Article
Chemistry, Organic
Marine Pinaud, Leila Vaitilingom, Gayathiri Gnanalingam, Tania Xavier, Erwan Le Gall, Marc Presset
Summary: The use of N-alkyl imines in decarboxylative Mannich reaction with substituted malonic acids half oxyesters (SMAHOs) has been developed to afford a direct access to secondary beta(2,3)-aminoesters. The transformation occurs under very practical conditions (DABCO as a catalyst in bulk toluene and open to air) and can be performed with a broad range of each substrate in yields of 36 to 97 %. Importantly, the reaction was found to require the use of acidic additives in combination with the organocatalyst to limit the competitive olefination reaction.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Philip J. Chevis, Chi Bong Eric Chao, Christopher Richardson, Christopher Hyland, Richmond Lee, Stephen G. Pyne
Summary: The crotylation reactions of chiral α-F, α-OBz and α-OH aldehydes were carried out under Petasis-borono-Mannich conditions using (E)- or (Z)-crotylboronates and primary amines. The reactions resulted in γ-addition products with high diastereoselectivity and enantioselectivity. The stereochemical outcomes of the reactions could be explained using transition state models and were supported by DFT calculations. Representative products were transformed into highly functionalized 1,2,3,6-tetrahydropyridines and 3H-oxazolo[3,4-a]pyridine-3-ones, which are valuable scaffolds in synthesis.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Review
Chemistry, Multidisciplinary
Subhankar Biswas, Nimisha Bania, Subhas Chandra Pan
Summary: Intermolecular cross Rauhut-Currier reactions have gained significant attention in recent years due to their ability to produce complex structures with good regio- and stereo- selectivity using various catalysts. This review highlights the recent developments in these reactions, involving both achiral and chiral catalysts, resulting in products with diverse utilities. Furthermore, detailed mechanistic studies of these reactions are also presented.
Article
Chemistry, Multidisciplinary
Wei Liu, Tianren Qin, Wansen Xie, Jinmiao Zhou, Zidan Ye, Xiaoyu Yang
Summary: We have developed an efficient modular asymmetric synthesis of azahelicenes from readily available polycyclic aromatic amines, aldehydes, and (di)enamides, employing a central-to-helical chirality conversion strategy. A series of aza[5]- and aza[4]helicenes bearing various substituents were easily obtained with good yields and high enantioselectivities. The diverse derivatizations and the preliminary application of the azahelicene derivative as a chiral organocatalyst demonstrated the potential of this method, and the photophysical and chiroptical properties of these azahelicenes were well studied, showing potential applications in novel organic optoelectronic materials.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
William R. R. Cassels, Evan T. T. Crawford, Jeffrey S. S. Johnson
Summary: We report a simple catalytic crystallization-driven enantio- and diastereoselective Mannich reaction for the synthesis of stereodefined alpha-monosubstituted-ss-ketoesters, dissymmetric ss-diesters, dissymmetric ss-diketones, and ss-keto amides. This method efficiently leverages product epimerization in solution. Mechanistic studies suggest that the initial enantioselective, diastereodivergent skeletal assembly is catalyzed by a chiral tertiary amine organocatalyst, followed by crystallization-induced diastereoconvergence to provide the challenging alpha-stereocenter in excellent stereoselectivity.
Review
Chemistry, Multidisciplinary
Huiting Lv, Yongli Du, Haibin Zhang, Yong Zheng, Zhijia Yan, Ning Dong
Summary: Mannich-type reactions utilize active alpha-H compounds, amines, and aldehydes to synthesize valuable beta-aminocarbonyl compounds. The yield, selectivity, and regioselectivity of the reaction are influenced by catalysts and the structural characteristics of the substrates. This article summarizes the developments in symmetric and asymmetric Mannich-type reactions according to the type of substrates and analyzes the factors affecting reaction outcomes.
Article
Chemistry, Physical
Jeffrey S. Johnson, William R. Cassels, Evan T. Crawford
Summary: A simple catalytic crystallization-driven enantio- and diastereoselective Mannich reaction was disclosed for the synthesis of stereodefined alpha-monosubstituted-keto esters, dissymmetric diesters, dissymmetric diketones, and keto amides that productively leveraged product epimerization in solution. Mechanistic studies suggested that the initial enantioselective, diastereodivergent skeletal assembly was catalyzed by a chiral tertiary amine organocatalyst, which then facilitated second stage crystallization-induced diastereoconvergence to provide the challenging alpha-stereocenter in excellent stereoselectivity.
Review
Biochemistry & Molecular Biology
Minoo Dabiri, Noushin Farajinia Lehi, Reza Mohammadian
Summary: Fluoro-organic compounds have attracted significant interest for their role in developing new bioactive materials and healthcare products. Catalytic Mannich reaction allows for the synthesis of versatile amine synthons, opening clear paths for the synthesis of natural product and pharmaceutical molecules. This review highlights the use of catalytic asymmetric Mannich reactions in the synthesis of fluorine-containing amine compounds and discusses possible distinct mechanisms.
MOLECULAR DIVERSITY
(2022)
Article
Biochemistry & Molecular Biology
Regina Westphal, Eclair Venturini Filho, Laiza Bruzadelle Loureiro, Claudio Francisco Tormena, Claudia Pessoa, Celina de Jesus Guimaraes, Mariana Palmeira Manso, Rodolfo Goetze Fiorot, Vinicius Rangel Campos, Jackson Antonio Lamounier Camargos Resende, Fabrizio Medici, Sandro Jose Greco
Summary: In this study, a microwave-assisted Knoevenagel/Michael/cyclization multicomponent domino methodology was developed for the synthesis of spiro compounds. Twelve spiro compounds were synthesized and one of them exhibited anti-cancer activity.
Article
Chemistry, Organic
Fuka Hori, Tomoyuki Yoshimura, Jun-ichi Matsuo
Summary: A novel method for the synthesis of 3-alkyl-2-arylindoles was developed through sequential oxidation and reduction reactions. Starting from 2-(2-nitrophenyl)ethanols prepared by a base-catalyzed three-component reaction, the desired products were obtained by oxidation and reduction steps. Notably, a selective synthesis of N-hydroxyindole was also achieved. Furthermore, the highly nucleophilic nature of transient benzylic anions in DMSO was demonstrated for the three-component reactions.
Article
Chemistry, Applied
Sandor Balazs Kiraly, Laszlo Toth, Tibor Kovacs, Attila Benyei, Erika Lisztes, Balazs Istvan Toth, Tamas Biro, Attila Kiss-Szikszai, Katalin E. E. Kover, Attila Mandi, Tibor Kurtan
Summary: Four series of chiral condensed heterocycles, representing four novel skeletons and exhibiting antiproliferative activity, were synthesized through Domino Knoevenagel-cyclization reactions of 2H-chromene and chroman derivatives containing o-formylaryl amine or ether side-chain. The cyclization occurred through four different mechanisms: a concerted intramolecular hetero Diels-Alder reaction (IMHDA), a stepwise polar [2+2] cycloaddition, a [1,5]-hydride shift-6-endo cyclization, or a multi-step nitro hetero Diels-Alder-ring-opening-Cadogan-type cyclization sequence. The latter reaction provided a novel route to hydroxyindoles through an inverse Cadogan-type cyclization, where the nitro group is deoxygenated by a nitro IMHDA-ring-opening sequence. The cyclization mechanisms and stereoselectivity were studied using DFT calculations, which allowed for proposing a mechanism for the multi-step cyclization to hydroxyindoles and explaining the observed diastereoselectivity.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Mohammad A. Alam
Summary: Recent advances in the synthesis of thiazole compounds using domino/cascade and multicomponent approaches have been summarized in this perspective.
CURRENT ORGANIC CHEMISTRY
(2022)
Article
Polymer Science
Fusun Seyma Gungor
Summary: A compound with a phenolic group was successfully synthesized and subjected to Mannich reactions with primary amine compounds and paraformaldehyde, resulting in three thermally polymerizable naphthoxazines with high yields. The structures of the exchange products were characterized using analytical techniques and the ring-opening polymerization behavior was investigated.
EUROPEAN POLYMER JOURNAL
(2023)
Article
Chemistry, Applied
I-Ting Chen, Ren-You Guan, Jeng-Liang Han
Summary: In this study, a catalytic asymmetric vinylogous Mannich/annulation/acylation reaction was developed for the synthesis of chiral spiro-oxindole piperidine derivatives with polyaromatic scaffolds. The reaction provided the desired products in good yields and high enantioselectivity. DFT computational calculations were used to explain the mechanism and origin of the observed enantioselectivity and O-acetylated products.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Applied
Amit Shikari, Koushik Mandal, Deepak Chopra, Subhas Chandra Pan
Summary: A new organocatalytic asymmetric synthesis method has been developed for the synthesis of cyclic acetals with a spirooxindole skeleton. It was found that a bifunctional squaramide catalyst with an adamantyl motif was the most effective in the cascade reaction, providing high diastereo- and enantioselectivities for the desired products.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Organic
Jorge Gomez-Carpintero, J. Domingo Sanchez, J. Francisco Gonzalez, J. Carlos Menendez
Summary: Ball milling of various esters with ethanol and calcium nitride successfully afforded primary amides, maintaining the integrity of a stereocenter alpha to carbonyl. This method was also applied to the synthesis of rufinamide, showing compatibility with different functional groups.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
J. Carlos Menendez
Summary: The treatment of COVID-19 requires pharmacological intervention targeting both the viral infection and inflammatory stages. Antiviral drugs can target viral proteins and host proteins, with the latter having the advantage of being effective against all variants of the virus. In addition, drugs targeting the hyperinflammatory phase of the disease, such as JAK kinases inhibitors and anti-inflammatory corticosteroids, are also important strategies.
Review
Chemistry, Organic
Jose Clerigue, M. Teresa Ramos, J. Carlos Menendez
Summary: Catalytic asymmetric Povarov protocols have experienced explosive growth in the past decade, focusing on the use of chiral Lewis and Bronsted acids, as well as strategies involving hydrogen bond formation and covalent aminocatalysis. Recent variations, such as the nitroso Povarov reaction and interrupted Povarov reactions, are also discussed as alternative routes to chiral scaffolds beyond tetrahydroquinolines.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Angel Cores, Noelia Carmona-Zafra, Olmo Martin-Camara, Juan Domingo Sanchez, Pablo Duarte, Mercedes Villacampa, Paloma Bermejo-Bescos, Sagrario Martin-Aragon, Rafael Leon, J. Carlos Menendez
Summary: Curcumin analogues with the fragment of piperlongumine showed broad-spectrum activity in the treatment of Alzheimer's disease, with good absorption, antioxidant properties, and the ability to inhibit inflammation.
Article
Biochemistry & Molecular Biology
Angel Cores, Patrycja Michalska, Jose Miguel Perez, Enrique Crisman, Clara Gomez, Mercedes Villacampa, Jose Carlos Menendez, Rafael Leon
Summary: This study synthesized hybrids combining the antioxidant and NRF2 induction properties of lipoic acid with the neuroprotective activity of CGP37157. The compounds showed a good neuroprotective profile against oxidative stress and hyperphosphorylation, as well as significant anti-neuroinflammatory activity.
Article
Chemistry, Analytical
Victor Gonzalez-Ruiz, Angel Cores, M. Mar Caja, Vellaisamy Sridharan, Mercedes Villacampa, M. Antonia Martin, Ana Olives, J. Carlos Menendez
Summary: The fluorescence properties and anion-binding response of newly synthesised carbazole derivatives were studied, and potential anion sensors were designed. 1-hydroxycarbazole proved to be a sensitive fluorescent sensor for fluoride and chloride anions through hydrogen bond interactions.
Article
Chemistry, Organic
Giammarco Tenti, Jose Clerigue, M. Teresa Ramos, J. Carlos Menendez
Summary: A five-step route to synthesizing a ring-contracted analogue of the oxicam derivative propoxicam from thiosalicylic acid, sarcosine, and N,N-dimethyl-1,3-propanediamine is described. Key steps include the base-promoted cross-Claisen coupling reaction, installation of a beta-ketoamide moiety, and a Hg(II)-induced cyclization.
Article
Biochemistry & Molecular Biology
Lucia Perez-Regidor, Joan Guzman-Caldentey, Nils Oberhauser, Carmen Punzon, Balazs Balogh, Jose R. Pedro, Eva Falomir, Alessandra Nurisso, Peter Matyus, J. Carlos Menendez, Belen de Andres, Manuel Fresno, Sonsoles Martin-Santamaria
Summary: In this study, a computer-aided drug repurposing approach was used to virtually screen and discover novel TLR4 modulators with a non-lipopolysaccharide-like structure. After screening thousands of approved drugs and drug-like molecules, several compounds with TLR4 antagonist activity were identified through biological assays. This collaborative work expands the chemical diversity for the inspiration of new classes of TLR4 modulators.
Article
Chemistry, Organic
Miriam Ruiz-Serrano, Pilar Lopez-Alvarado, J. Carlos Menendez
Summary: Researchers found that the reaction between an a-formylcyclohexanone derivative and tosyl azide, in the presence of rhodium trifluoroacetate dimer, produced an acylsulfonamide derivative. This transformation is proposed to occur through a domino mechanism involving the in situ generation of an a-diazoketone, which is then transformed into a rhodium carbenoid and combined with N-tosylformamide, a side product of the first step. Overall, this transformation results in the formation of a C-N bond between the formyl carbon and the azide nitrogen adjacent to the sulfonyl group.
Article
Chemistry, Organic
Angel Cores, Mercedes Villacampa, J. Carlos Menendez
Summary: The microwave-assisted reaction of 2-nitroimidazole with 3-bromophenacyl bromide in the presence of potassium carbonate as a base and dimethylformamide as a solvent afforded 2-(3-bromophenyl)imidazo[2,1-b]oxazole. The formation of this compound was explained via a domino mechanism comprising an initial N-alkylation reaction of the imidazole substrate, followed by the base-promoted deprotonation of the position adjacent to the carbonyl to give an enolate anion that finally cyclizes via an intramolecular SNAr reaction, with the loss of the nitro group as potassium nitrite. Then, the proposed 1-(3-bromophenacyl)-2-nitroimidazole intermediate could be isolated by reducing the reaction time and was shown to be a precursor of the imidazo[2,1-b]oxazole final product.
Review
Chemistry, Medicinal
Alvaro Sarabia-Vallejo, Pilar Lopez-Alvarado, J. Carlos Menendez
Summary: Alzheimer's Disease (AD) is a challenging health issue, particularly in developed countries, due to increasing prevalence and economic burden. Previous efforts to discover new diagnostic and therapeutic tools have failed, highlighting the need for new approaches. Theranostic agents have emerged as promising tools for AD research and personalized medicine, providing diagnostic information and therapeutic activity simultaneously. This review emphasizes the positive impact that theranostics can have in the future clinical practice.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Diksha Rajput, Gowsia Jan, Muthu Karuppasamy, Nattamai Bhuvanesh, Subbiah Nagarajan, C. Uma Maheswari, J. Carlos Menendez, Vellaisamy Sridharan
Summary: An efficient cascade annulation reaction using secondary amine catalyst was developed for the synthesis of functionalized 2H-chromenes and 1,2-dihydroquinolines with a p-quinone methide scaffold. The microwave-assisted strategy achieved high yields and completion of reactions in just 15 min. The synthesized products were further transformed into valuable compounds via a palladium-catalyzed double C-H bond activation process and epoxidation.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Damiano Rocchi, Juan F. Gonzalez, Olmo Martin-Camara, Maria Grazia Perrone, Morena Miciaccia, Antonio Scilimati, Celine Decouty-Perez, Esther Parada, Javier Egea, J. Carlos Menendez
Summary: This study found that m-terphenylamine derivatives are selective inhibitors of cyclooxygenase-1 (COX-1), able to block microglia inflammatory response and elicit a neuroprotective effect.
Review
Pharmacology & Pharmacy
Alvaro Sarabia-Vallejo, Maria del Mar Caja, Ana I. Olives, M. Antonia Martin, J. Carlos Menendez
Summary: Many active pharmaceutical ingredients have low oral bioavailability due to factors such as poor solubility and physical and chemical instability. The formation of inclusion complexes with cyclodextrins can improve the oral bioavailability of many drugs. The microencapsulation process can modify key properties of the included drugs. Examples of stabilizing labile drugs and increasing the bioavailability of class IV drugs through inclusion complex formation are discussed. The stabilization and improvement in nutraceuticals used as food supplements is also considered. Cyclodextrin-based nanofibers lead to significant bioavailability enhancements. The synthesis of chemically modified cyclodextrins, polymers, and nanosponges based on cyclodextrins is discussed, as well as analytical techniques for characterizing inclusion complexes.
Review
Biochemistry & Molecular Biology
Angel Cores, Noelia Carmona-Zafra, Jose Clerigue, Mercedes Villacampa, J. Carlos Menendez
Summary: Quinones can be both cytoprotective and cytotoxic in the treatment of neurodegenerative diseases due to their modification of biomolecules. Low doses of electrophilic quinones activate the Keap1/Nrf2 pathway and induce the expression of detoxifying enzymes. Natural quinones like coenzyme Q(10) and its analogues have neuroprotective effects relevant to Alzheimer's and Parkinson's diseases. Other endogenous and non-endogenous quinones with neuroprotective activities are also discussed.
Article
Chemistry, Organic
Fuying Zhu, Yamei Lin
Summary: In this study, a low-metal iron-supported catalyst (Fe20/NC-Mg) was reported for the efficient synthesis of quinoxaline compounds, using water as a solvent and without additional bases. The synergistic effect of FeNx site and Mg (OH)2 nanorods in the catalyst played a key role in achieving high yields (82-91%) in 16 examples. The gram-level synthesis and reusability of the catalysts after four cycles demonstrated its industrial application potential.
Article
Chemistry, Organic
Mikhail Kozlov, Alexey Tyurin, Andrey Dmitrenok, Vyacheslav Rusak, Aleksander Fedorov, Igor Zavarzin, Yulia Volkova
Summary: This study presents a novel and practical synthesis method for phosphorus-substituted 1,3,4-thiadiazolines using phosphorylthioformic acid hydrazides and ketones. The protocol demonstrates operational simplicity, availability of reagents, and tolerance towards different functional groups.
Article
Chemistry, Organic
Jisna Jose, Thomas Mathew
Summary: 2-Cyclopentenone and its derivatives are highly esteemed synthetic intermediates with exceptional utility in organic synthesis. They are favored structural motifs in numerous pharmaceutical drugs and natural products, highlighting their significance. The review discusses the various methods used to synthesize cyclopentenones from 2016 to 2023.