fused to imidazole and pyrimidinone heterocyclic scaffolds. The synthetic strategy utilized a cascade reaction that combined Mannich with aza‐Michael addition reactions followed by coupling with a variety of amines. Phenotypic screening of the developed library against HCT116 colon and MCF‐7 breast cancer cell lines identified chemotypes that formed the basis for hit‐to‐lead development of anti‐cancer agents. The intriguing architecture and scope of functional variability of these types of pentacyclic molecules made them appropriate motifs for the development of lead drug candidates. [ABSTRACT FROM AUTHOR]

The indole motif plays a significant role in the quest for innovative drugs. As proposed, novel N‐substituted indole derivatives were synthesized, and their efficacy against bacteria and fungi was evaluated in vitro. The synthesis of these compounds was confirmed using easily accessible building blocks, and their structural formulas were supported by corrected analytical and spectroscopic analyses. Fresh strains of Candida albicans, Escherichia coli, and Pseudomonas aeruginosa, as well as Bacillus subtilis and Staphylococcus aureus, were utilized to assess the antibacterial and antifungal activities. Notably, the derivatives 1‐(phenyl (piperidine‐1‐yl) methyl)‐1H‐indole and 4‐(1H‐indol‐1‐yl) (phenyl) morpholine have strong antifungal effects on Candida albicans that are equivalent to those of the widely used drug fluconazole. [ABSTRACT FROM AUTHOR]

The development of advanced sustainable biomedical materials with superior biosafety and bioactivity for clinical applications is highly desirable. In the present investigation, biomass-based nanoparticles (NPs) were assembled through the Mannich reaction between the plant polyphenols and the broad-spectrum antibiotic tigecycline (TG). The fabricated NPs with uniform size demonstrated excellent oxidative balance effects, pH-responsive release properties and antibacterial performances. Furthermore, the intracellular and in vivo studies confirmed that the NPs are capable of reducing oxidative damage to cells and significantly repairing tissue injury in mice with peritonitis. This work presents an effective method and idea for constructing biomass-based materials for the treatment of infection-induced diseases. [ABSTRACT FROM AUTHOR]

Practical asymmetric synthesis of (S)-forphenicinol, the active ingredient of immunomodulator and anticancer drug Forfenimex®, from commercially available 2-hydroxy-dimethylterephthalate has been developed. Key steps of the synthesis are a stereogenic-center-forming enantioselective organocatalytic Mannich reaction of protected arylcarbaldimine with a kojic acid derivative and oxidative transformation of the γ-pyrone fragment into the carboxylic group. The total yield of (S)-forphenicinol hydrochloride (99% ee) via the proposed nine-step synthetic scheme (17%) is significantly higher than those attained by known methods (4.6% and 0.8%). [ABSTRACT FROM AUTHOR]

A method for concise and efficient synthesis of indazolo[2,3-a]quinazolines has been developed via a sequential annulation of 3-aminoindazoles and dehydrogenative aromatization of cyclohexanones. This high regioselectivity is attributed to the fact that the Mannich reaction is superior to the aldol reaction in this system. It is worth mentioning that this convenient process is successfully extended to 3-aminopyrazoles for assembling another class of medicinally prevalent pyrazolo[1,5-a]quinazolines. [ABSTRACT FROM AUTHOR]

The Mannich reaction is commonly used to introduce N atoms into compound molecules and is thus widely applied in drug synthesis. The Mannich reaction accounts for a certain proportion of structural modifications of natural products. The introduction of Mannich bases can significantly improve the activity, hydrophilicity, and medicinal properties of compounds; therefore, the Mannich reaction is widely used for the structural modification of natural products. In this paper, the application of the Mannich reaction to the structural modification of natural products is reviewed, providing a method for the structural modification of natural products. [ABSTRACT FROM AUTHOR]

α-Substituted-7-azaindoline amides and α,β-unsaturated 7-azaindoline amides have emerged as new versatile synthons for various metal-catalyzed and organic-catalyzed asymmetric reactions, which have attracted much attention from chemists. In this review, the progress of research on 7-azaindoline amides in the asymmetric aldol reaction, the Mannich reaction, the conjugate addition, the 1,3-dipole cycloaddition, the Michael/aldol cascade reaction, aminomethylation and the Michael addition-initiated ring-closure reaction is discussed. The α-substituted-7-azaindoline amides, as nucleophiles, are classified according to the type of α-substituted group, whereas the α,β-unsaturated 7-azaindoline amides, as electrophiles, are classified according to the type of reaction. [ABSTRACT FROM AUTHOR]

The study focuses on the synthesis of isatin- barbituric acid compounds through a two-step process. In the first step, using mannich reaction, new derivatives of Isatin are synthesized by reacting Isatin with either barbituric acid, along with formaldehyde. This reaction results in the formation of Isatin-barbituric acid derivative. In the second step, these Isatin derivatives are further reacted with various aniline derivatives to generate new compounds containing Isatin. Spectroscopic methods including FTIR, ¹H NMR, and 13C NMR are used to characterize the produced molecules. The study investigates the biological effects of several of the synthetic chemicals on certain bacterial strains, including Klebsiella pneumoniae and Staphylococcus aureus. The potential antibacterial activities of these substances are evaluated. [ABSTRACT FROM AUTHOR]

A simple and straightforward method is developed for the enantioselective synthesis of indol‐3‐yl‐piperidine. The reaction proceeds through a proline‐catalyzed direct Mannich reaction between glutaraldehyde and C3‐indolyl‐imines, followed by intramolecular reductive cyclization as an overall [4+2] annulation in one‐pot fashion. A series of indol‐3‐yl‐piperidine have been accessed with good yields up to 71 % and high enantioselectivity up to >99 % ee. [ABSTRACT FROM AUTHOR]

Nowadays, functionalized cucurbit[n]urils are considered one of the most important examples of macromolecules and have attracted a lot of attention due to their potential applications in several sectors. In the present work monomethyl‐cucurbit[7]uril (3) was synthesized for the first time through facile synthetic route with high purity form by the reaction of monomethylglycoluril (3a‐methyltetrahydroimidazo[4,5‐d]imidazole‐2,5(1H,3H)‐dione) with glycoluril (tetrahydroimidazo[4,5‐d]imidazole‐2,5(1H,3H)‐dione) in the ratio of 1:6, respectively, and formaldehyde in the presence of hydrochloric acid as a catalyst for 24 h at 95°C through Mannich reaction. Moreover, dimethyl‐cucurbit[7]uril (5) was successfully synthesized through the reaction of dimethylglycoluril (3a,6a‐dimethyltetrahydroimidazo[4,5‐d]imidazole‐2,5(1H,3H)‐dione) with glycoluril (tetrahydroimidazo[4,5‐d]imidazole‐2,5(1H,3H)‐dione), following the same procedure as for the monomethyl‐cucurbit[7]uril. The chemical structures of the obtained compounds were established by mass spectrometry, NMR spectroscopy, and quantum‐chemical calculations. [ABSTRACT FROM AUTHOR]

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A simple, mild and efficient method was proposed to construct fused tricyclic skeletons based on Mannich reaction. This work not only develops a new method to construct the tricyclic skeletons effectively, but also provides a new insight into the fused tricyclic skeletons containing flexible ring, which will greatly contribute to the research and development of the tricyclic energetic compounds. The relationship of structure-activity was studied by weak interactions calculation, single crystal structures analysis, electrostatic potentials calculation. The experimental and theoretical investigations suggest that the fused tricyclic skeleton containing flexible ring possesses better thermal stability and can be derivatized more easily compared with the similar aromatic fused tricyclic skeleton. Besides, the energetic derivates based on the fused tricyclic skeleton containing flexible ring possess good comprehensive properties: 2 (D ​= ​7726 ​m ​s−1, p ​= ​22.7 ​GPa) and 4 (D ​= ​8151 ​m ​s−1, p ​= ​26.3 ​GPa). All these results suggest that the fused tricyclic skeleton containing flexible ring is an ideal candidate to construct energetic compounds.

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.

Alkoxyalkylation and hydroxyalkylation methods utilizing oxo-compound derivatives such as aldehydes, acetals or acetylenes and various alcohols or water are widely used tools in preparative organic chemistry to synthesize bioactive compounds, biosensors, supramolecular compounds and petrochemicals. The syntheses of such molecules of broad relevance are facilitated by acid, base or heterogenous catalysis. However, degradation of the N-analogous Mannich bases are reported to yield alkoxyalkyl derivatives via the retro-Mannich reaction. The mutual derivative of all mentioned species are quinone methides, which are reported to form under both alkoxy- and aminoalkylative conditions and via the degradation of the Mannich-products. The aim of this review is to summarize the alkoxyalkylation (most commonly alkoxymethylation) of electron-rich arenes sorted by the methods of alkoxyalkylation (direct or via retro-Mannich reaction) and the substrate arenes, such as phenolic and derived carbocycles, heterocycles and the widely examined indole derivatives.

This review presents all currently known macroheterocyclic compounds that include a bispidine (3,7-diazabicyclo[3.3.1]nonane) fragment in their structure. A classification of bispidine-containing macroheterocycles, which is based on the ring size and the nature of bispidinic nitrogen atoms, is suggested. Synthetic approaches to the studied compounds are classified and considered. The features of the crystal structures and solution behavior of bispidine macroheterocycles are analyzed. Prospects for the development of these organic receptors are proposed.

Aim. To develop a preparative method for the synthesis of N-trimethylsilylimine of trifluoropyruvate, and study its interaction with acetone under organocatalytic conditions. Results and discussion. A simple preparative approach to the first representative of N-silylimines of trifluoropyruvate was developed based on the interaction of triphenylphosphinimide and trifluoropyruvic acid methyl ester by the aza-Wittig reaction. It was found that the addition of acetone to N-silylimine occurred in the presence of L- or D-proline and led to the formation of enantiomerically enriched α-amino-γ-oxocarboxylates. The hydrolysis of the ester function resulted in (R)-α-trifluoromethyl aminocarboxylic acid, and the cyclocondensation with isocyanates or 2,5-dimethoxytetrahydrofuran yielded nitrogen-containing heterocycles containing pyrimidine or pyrrolizine nuclei. Experimental part. The synthetic procedures for the N-silylimine of trifluoropyruvate and its reaction with acetone are provided, along with the transformations of obtained α-amino-γ-oxocarboxylates (hydrolysis, cyclocondensations with isocyanates and 2,5-dimethoxytetrahydrofuran). The structures of the compounds synthesized were proven by 1H, 13C, 19F NMR spectroscopy methods, as well as by the elemental analysis. Conclusions. A convenient method for the synthesis of N-silylimine of trifluoropyruvate has been developed. Using the example of the Mannich reaction with acetone, it has been demonstrated that N-silylimine of trifluoropyruvate is a convenient substrate for the synthesis of optically active 3,3,3-trifluoroalanine derivatives.

The Mannich reaction is commonly used to introduce N atoms into compound molecules and is thus widely applied in drug synthesis. The Mannich reaction accounts for a certain proportion of structural modifications of natural products. The introduction of Mannich bases can significantly improve the activity, hydrophilicity, and medicinal properties of compounds; therefore, the Mannich reaction is widely used for the structural modification of natural products. In this paper, the application of the Mannich reaction to the structural modification of natural products is reviewed, providing a method for the structural modification of natural products.

The total synthesis of (−)-δ-lycorane is reported. We performed organocatalytic Mannich reaction between phenylacetaldehyde and γ-hydroxy lactam to construct a 5-substituted-2-pyrrolidone derivative in favor of the cis-isomer. Furthermore, diastereoselective conjugate addition to α,β-unsaturated lactam was accomplished to obtain 4,5-disubstituted-2-pyrrolidone. The other salient features of this synthesis include Bischler–Napieralski reaction and ring closing metathesis. [ABSTRACT FROM AUTHOR]

L-Pro was previously used as an organocatalyst in the Mannich reaction under homogeneous conditions; a recoverable catalyst could be useful; this is the first report on the application of prolinated carbon dots to the Mannich reaction. Prolinated carbon dots were synthesized electrochemically using a bottom-up approach; they were characterized and used in the Mannich reaction in water using only a slight excess of ketone; for a useful comparison, L-proline decorated graphene oxide was synthesized. The characterization of carbon dots and functionalized graphene oxide confirmed the presence of L-Pro on their surface; their use in the Mannich reaction gave good yields when carrying out the reaction in water; a possible recycle of the catalyst was demonstrated. Both electrochemically synthesized prolinated carbon dots and prolinated graphene oxide acted as organocatalysts in the Mannich reaction. Higher yields were obtained using L-Pro-CDs obtained under galvanostatic conditions. [ABSTRACT FROM AUTHOR]

In the development of research on studying the reactivity of quinopimaric acid, aminomethylation proceeding chemoselectively at position 3 of the carbon backbone was carried out. [ABSTRACT FROM AUTHOR]

NO gas therapy is a supplementary approach for tumor treatment due to the advantages of minimal invasion, little drug resistance, low side effect and amplified efficacy. l -Arginine (L-Arg), a natural NO source with good biocompatibility, can release NO under the stimulation of H 2 O 2 in tumor microenvironment. However, the conventional l -Arg delivery systems via noncovalent loading usually lead to inevitable premature leakage of nano-cargos during blood circulation. In this work, an efficient l -Arg self-delivery supramolecular nanodrug (SDSND) for tumor treatment is demonstrated by combining Mannich reaction and π-π stacking. l -Arg links to (-)-epigallocatechin gallate (EGCG) with the assistance of formaldehyde through Mannich reaction, and then assembles into nanometer-sized particles via π-π stacking. The guanidine group of l -Arg and the phenolic hydroxyl groups of EGCG are preserved in the SDSNDs, which allows for accomplishing gas therapy by provoking tumor cell apoptosis and combining with EGCG to amplify apoptosis, respectively. In addition, the SDSNDs exhibit high biocompatibility and avoid the premature leakage of l -Arg in blood circulation, providing an alternative l -Arg delivery system for NO gas therapy. NO gas therapy has attracted emerging interest in tumor treatment. However, the controlled NO release and the avoidance of premature leakage of NO donors remain challenging. In this work, L-Arginine (L-Arg) self-delivery supramolecular nanodrug for efficient tumor therapy is demonstrated through the Mannich reaction of L-Arg, (-)-epigallocatechin gallate (EGCG) and formaldehyde. Stimulated by tumor microenvironment, the guanidine groups of L-Arg allow for accomplishing NO release and thus provoking tumor cell apoptosis. The nanodrug also avoids the premature leakage of L-Arg in blood circulation. Moreover, the preserved phenolic hydroxyl groups of EGCG combine with L-Arg to amplify apoptosis. The nanodrug exhibits high biocompatibility and good therapeutic effect, providing an alternative L-Arg delivery system for NO gas therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Direct enantioselective synthesis of 2‐substituted chromen‐4‐ones, bearing the amino group at α‐stereogenic center with respect to the heterocycle is developed. It is based on Mannich‐type asymmetric addition of 3‐hydroxychromen‐4‐one and its analogues to N‐protected imines in the presence of available alkaloid dihydrocuprein. α‐Stereogenic chromenone amino derivatives were formed in this reactions in 81–95% yield with up to 98% ee. The chiral adducts were transformed to diverse enantiomerically enriched chromen‐4‐one functional derivatives. [ABSTRACT FROM AUTHOR]

Sarpagine alkaloids offer signicant opportunities in drug discovery, yet the efficient total syntheses and diverse structural modifications of these natural products remain highly challenging due to the architectural complexity. Here we show a homo-Mannich reaction of cyclopropanol with imines generated via a Bischler-Napieralski reaction enables a protecting-group-free, redox economic, four-step access to the tetracyclic sarpagine core from L-tryptophan esters. Based on this advancement, diversified syntheses of sarpagine alkaloids and analogues are achieved in a short synthetic route. The systematic anticancer evaluation indicates that natural products vellosimine and Na-methyl vellosimine possess modest anticancer activity. Intensive structural optimization of these lead molecules and exploration of the structure−activity relationship lead to the identification of analogue 15ai with an allene unit showing a tenfold improvement in anticancer activities. Further mechanism studies indicate compound 15ai exertes antiproliferation effects by inducing ferroptosis, which is an appealing non-apoptotic cell death form that may provide new solutions in future cancer therapies. The Mannich reaction is a well-established method for the synthesis of β-amino carbonyl compounds while the analogous reactions of homo-enol or its equivalents with imines or iminium ions are much less explored. Here, the authors describe a homo-Mannich reaction of cyclopropanol with imines generated via a Bischler-Napieralski reaction. [ABSTRACT FROM AUTHOR]

Gold‐catalyzed cascade reactions between 1,5‐diyn‐3‐ols and nitrones to deliver carbazole derivatives are described. Such cascade reactions are applicable to facile synthesis of polyaromatic compounds containing carbazole subunits. Notably, the reaction mechanism involves unexpected oxoarylations, rather than oxidative Mannich reactions as known for but‐1‐yn‐4‐ols. Our control experiments indicate that the presence of a second alkyne as in 1,5‐diyn‐3‐ols enables such oxoarylations due to a weak bonding between gold and this alkyne, rending the tethered alcohol less conformationally flexible. [ABSTRACT FROM AUTHOR]

Diazo compounds are rare natural products possessing various biological activities. Kinamycin and lomaiviticin, two diazo natural products featured by the diazobenzofluorene core, exhibit exceptional potency as chemotherapeutic agents. Despite the extensive studies on their biosynthetic gene clusters and the assembly of their polyketide scaffolds, the formation of the characteristic diazo group remains elusive. l-Glutamylhydrazine was recently shown to be the hydrazine donor in kinamycin biosynthesis, however, the mechanism for the installation of the hydrazine group onto the kinamycin scaffold is still unclear. Here we describe an O-methyltransferase-like protein, AlpH, which is responsible for the hydrazine incorporation in kinamycin biosynthesis. AlpH catalyses a unique SAM-independent coupling of l-glutamylhydrazine and polyketide intermediate via a rare Mannich reaction in polyketide biosynthesis. Our discovery expands the catalytic diversity of O-methyltransferase-like enzymes and lays a strong foundation for the discovery and development of novel diazo natural products through genome mining and synthetic biology. Diazo compounds, such as kinamycin, are rare bioactive natural products whose assembly has been extensively studied, but the formation of the diazo group is elusive. Here, the authors report O-methyltransferase-like protein, AlpH, which is responsible for the l-glutamylhydrazine incorporation in kinamycin biosynthesis. [ABSTRACT FROM AUTHOR]

Cyanuric chloride, a chlorinated analog of 1,3,5‐triazine, is used as a catalyst, promoter, and activator to catalyze and initiate several reactions like Beckmann rearrangement, Lossen rearrangement, Biginelli reaction, Suzuki coupling reaction, Pictet Spengler reaction, Mannich reaction, etc. It is employed in several reactions due to its several properties like stable, non‐volatile, cost‐efficient, easy to handle, and easy commercial availability. Moreover, it is a very renowned precursor for the synthesis of triazine‐class pesticide atrazine, dyes, and crosslinking agents. Herein in this review article, the reactions initiated, catalyzed, and promoted by cyanuric chloride from 2010 to 2022 have been elaborated. [ABSTRACT FROM AUTHOR]

In this work, by utilizing 6 mol% of 1,3‐bis(carboxymethyl)imidazolium chloride [BCMIM][Cl] ionic liquid as a catalyst, a highly effective diastereoselective one‐pot multicomponent Mannich reaction has been established. The three components, namely, cyclohexanone, substituted aromatic aldehydes, and substituted aromatic amines, underwent the Mannich reaction efficiently under the solvent‐free condition at room temperature in the presence of 6 mol% [BCMIM][Cl] catalyst to afford the desired β‐amino ketones. Excellent diastereoselectivity, rapid reaction times, high yields, and no purification by column chromatography are the key characteristics of this process. All synthesized derivatives were thoroughly characterized and confirmed using 1H NMR, 13C NMR, and Fourier‐transform infrared spectral methods. Moreover, the catalytic activity of the [BCMIM][Cl] ionic liquid catalyst was maintained after being reprocessed and used three times. [ABSTRACT FROM AUTHOR]

This review presents all currently known macroheterocyclic compounds that include a bispidine (3,7-diazabicyclo[3.3.1]nonane) fragment in their structure. A classification of bispidine-containing macroheterocycles, which is based on the ring size and the nature of bispidinic nitrogen atoms, is suggested. Synthetic approaches to the studied compounds are classified and considered. The features of the crystal structures and solution behavior of bispidine macroheterocycles are analyzed. Prospects for the development of these organic receptors are proposed. [ABSTRACT FROM AUTHOR]

The title compound, C20H21F3N2O4, features a main twelve-membered difuryl ring with which the furan rings make dihedral angles of 76.14 (5) and 33.81 (5)°. The dihedral angle between the furan rings is 42.55 (7)°. The six-membered nitrogen heterocycle has a twist-boat conformation. In the crystal, pairs of molecules are connected by intermolecular C—H...O interactions, generating an R22(14) ring motif. These pairs of molecules form zigzag chains along the a-axis direction by means of C—H...F interactions. Furthermore, C—H...π and C–F...π interactions link the molecules into chains along the b-axis direction, forming sheets parallel to the (001) plane. These sheets are also connected by van der Waals interactions.

Mannich‐type reactions involving alkylzinc reagents have been developed using different strategies. We show that the addition of these organometallic species to sulfonyl imines occurs upon simple heating and affords Mannich products in moderate to excellent yields (14 examples, 30–99 %). Interestingly, N‐alkyl imines were also found to be suitable partners after activation as an acyliminium by acetyl chloride (12 examples, 49–86 %) or, more originally, by TMSCl (14 examples, 26–87 %). These methods proved complementary, leading to the preparation of both N‐protected secondary or tertiary amines and N‐unprotected secondary amines in good yields, with an increased eco‐compatibility, and under simple conditions. [ABSTRACT FROM AUTHOR]

Using oleanolic acid as a starting compound, a series of new oleanane-type triterpenic derivatives were synthesized via O-acylation (with nicotinic, isonicotinic, and methoxycinnamic acid acyl chlorides), N-amidation (with cyclic- or polyamines), the Mannich reaction (with secondary cyclic amines), and Claisen–Schmidt condensation (with aromatic aldehydes), and their potencies as treatments for immunometabolic disorders were investigated. The compounds were evaluated against α-glucosidase and PTP1B enzymes and LPS-stimulated murine macrophages. It was found that the target compounds are highly effective α-glucosidase inhibitors but lack activity against PTP1B. A leading compound, N-methylpiperazine methylated 2,3-indolo-oleanolic propargyl amide 15, is also a micromolar inhibitor of NO synthesis in LPS-stimulated macrophages and suppresses oxidative bursts in neutrophils with similar efficiency. These results, in addition to its ability to stimulate glucose uptake in rat fibroblasts and improve maltose tolerance in rats, allow us to consider compound 15 a promising prototype drug for the treatment of immunometabolic defects in type 2 diabetes. [ABSTRACT FROM AUTHOR]

A pyrrolidine‐catalyzed three‐component reaction of azlactone, N,O‐acetal and alcohol for the synthesis of α,β‐diamino ester was reported. The N,O‐acetal served as the imine equivalent to occur Mannich reaction with azlactone, and the in situ generated α‐functionalized azlactone subsequently underwent a ring‐opening process in the presence of alcohol. A series of α,β‐diamino esters were obtained in 36–99% yields under mild reaction conditions. The product could be synthesized on gram‐scale and transformed into the α,β‐diamino acid. [ABSTRACT FROM AUTHOR]

Aminated lignin (AL) was obtained by modifying technical lignin (TL) with the Mannich reaction, and aminated lignin-based titanate nanotubes (AL-TiNTs) were successfully prepared based on the AL by a facile hydrothermal synthesis method. The characterization of AL-TiNTs showed that a Ti–O bond was introduced into the AL, and the layered and nanotubular structure was formed in the fabrication of the nanotubes. Results showed that the specific surface area increased significantly from 5.9 m2/g (TL) to 188.51 m2/g (AL-TiNTs), indicating the successful modification of TL. The AL-TiNTs quickly adsorbed 86.22% of Cr(VI) in 10 min, with 99.80% removal efficiency after equilibration. Under visible light, AL-TiNTs adsorbed and reduced Cr(VI) in one step, the Cr(III) production rate was 29.76%, and the amount of total chromium (Cr) removal by AL-TiNTs was 90.0 mg/g. AL-TiNTs showed excellent adsorption capacities of Zn2+ (63.78 mg/g), Cd2+ (59.20 mg/g), and Cu2+ (66.35 mg/g). After four cycles, the adsorption capacity of AL-TiNTs still exceeded 40 mg/g. AL-TiNTs showed a high Cr(VI) removal efficiency of 95.86% in simulated wastewater, suggesting a promising practical application in heavy metal removal from wastewater. [ABSTRACT FROM AUTHOR]

The acid dyes and reactive dyes are most commonly used in silk dyeing and printing. The weak forces such as hydrogen bonds, ion bonds and Van der Waals forces between acid dyes and silk exist, leading to the poor color fastness for wet treatment. Although reactive dyes can be covalently bonded with silk to obtain higher color fastness for wet treatment, they need to be fixed on silk under high temperature and alkaline conditions, and there are also problems such as large salt consumption and low dye utilization. Therefore, we proposed the chemical modification of the tyrosine side chain in silk fibroin by using dyes containing aromatic primary amine to achieve reactive dyeing on silk fibers. According to the theory of Mannich reaction, with aldehydes as bridge, dyes containing aromatic primary amine can react with silk tyrosine residues to form C—C—N covalent bond, which can be regarded as a reactive coloration of dyes containing aromatic primary amine on silk fibers. In this method, silk can obtain higher color depth value under low temperature and acidic conditions, and has also ideal color fastness to washing and rubbing. In this study, the commercial C. I. Reactive Orange 13 was modified to achieve a dye M Orange 13 containing aromatic primary amine group synthesized by using the active Cl atom on the reactive group of the original dye. Then, the traditional formula of reactive dyes and the three-component Mannich reaction formula of the dye containing aromatic primary amine were employed to screen printing of silk fabrics. The coloration performances of the two dyes and their printing formulas with the low-temperature fixing process were studied. Moreover, compared with the conventional printing of silk fabrics with high-temperature steaming, the differences of the two dyes and processes were evaluated by measuring the color depth value K/S and fixation rate of printed silk fabrics, and the effect of parameters such as temperature and time of low-temperature fixation process on the printing performance of the synthesized dye containing aromatic primary amine was analyzed. The results showed that the temperature for fixation with low-temperature and wet state had a certain effect on the K/S value of printed silk fabrics using conventional reactive dyes and the dye containing aromatic primary amine in a Mannich reaction. For conventional reactive dye formula, a higher K/S value of printing silk fabrics could be obtained with low-temperature and wet state process for 3 hours at 60 ℃, which was slightly lower than that of the steaming process commonly used. The dye containing aromatic primary amine based on Mannich reaction and the conventional reactive dye obtained quite similar K/S values on their printing silk fabrics with the same fixation of low-temperature and wet state process, and their color fastness of washing and rubbing all reached 4 grades or more. Therefore, the dye containing aromatic primary amine based on Mannich reaction could be applied for for high color fastness printing of silk fabrics with the fixation process of low-temperature and wet state without alkali. In conclusion, dyes containing aromatic primary amine could be synthesized by modification of commercial reactive dyes. The silk fabrics could be processed with low-temperature and wet state without alkali after printing and the Mannich reaction happened to achieve a good color depth value, and comparatively high color fastness of washing and rubbing. The results provide a new way for energy-saving and environmentally friendly printing methods of silk fabrics. [ABSTRACT FROM AUTHOR]

The title compound, systematic name 4,4',6,6'-tetrachloro-2,2'-{[(2-methoxy-ethyl)azanediyl]bis(methylene)}diphenol (C17H17Cl4NO, 1), was prepared via a modified Mannich reaction between 2-meth-oxy-ethyl-amine, 2,4-dichlorophenol, and aqueous formaldehyde. The resulting amine bis(phenol) provides an interesting comparison to related species as a result of the electron-withdrawing substituents on the phenol rings, in combination with similar steric parameters. One of the Cl atoms was modeled as a two-component disorder with partial occupancies of 0.49 (3) and 0.51 (3), while the pendant ether group was modeled as a two-component disorder with partial occupancies of 0.867 (3) and 0.133 (3). A comparison of metrical parameters for the title compound and closely related structures provides insight into the use of these species as ligands to support transition-metal complexes for applications as homogeneous catalysts. [ABSTRACT FROM AUTHOR]

Tetrakis(l,3-dihydrobenzoxazine) calix[4]resorcinarenes 4–6 were synthesized via the Mannich reaction from the corresponding resorcin[4]arenes 1–3 with S-(−)-α-methylbenzylamine or R-(+)-α-methylbenzylamine and formaldehyde (aq.). The products were well characterized by FT-IR, 1H NMR, 13C NMR spectroscopies and single crystal X-ray diffraction analysis. Molecular structures of compounds 4, 5 and 6 showed the same R/S configuration to the starting amines. Compounds 4–6 are stabilized by a collar of intramolecular hydrogen bonding networks between the hydroxy groups and the oxygens from the benzoxazine rings. Compounds 4 and 5 could encapsulate the guest molecules of acetone and dichloromethane, respectively. The UV and 1H NMR titration experiments were performed to study the host-guest chemistry between compound 4 and small acetone molecules, indicating that compound 4 exhibited encapsulation behavior towards acetone molecules through hydrogen bonding interactions. [ABSTRACT FROM AUTHOR]

Ethylenediamine bridged benzoxazine proligands were synthesized by a modified Mannich condensation reaction. The reaction of the proligands with two equivalents of AlMe3 resulted in the formation of dinuclear Al(III) compounds in high yield and purity. When the ligand binds to the Al(III) center, it forms two separate six‐membered N,O‐chelates with the two Al atoms that resembles the N‐alkylated salan moiety. Each aluminum atom adopts a distorted tetrahedral geometry as revealed from the single‐crystal X‐ray diffraction studies of 1. The catalytic activity of these aluminum compounds was investigated towards the ROP of rac‐LA and ROCOP of epoxides (PO, CHO, tBuGE) and phthalic anhydride and ROCOP of CHO with CO2. These aluminum compounds showed notable catalytic activity towards the ROP and ROCOP reactions in the absence of cocatalyst. [ABSTRACT FROM AUTHOR]

In this study, a new class of energetic green benzoxazine polymers is introduced based on vanillin, as a renewable reactant. The newly developed monomers were afforded by the reaction of vanillin with exploshores groups bearing compounds, namely the 2,4 dinitrophenylhydrazine and the para-nitroaniline, respectively, following the typical Mannich reaction. The chemical structure and the formation of the oxazine ring of both monomers were confirmed by 1H and 13C NMR, FTIR, and elemental analysis. The ring opening polymerization mechanism was investigated by FTIR and DSC-TGA analyses. The energetic performances, as well as the physicochemical properties, were studied by a bomb calorimeter, deflagration tester, and electronic densimeter. Overall, both polymers showed promising energetic performances with deflagration temperatures of about 275 and 261°C for the 2,4 dinitrophenylhydrazine and para-nitroaniline-based polybenzoxazines, respectively. The thermal analysis results highlighted that these polymers can be effectively used as reactive structure materials (RSMs) owing to their combination of high thermal stability above operational temperatures and remarkable energetic performances. [ABSTRACT FROM AUTHOR]

A series of novel Mannich bases were designed, synthesized, and screened for their antimicrobial activity. The target compounds were synthesized from 4-(3-chlorophenyl)-5-(3-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione and different piperazine derivatives. The structures of the products were confirmed by 1H and 13C NMR and elemental analysis. The activity of piperazine derivatives against bacteria (Gram-positive: Staphylococcus epidermidis, Staphylococcus aureus, Micrococcus luteus, Bacillus cereus, and Bacillus subtilis; Gram-negative: Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Proteus mirabilis) and yeasts (Candida glabrata, Candida krusei, and Candida parapsilosis) was determined by the minimum inhibitory concentration and minimum bactericidal concentration values. Significant activity was observed against Gram-positive bacteria, mainly staphylococci (PG7–PG8) and bacteria of the genes of Micrococcus and Bacillus (PG1-3), as well as selected strains of Gram-negative bacteria, including bacteria of the Enterobacteriaceae family (PG7), while all tested compounds showed high fungistatic activity against Candida spp. yeasts, especially C. parapsilosis, with MICs ranging from 0.49 µg/mL (PG7) to 0.98 µg/mL (PG8) and 62.5 µg/mL (PG1-3). In conclusion, the results obtained confirm the multidirectional antimicrobial activity of the newly synthesized piperazine derivatives. Furthermore, in silico studies suggest that the tested compounds are likely to have good oral bioavailability. The results obtained will provide valuable data for further research into this interesting group of compounds. The library of compounds obtained is still the subject of pharmacological research aimed at finding new interesting biologically active compounds. [ABSTRACT FROM AUTHOR]

The reaction of (1-ethoxyethylidene)malononitrile with cyanoacetamide or cyanothioacetamide has yielded 6-amino-4-methyl-2-(thio)oxo-1,2-dihydropyridine-3,5-dicarbonitriles. The resulting pyridine derivatives enter into the aminomethylation reaction with an excess of formaldehyde and primary amines with the formation of previously unknown 8-methyl-6-oxo-3-R-1,3,4,6-tetrahydro-2H-pyrido[1,2-a][1,3,5]triazine-7,9-dicarbonitriles. Further treatment of 6-amino-4-methyl-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile and its oxygen analog with excess of formaldehyde has led to the formation of 3,10-dimethyl-1,8-dithioxo-5,6,12,13-tetrahydro-1H,8H-dipyrido[1,2-a:1′,2′-e][1,3,5,7]tetrazocin-2,4,9,11-tetracarbonitrile and 6,6′-[methylenedi(imino)]bis(4-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile), respectively. These compounds have shown a pronounced antidote effect against the herbicide 2,4-D (2,4-dichlorophenoxyacetic acid) in laboratory and field experiments on sunflower seedlings. Furthermore, 6-amino-4-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile has exhibited pronounced anticorrosion properties, acting as an adsorption-type corrosion inhibitor. The mechanism of the anticorrosion action has been investigated in detail using X-ray photoelectron spectroscopy. [ABSTRACT FROM AUTHOR]

The proposed article relates to synthesis and the study of new propargyl ester derivatives, and biostimulation activity of 4-(bis(2- hydroxyethyl)amino)but-2-yn-1-yl butyrate. Aminomethylation reactions of the obtained propargyl ester with ethanolamine and paraform were carried out in the presence of a catalyst. Copper salts were used as a catalyst. The structure of the new propargyl ester derivatives was established by IR and ¹H-, 13C- NMR spectroscopy. Comparative tests show that the test derivative of the drug 4-(bis(2- hydroxyethyl)amino)but-2-yn-1-yl butyrate showed a higher growth-promoting activity. [ABSTRACT FROM AUTHOR]