Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• , inspired by natural alkaloids such as deoxyvasicinone and evodiamine with promising inhibition of ChEs and antioxidant and neuroprotective effects against glutamate-induced OS in HT-22 cells [41]. In 2016, Dgachi et al. [42] applied a Knoevenagel-based multicomponent approach to further explore the

• a multicomponent approach. Bucherer–Bergs reaction: The dense presence of mGlu2/3 receptors in regions associated with psychiatric disorders suggests them as potential drug targets. One clinical candidate to treat psychiatric disorders was the mGluR2/3 agonist pomaglumetad methionil (POM). This drug

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• study commenced with synthesizing a series of 1,5-disubstituted tetrazole-methanesulfonylindoles 18a–n, achieved through a high-order multicomponent approach. This strategy, similar to that previously reported by our research group for synthesizing the 1,5-disubstituted tetrazole-benzofuran bis

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• purification. Thus, it significantly improves existing approaches. Keywords: catalysis; deazaalloxazine; flavin; multicomponent approach; one-pot reaction; Introduction Heterocyclic compounds containing pyrimidine and quinoline motifs in their structure, both of natural and synthetic origin, find a wide set

Morita–Baylis–Hillman reaction of 3-formyl-9H-pyrido[3,4-b]indoles and fluorescence studies of the products

• Nisha Devi and
• Virender Singh

Beilstein J. Org. Chem. 2022, 18, 926–934, doi:10.3762/bjoc.18.92

• -3 position. Our group has previously explored 1-formyl-β-carbolines and 3-formyl-β-carbolines for the generation of β-carboline-imidazo[1,2-a]azine conjugates at C-1 as well as C-3 position by the application of the Groebke–Blackburn–Bienaymé (GBB) multicomponent approach [46][47]. Our research

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• potential rearrangement explained the regioselectivity during ring closure as depicted in Scheme 44. Theoretically, two regioisomeric pairs of adenine (115, A) and isoadenine are possible (C, D) (Scheme 44). However, using the multicomponent approach one product, 4-amino-7-arylimidazo[1,2-a][1,3,5]triazines

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• reaction; Introduction A multicomponent approach towards the synthesis of the desired product offers a number of advantages over a stepwise method. Such advantages include the development of a design that is: cheaper, simpler, economical, and environmentally friendly [1][2]. Multicomponent reactions are

In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines

• Irina G. Tkachenko,
• Sergey A. Komykhov,
• Vladimir I. Musatov,
• Svitlana V. Shishkina,
• Viktoriya V. Dyakonenko,
• Vladimir N. Shvets,
• Mikhail V. Diachkov,
• Valentyn A. Chebanov and
• Sergey M. Desenko

Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231

• multicomponent approach to minimize the number of reaction steps according to green chemistry principles as well. Based on our recent research [26][27][28], where water proved to be an effective solvent for the multicomponent synthesis of low-molecular-mass dihydroazolopyrimidines, we decided to use water also

One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion

• Christina Görgen,
• Katharina Boden,
• Guido J. Reiss,
• Walter Frank and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 1360–1370, doi:10.3762/bjoc.15.136

• ] specifically have been published employing a cyclizing addition of an acylhydrazone to the carbonyl group as a ring-forming reaction [32][33][34][35][36][37][38][39][40], their diversity-oriented one-pot synthesis in a multicomponent approach has remained unexplored to date. In the course of our program

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• has been demonstrated by Alonso et. al. [26] with the development of a multicomponent approach to obtain 4-azasteroids using an intramolecular Ugi-4CR between a bifunctional steroidal ketoacid and different amines and isocyanides. Because of the poor reactivity of the steroidal ketone, the Ugi-4CR had

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• employ a three-component, diastereoselective variant of the Ugi reaction for the synthesis of a prolyl pseudo-peptide catalyst, which proved effective in an organocatalytic conjugate addition reaction [6]. Later, our groups developed an Ugi reaction-based multicomponent approach enabling the structure

• diversification of prolyl pseudo-peptide catalysts [7], which also proved great efficacy in organocatalytic asymmetric Michael reactions. As extension of this concept to the field of immobilized organocatalysts, we reported the use of the multicomponent approach for the synthesis of silica-grafted peptide

• . We have previously proven the feasibility of this multicomponent approach for the combinatorial synthesis and rapid screening of pseudo-peptide catalysts [7] and their silica gel-immobilized variants [8]. The choice of using acetone and the S-configured α-methylbenzylamine was made in agreement with

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• one (path A), decarboxylative coupling to form intermediates 14 and 15, followed by a cyclization take place, while in the second path (B), the first step seems to be the formation of amide 16. Indeed, another multicomponent approach to isoindolinones uses iodobenzamides 17 as starting materials

• improvement on this multicomponent approach, making use of β-cyclodextrine as promoter, water as a solvent, and microwave heating (route C, Scheme 16) [98]. Under these neutral conditions, they prepared up to nineteen compounds (60–95%, R1 = H, Cl, R2 = alkyl, benzyl, aryl), including two derivatives

• ranging from 66 to 92% was prepared. The mechanism is presumably very similar to that of the above reaction (Scheme 17), where isobenzofuranone 61 plays the role of formylbenzoic acid 33. Another multicomponent approach to isoindoloquinazolinones 57 is the palladium-catalysed reaction of 2-aminoamides 59

Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines

• Ramana Sreenivasa Rao and
• Chinnasamy Ramaraj Ramanathan

Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46

• . Results and Discussion Piperazine-2,6-diones are usually synthesized through an Ugi [30] multicomponent approach. The condensation of primary amines with benzyliminodiacetic acid at high temperatures or CDI/THF at reflux leads also to the formation of piperazine-2,6-diones (Scheme 1). Using CDI/THF under

Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively

• Marcel Mirel Popa,
• Emilian Georgescu,
• Mino R. Caira,
• Florentina Georgescu,
• Constantin Draghici,
• Raluca Stan,
• Calin Deleanu and
• Florea Dumitrascu

Beilstein J. Org. Chem. 2015, 11, 1079–1088, doi:10.3762/bjoc.11.121

• reactions taking place at the nitrogen atom in the pyridine moiety compared to 4-(2-pyridyl)pyrimidine (6). The reactions were carried out via a multicomponent approach by mixing all the starting materials in 1,2-epoxybutane under reflux. In some cases the isolation and characterization of the intermediate

• other possible indolizine (14A) was observed also in the bulk reaction mass in low to medium quantities but was not recovered, further work being in progress to investigate this aspect. Due to the fact that the salts 13 are not easy to work up we ran the reaction in a multicomponent approach and only in

• salts were not easily purified and we preferred the multicomponent approach. However, we isolated and characterized the bromides 15a,b (Table 3). The new 7-(pyrimidyl)indolizines were obtained in moderate to good yields and were characterized by NMR spectroscopy. The 1H NMR spectra of the bromides 15

Multicomponent versus domino reactions: One-pot free-radical synthesis of β-amino-ethers and β-amino-alcohols

• Bianca Rossi,
• Nadia Pastori,
• Simona Prosperini and
• Carlo Punta

Beilstein J. Org. Chem. 2015, 11, 66–73, doi:10.3762/bjoc.11.10

• the results of our in depth investigation to allow for the one-pot multicomponent addition of alcohols and ethers to ketimines generated in situ, by inhibition of the domino reaction. Results and Discussion The optimization of the multicomponent approach was conducted by the one-pot assembly of p

• to the field clearly illustrate how the free-radical approach can be considered a valuable alternative to classical ionic protocols [16][17][18][19][20][21][22][23]. In this context, we succeeded in combining the advantages of the radical synthetic route with the high added value of a multicomponent

• approach. In fact, our procedure requires neither the preformation of imines nor anhydrous media, due to the coordinating effect of titanium salts, which promote the one-pot synthesis of amino derivatives according to a classical MCR. The basic approach consists of the simple mixing of an aniline, an

The Ugi four-component reaction as a concise modular synthetic tool for photo-induced electron transfer donor-anthraquinone dyads

• Sarah Bay,
• Gamall Makhloufi,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 1006–1016, doi:10.3762/bjoc.10.100

• Ugi 4CR, a quick semiquantitative estimation of the feasibility of the charge-separated state based upon inexpensive analytical methods is highly desirable. Here we present the synthetic versatility of this multicomponent approach to Do–anthraquinone dyads, as exemplified by phenothiazinyl and

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• ], the CB1 receptor of cannabinoid and fatty acid amide hydrolase [114][118][119][120][121]. In this context, Hulme and co-workers described a Passerini multicomponent approach towards cis-constrained norstatine mimics, a class of HIV-1 protease inhibitors with a tetrazole core (Scheme 45) [122]. They

• several pharmaceutical compounds such as antipsychotics, anticonvulsants, local anaesthetics or analgesics [131]. An interesting diastereoselective multicomponent approach towards such six-membered pipecolic acid-based analogues was described by Maison et al. [128] Although this work is closely related to

The multicomponent approach to N-methyl peptides: total synthesis of antibacterial (–)-viridic acid and analogues

• Ricardo A. W. Neves Filho,
• Sebastian Stark,
• Bernhard Westermann and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2012, 8, 2085–2090, doi:10.3762/bjoc.8.234

• synthesis of the N-terminal dipeptide 3, amino acid 9 was coupled with benzyl glycinate in the presence of ethyl chloroformate to give 10 in 88% yield. This intermediate was hydrogenated to afford the dipeptide acid 3 quantitatively. An alternative multicomponent approach to dipeptide 3 requires the use of

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• , and the best results were obtained when Pd/C–PPh3 was used as the catalyst system (Scheme 22). Another attractive palladium-mediated multicomponent approach towards the synthesis of indole derivatives involving the cyclization of a 2-alkynylaniline intermediate is based on a sequential, site-selective

Multicomponent synthesis of artificial nucleases and their RNase and DNase activity

• Anton V. Gulevich,
• Lyudmila S. Koroleva,
• Olga V. Morozova,
• Valentina N. Bakhvalova,
• Vladimir N. Silnikov and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2011, 7, 1135–1140, doi:10.3762/bjoc.7.131

• RNA in RPMI 1640 and in H2O, respectively; 8 and 9 - compound 5d incubated with RNA in RPMI 1640 and in H2O, respectively. Multicomponent approach to target molecules. Synthesis of starting diisocyanides 3a–3e. Synthesis of new aRNAses. Conditions: a. RCHO (3 eqiuv), BnNH2 (3 equiv), PhP(OH)2 (1 equiv