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  • Review
  • Open Access
18 Citations
8,870 Views
20 Pages

The 115 Years Old Multicomponent Bargellini Reaction: Perspectives and New Applications

  • Marta Serafini,
  • Ilaria Murgia,
  • Mariateresa Giustiniano,
  • Tracey Pirali and
  • Gian Cesare Tron

21 January 2021

Despite its uniqueness, the Bargellini multicomponent reaction remains barely known by the most part of chemists. This can be ascribed to the fact that this transformation has not been adequately reviewed in the classic books of named reactions in or...

  • Article
  • Open Access
417 Views
13 Pages

Multicomponent Reaction for the Synthesis of β-Ketosulfides in Deep Eutectic Solvents

  • Chiara Falcini,
  • David Jaén-Herrera,
  • Rosario Fernández,
  • Andrés R. Alcántara and
  • Gonzalo de Gonzalo

22 February 2026

The use of Type III Deep Eutectic Solvents (DESs) as both solvents and cocatalysts enable the one-pot synthesis of several β-ketosulfides, structural motifs commonly found in biologically active compounds, via a multicomponent reaction (MCR) inv...

  • Article
  • Open Access
13 Citations
2,422 Views
17 Pages

16 April 2023

A microwave-promoted multicomponent reaction of isatins, α-amino acids and 1,4-dihydro-1,4-epoxynaphthalene is achieved under environmentally friendly conditions, delivering oxygen-bridged spirooxindoles within 15 min in good to excellent yield...

  • Communication
  • Open Access
24 Citations
4,691 Views
11 Pages

A Brønsted Acid-Catalyzed Multicomponent Reaction for the Synthesis of Highly Functionalized γ-Lactam Derivatives

  • Xabier del Corte,
  • Edorta Martinez de Marigorta,
  • Francisco Palacios and
  • Javier Vicario

14 August 2019

Brønsted acids catalyze a multicomponent reaction of benzaldehyde with amines and diethyl acetylenedicarboxylate to afford highly functionalized γ-lactam derivatives. The reaction consists of a Mannich reaction of an enamine to an imine,...

  • Article
  • Open Access
17 Citations
7,637 Views
13 Pages

19 October 2011

We have recently reported a novel multicomponent reaction between arylacetic acids and isocyanides, affording α-acyloxyacrylamides through an unusual mechanism. The products of this novel multicomponent reaction can rearrange to five membered heteroc...

  • Article
  • Open Access
5 Citations
3,032 Views
17 Pages

Novel 5-Nitrofuran-Tagged Imidazo-Fused Azines and Azoles Amenable by the Groebke–Blackburn–Bienaymé Multicomponent Reaction: Activity Profile against ESKAPE Pathogens and Mycobacteria

  • Alexander Sapegin,
  • Elizaveta Rogacheva,
  • Lyudmila Kraeva,
  • Maxim Gureev,
  • Marine Dogonadze,
  • Tatiana Vinogradova,
  • Petr Yablonsky,
  • Saeed Balalaie,
  • Sergey V. Baykov and
  • Mikhail Krasavin

A chemically diverse set of 13 5-nitrofuran-tagged heterocyclic compounds has been prepared via the Groebke–Blackburn–Bienaymé multicomponent reaction. The testing of these compounds against the so-called ESKAPE panel of pathogens...

  • Review
  • Open Access
109 Citations
9,768 Views
28 Pages

Multicomponent Reaction-Assisted Drug Discovery: A Time- and Cost-Effective Green Approach Speeding Up Identification and Optimization of Anticancer Drugs

  • Giovanni Graziano,
  • Angela Stefanachi,
  • Marialessandra Contino,
  • Rubén Prieto-Díaz,
  • Alessia Ligresti,
  • Poulami Kumar,
  • Antonio Scilimati,
  • Eddy Sotelo and
  • Francesco Leonetti

Multicomponent reactions (MCRs) have emerged as a powerful strategy in synthetic organic chemistry due to their widespread applications in drug discovery and development. MCRs are flexible transformations in which three or more substrates react to fo...

  • Article
  • Open Access
18 Citations
3,109 Views
19 Pages

19 January 2023

Dioxidovanadium(V) complex [VVO2(sal-aebmz)] (1) (where Hsal-aebmz = Schiff base derived from the condensation of salicylaldehyde and 2-aminoethylbenzimidazole) has been immobilized on chloromethylated polystyrene (PS-Cl) cross-linked with divinylben...

  • Review
  • Open Access
16 Citations
7,404 Views
48 Pages

1 December 2020

Drug discovery efforts largely depend on access to structural diversity. Multicomponent reactions allow for time-efficient chemical transformations and provide advanced intermediates with three or four points of diversification for further expansion...

  • Review
  • Open Access
5 Citations
4,928 Views
20 Pages

Multicomponent reactions (MCR) have been used to synthesize a wide range of analogs from several classes of heterocyclic compounds, with multifaceted medicinal uses. The synthesis of highly functionalized molecules in a single pot is a unique propert...

  • Review
  • Open Access
19 Citations
6,067 Views
19 Pages

Bio-Catalysis in Multicomponent Reactions

  • Ndze Denis Jumbam and
  • Wayiza Masamba

15 December 2020

Enzyme catalysis is a very active research area in organic chemistry, because biocatalysts are compatible with and can be adjusted to many reaction conditions, as well as substrates. Their integration in multicomponent reactions (MCRs) allows for sim...

  • Article
  • Open Access
1 Citations
6,089 Views
9 Pages

A Novel Multi-Component Reaction to Imidazo[4,5-g]-quinazolines

  • Li Li,
  • Qianqian Zhang,
  • Bo Liu and
  • Gang Liu

16 May 2013

The trace impurities discovered after extended storage of a 5-amino- benzimidazole library were determined as imidazo[4,5-g]quinazoline derivatives by extensive spectroscopic data analysis. The formation of this highly aromatic heterocyclic ring invo...

  • Review
  • Open Access
204 Citations
19,469 Views
71 Pages

Synthesis of Biologically Active Molecules through Multicomponent Reactions

  • Daniel Insuasty,
  • Juan Castillo,
  • Diana Becerra,
  • Hugo Rojas and
  • Rodrigo Abonia

24 January 2020

Focusing on the literature progress since 2002, the present review explores the highly significant role that multicomponent reactions (MCRs) have played as a very important tool for expedite synthesis of a vast number of organic molecules, but also,...

  • Article
  • Open Access
42 Citations
9,896 Views
28 Pages

Droplet-Assisted Microfluidic Fabrication and Characterization of Multifunctional Polysaccharide Microgels Formed by Multicomponent Reactions

  • Nicolas Hauck,
  • Nalin Seixas,
  • Silvia P. Centeno,
  • Raimund Schlüßler,
  • Gheorghe Cojoc,
  • Paul Müller,
  • Jochen Guck,
  • Dominik Wöll,
  • Ludger A. Wessjohann and
  • Julian Thiele

21 September 2018

Polysaccharide-based microgels have broad applications in multi-parametric cell cultures, cell-free biotechnology, and drug delivery. Multicomponent reactions like the Passerini three-component and the Ugi four-component reaction are shown in here to...

  • Article
  • Open Access
7 Citations
2,817 Views
18 Pages

Greener Synthesis of Antiproliferative Furoxans via Multicomponent Reactions

  • Mariana Ingold,
  • Victoria de la Sovera,
  • Rosina Dapueto,
  • Paola Hernández,
  • Williams Porcal and
  • Gloria V. López

Prostate and bladder cancers are commonly diagnosed malignancies in men. Several nitric oxide donor compounds with strong antitumor activity have been reported. Thus, continuing with our efforts to explore the chemical space around bioactive furoxan...

  • Review
  • Open Access
34 Citations
6,554 Views
23 Pages

Gold Catalyzed Multicomponent Reactions beyond A3 Coupling

  • Renso Visbal,
  • Sara Graus,
  • Raquel P. Herrera and
  • M. Concepción Gimeno

4 September 2018

The preparation of complex architectures has inspired the search for new methods and new processes in organic synthesis. Multicomponent reactions have become an interesting approach to achieve such molecular diversity and complexity. This review inte...

  • Article
  • Open Access
19 Citations
5,855 Views
10 Pages

8 November 2013

A series of 2-arylquinazolines have been synthesized in moderate to excellent yields by one-pot tandem reaction of (2-aminophenyl)methanols, aldehydes and ceric ammonium nitrate (CAN). The utility of this transformation was demonstrated by its compat...

  • Review
  • Open Access
37 Citations
7,451 Views
19 Pages

A Concise Review of Multicomponent Reactions Using Novel Heterogeneous Catalysts under Microwave Irradiation

  • Thirupathi Damera,
  • Ramakanth Pagadala,
  • Surjyakanta Rana and
  • Sreekantha Babu Jonnalagadda

24 June 2023

Multi-component reactions for the construction of heterocycles have been fascinated by microwave energy as an alternative technique of heating, owing to the advantages over traditional reflux methods. The heterogeneous catalysts contribute significan...

  • Review
  • Open Access
30 Citations
4,033 Views
24 Pages

The direct C–H multifunctionalization of quinoxalin-2(1H)-ones via multicomponent reactions has attracted considerable interest due to their diverse biological activities and chemical profile. This review will focus on recent achievements. It m...

  • Proceeding Paper
  • Open Access
1,421 Views
7 Pages

13 November 2021

Low molecular weight gelators, LMWGs, are small molecules that can self-associate in organic solvents or in water to form fibrous supramolecular architectures and three-dimensional networks that present important applications in several fields. Altho...

  • Review
  • Open Access
34 Citations
8,652 Views
23 Pages

Stereoselective Multicomponent Reactions in the Synthesis or Transformations of Epoxides and Aziridines

  • Allan Ribeiro da Silva,
  • Deborah Araujo dos Santos,
  • Marcio Weber Paixão and
  • Arlene Gonçalves Corrêa

11 February 2019

Small ring heterocycles, such as epoxides and aziridines, are present in several natural products and are also highly versatile building blocks, frequently involved in the synthesis of numerous bioactive products and pharmaceuticals. Because of the p...

  • Review
  • Open Access
11 Citations
3,534 Views
25 Pages

7 September 2023

Multicomponent reactions (MCRs) have undoubtedly emerged as the most indispensable tool for organic chemists worldwide, finding extensive utility in the synthesis of intricate natural products, heterocyclic molecules with significant bioactivity, and...

  • Feature Paper
  • Review
  • Open Access
28 Citations
5,773 Views
20 Pages

Green Catalysts and/or Green Solvents for Sustainable Multi-Component Reactions

  • Gatien Messire,
  • Emma Caillet and
  • Sabine Berteina-Raboin

4 September 2024

Here, we describe some well-known multicomponent reactions and the progress made over the past decade to make these processes even more environmentally friendly. We focus on the Mannich, Hantzsch, Biginelli, Ugi, Passerini, Petasis, and Groebke&ndash...

  • Article
  • Open Access
4 Citations
4,082 Views
13 Pages

16 December 2019

Tri- or tetrasubstituted furans have been prepared from terminal activated olefins and acyl chlorides or anhydrides by a multicomponental convergent synthesis mode. Instead of stoichiometric nBu3P, only catalytic nBu3P or nBu3P=O is needed to furnish...

  • Article
  • Open Access
1 Citations
1,003 Views
12 Pages

Decarboxylation-Driven Double Annulations: Innovative Multi-Component Reaction Pathways

  • Desheng Zhan,
  • Gang Yang,
  • Tieli Zhou,
  • Sashirekha Nallapati and
  • Xiaofeng Zhang

A concerted five-component reaction strategy has been developed, featuring double [3+2] cycloadditions utilizing aspartic acid. This approach provides valuable insights into mechanistic pathways, allowing for the distinction between concerted and ste...

  • Proceeding Paper
  • Open Access
1 Citations
1,711 Views
6 Pages

Ultrasound-Assisted Ugi-Azide Multicomponent Reaction for the Synthesis of 1,5-Disubstituted Tetrazoles

  • Alejandro Corona-Díaz,
  • Sandra C. Ramírez-López,
  • David Calderón-Rangel,
  • Cristian Saldaña-Arredondo and
  • Rocío Gámez-Montaño

15 November 2023

The Ugi-azide MCR (UA) is one of the most efficient methods for the synthesis of 1,5-disubstituted-1H-tetrazoles (1,5-DS-T). Complex drug-like scaffolds incorporating tetrazoles have demonstrated a wide range of therapeutic benefits such as anti-infl...

  • Article
  • Open Access
47 Citations
11,972 Views
8 Pages

Sulfated Zirconia-Catalyzed Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones (DHPMs) Under Solventless Conditions: Competitive Multicomponent Biginelli vs. Hantzsch Reactions

  • Deyanira Angeles-Beltrán,
  • Leticia Lomas-Romero,
  • Victor H. Lara-Corona,
  • Eduardo González-Zamora and
  • Guillermo Negrón-Silva

2 October 2006

The catalytic ability of ZrO2/SO42- to promote solventless three-componentcondensation reactions of a diversity of aromatic aldehydes, urea or thoiurea and ethylacetoacetate was studied. Products resulting from Hantzsch and/or Biginelli multi-compone...

  • Review
  • Open Access
5 Citations
2,197 Views
12 Pages

Recent Progress on Multi-Component Reactions Involving Nucleophile, Arynes and CO2

  • Shaoxuan Gong,
  • Xiumei Xie,
  • Hongxia Sun,
  • Yuting Liu,
  • Junjie Li and
  • Zhen Zhang

Carbon dioxide (CO2) is a non-toxic, abundant and recoverable source of carbon monoxide. Despite its thermodynamically stable and kinetically inert nature, research on CO2 utilisation is ongoing. CO2-based aryne reactions, crucial for synthesising or...

  • Review
  • Open Access
4 Citations
2,689 Views
39 Pages

Magnetic Nanoparticle-Catalysed One-Pot Multicomponent Reactions (MCRs): A Green Chemistry Approach

  • Venkatesan Kasi,
  • Magdi EI Sayed Abdelsalam Zaki,
  • Hussain Basha Nabisahebgari,
  • Hussain Shaik,
  • Sook-Keng Chang,
  • Ling Shing Wong,
  • Karthikeyan Parasuraman and
  • Sobhi Mohamed Gomha

22 August 2025

The synthesis of heterocyclic compounds has gained significant attention in organic chemistry due to their diverse pharmacological properties. However, traditional synthetic approaches often involve hazardous chemicals, high energy consumption, and t...

  • Article
  • Open Access
7 Citations
7,141 Views
13 Pages

Asymmetric Synthesis of 1,3-Oxazolidine Derivatives with Multi-Component Reaction and Research of Kinetic Resolution

  • Xiao-Wei Hong,
  • Yu-Qiang Zhou,
  • Cui-Bing Bai,
  • Nai-Xing Wang,
  • Yalan Xing,
  • Wei Zhang,
  • Yan-Jing Wang,
  • Xing-Wang Lan,
  • Yu Xie and
  • Yi-He Li

18 September 2015

An efficient multi-component reaction to synthesize multi-substituted 1,3-oxazolidine compounds of high optical purity was described. All the products were well-characterized and the absolute configuration of one chiral center was determined. The pla...

  • Review
  • Open Access
89 Citations
11,727 Views
28 Pages

27 December 2021

In this review, we comprehensively describe catalyzed multicomponent reactions (MCRs) and the multiple roles of catalysis combined with key parameters to perform these transformations. Besides improving yields and shortening reaction times, catalysis...

  • Article
  • Open Access
4 Citations
5,212 Views
23 Pages

Multicomponent Domino Reaction in the Asymmetric Synthesis of Cyclopentan[c]pyran Core of Iridoid Natural Products

  • Alejandro Manchado,
  • Victoria Elena Ramos,
  • David Díez and
  • Narciso M. Garrido

13 March 2020

The asymmetric synthesis of a compound with the cyclopentan[c]pyran core of iridoid natural products in four steps and 40% overall yield is reported. Our methodology includes a one-pot tandem domino reaction which provides a trisubstituted cyclopenta...

  • Article
  • Open Access
2,352 Views
17 Pages

Multicomponent Reactions Promoted by Ecocatalyst from Metal Hyperaccumulating Plant Pluchea sagittalis

  • Leonardo H. R. Alponti,
  • Monize Picinini,
  • Ernesto A. Urquieta-Gonzalez,
  • Caroline S. da Silva,
  • Simone Y. S. Silva,
  • Sebastião C. Silva,
  • Marilene N. de Oliveira,
  • Juliana Viera,
  • Maria Fatima das G. F. da Silva and
  • Arlene G. Corrêa

7 October 2023

Phytoremediation has been considered a sustainable environmental technology for heavy metals decontamination. In this work, we evaluated the metal contents by inductively coupled plasma optical emission spectrometry (ICP-OES) of three plant species c...

  • Article
  • Open Access
4 Citations
4,457 Views
14 Pages

Efficient AntiMycolata Agents by Increasing the Lipophilicity of Known Antibiotics through Multicomponent Reactions

  • Angela Trejo,
  • Carme Masdeu,
  • Irene Serrano-Pérez,
  • Marina Pedrola,
  • Narcís Juanola,
  • Ouldouz Ghashghaei,
  • Guadalupe Jiménez-Galisteo,
  • Rodolfo Lavilla,
  • Francisco Palacios and
  • Miguel Viñas
  • + 1 author

New antibiotic agents were prepared using Povarov and Ugi multicomponent reactions upon the known drugs sulfadoxine and dapsone. The prepared derivatives, with increased lipophilicity, showed improved efficiency against Mycolata bacteria. Microbiolog...

  • Feature Paper
  • Article
  • Open Access
11 Citations
4,077 Views
13 Pages

8 February 2021

We report here the use of eucalyptol as a bio-based solvent for Hiyama coupling, cyanation, and multicomponent reactions on O,S,N-heterocycles. These heterocycles were chosen as targets or as starting materials given their biological potential; they...

  • Review
  • Open Access
18 Citations
4,548 Views
18 Pages

Heterocycle-Based Multicomponent Reactions in Drug Discovery: From Hit Finding to Rational Design

  • Pau Nadal Rodríguez,
  • Ouldouz Ghashghaei,
  • Andrea Bagán,
  • Carmen Escolano and
  • Rodolfo Lavilla

In the context of the structural complexity necessary for a molecule to selectively display a therapeutical action and the requirements for suitable pharmacokinetics, a robust synthetic approach is essential. Typically, thousands of relatively simila...

  • Review
  • Open Access
5 Citations
3,385 Views
59 Pages

13 September 2025

Quinazolin-4(3H)-ones are nitrogen heterocycles that have attracted considerable interest over many years due to their important biological and pharmacological properties. It has been shown that quinazolinone derivatives exhibit, e.g., analgesic, ant...

  • Feature Paper
  • Article
  • Open Access
1 Citations
1,530 Views
12 Pages

Efficient Synthesis of Tetrasubstituted Furans via Lipase-Catalyzed One-Pot Sequential Multicomponent Reaction

  • Yongqi Zeng,
  • Yong Tang,
  • Minglu Xu,
  • Dantong Wang,
  • Zhi Wang,
  • Yin Gao and
  • Lei Wang

15 May 2025

Tetrasubstituted furans and their derivatives represent a versatile class of important heterocyclic frameworks widely distributed in natural products. These scaffolds also demonstrate significant potential in pharmaceutical chemistry, materials scien...

  • Communication
  • Open Access
1 Citations
2,568 Views
11 Pages

1 February 2023

Catalyst-free multicomponent reactions of mixed alkylzinc reagents with Michael acceptors and aldehydes, ketones or activated imines are described. Primary, secondary and tertiary alkylzinc reagents, pre-generated in acetonitrile from the correspondi...

  • Proceeding Paper
  • Open Access
1,550 Views
6 Pages

Semisynthesis of 6β-Acetoxyvouacapane Derivatives via the Ugi-Azide Multicomponent Reaction

  • Gabriela Servín-García,
  • Luis Chacón-García,
  • Joaquín González-Marrero,
  • Mariana Macías-Alonso,
  • Mario A. Gómez-Hurtado,
  • Gabriela Rodríguez-García,
  • Rosa E. del Río and
  • Carlos J. Cortés-García

14 November 2022

A semisynthesis of 6β-acetoxyvouacapane-1,5-disusbtituted tetrazoles derivatives from the leaves of Caesalpinia platyloba by using the Ugi-azide multicomponent reaction as a key step reaction is described. To our knowledge, this is the first rep...

  • Article
  • Open Access
2 Citations
1,067 Views
17 Pages

29 October 2024

Supercritical multicomponent thermal fluid technology is a new technology with obvious advantages in offshore heavy oil recovery. However, there is currently insufficient understanding of the generation characteristics of the supercritical multicompo...

  • Article
  • Open Access
10 Citations
3,556 Views
15 Pages

Antioxidant Activity of Bioactive Peptide Fractions from Germinated Soybeans Conjugated to Fe3O4 Nanoparticles by the Ugi Multicomponent Reaction

  • Yarelys Elena Augusto-Jimenez,
  • Marcela González-Montoya,
  • Dany Naranjo-Feliciano,
  • Daniel Uribe-Ramírez,
  • Eliseo Cristiani-Urbina,
  • Carlos Díaz-Águila,
  • Hernani Yee-Madeira and
  • Rosalva Mora-Escobedo

22 September 2021

The conjugation of biomolecules to magnetic nanoparticles has emerged as promising approach in biomedicine as the treatment of several diseases, such as cancer. In this study, conjugation of bioactive peptide fractions from germinated soybeans to mag...

  • Article
  • Open Access
18 Citations
4,470 Views
18 Pages

Access to New Cytotoxic Triterpene and Steroidal Acid-TEMPO Conjugates by Ugi Multicomponent-Reactions

  • Haider N. Sultani,
  • Ibrahim Morgan,
  • Hidayat Hussain,
  • Andreas H. Roos,
  • Haleh H. Haeri,
  • Goran N. Kaluđerović,
  • Dariush Hinderberger and
  • Bernhard Westermann

Multicomponent reactions, especially the Ugi-four component reaction (U-4CR), provide powerful protocols to efficiently access compounds having potent biological and pharmacological effects. Thus, a diverse library of betulinic acid (BA), fusidic aci...

  • Article
  • Open Access
2 Citations
3,954 Views
10 Pages

Structure-Acid Lability Relationship of N-alkylated α,α-dialkylglycine Obtained via a Ugi Multicomponent Reaction

  • Iván Ramos-Tomillero,
  • Marisa K. Sánchez,
  • Hortensia Rodríguez and
  • Fernando Albericio

2 January 2021

Using the classical Ugi four-component reaction to fuse an amine, ketone, carboxylic acid, and isocyanide, here we prepared a short library of N-alkylated α,α-dialkylglycine derivatives. Due to the polyfunctionality of the dipeptidic scaf...

  • Review
  • Open Access
7 Citations
3,393 Views
18 Pages

4 November 2022

We discuss herein the problems associated with using melting points to characterize multicomponent reactions’ (MCRs) products and intermediates. Although surprising, it is not rare to find articles in which these MCRs final adducts (or their in...

  • Article
  • Open Access
2 Citations
4,382 Views
27 Pages

28 December 2021

Steroid sapogenin diosgenin is of significant interest due to its biological activity and synthetic application. A consecutive one-pot reaction of diosgenin, oxalyl chloride, arylacetylenes, and phenylhydrazine give rise to steroidal 1,3,5-trisubstit...

  • Article
  • Open Access
15 Citations
4,866 Views
15 Pages

Green Synthesis of Spiro Compounds with Potential Anticancer Activity through Knoevenagel/Michael/Cyclization Multicomponent Domino Reactions Organocatalyzed by Ionic Liquid and Microwave-Assisted

  • Regina Westphal,
  • Eclair Venturini Filho,
  • Laiza Bruzadelle Loureiro,
  • Cláudio Francisco Tormena,
  • Claudia Pessoa,
  • Celina de Jesus Guimarães,
  • Mariana Palmeira Manso,
  • Rodolfo Goetze Fiorot,
  • Vinicius Rangel Campos and
  • Sandro José Greco
  • + 2 authors

19 November 2022

In this work a microwave-assisted Knoevenagel/Michael/cyclization multicomponent domino methodology, using ethanol as solvent and the ionic liquid 1-methylimidazolium chloride as catalyst was developed for the synthesis of spiro compounds. The reacti...

  • Article
  • Open Access
4 Citations
3,780 Views
18 Pages

3 July 2019

For the numerical simulation of convection-dominated reacting flow problems governed by convection-reaction equations, grids-based Eulerian methods may cause different degrees of either numerical dissipation or unphysical oscillations. In this paper,...

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