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New Approach in Multicomponent Reactions

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Organic Chemistry".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 25385

Special Issue Editors

Department of Organic and Inorganic Chemistry, Universidad de Extremadura, Badajoz, Spain
Interests: organic chemistry; synthetic organic chemistry; multicomponent reactions; heterocyclic chemistry; green chemistry; materials chemistry; bioorganic chemistry
Special Issues, Collections and Topics in MDPI journals
Department of Organic and Inorganic Chemistry, Universidad de Extremadura, Badajoz, Spain
Interests: synthetic methodology; multicomponent reactions; heterocyclic chemistry; bioactive molecules
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Multicomponent reactions are highly convergent processes that permit the synthesis of complex molecules in a simple procedure. This synthetic methodology has been widely used in different research fields, such as medicinal chemistry, combinatorial chemistry, green chemistry, or materials chemistry. Particularly, multicomponent reactions are outstandingly suited for diversity diversity-oriented chemistry, constituting an excellent tool in order to explore the chemical molecular space. Multicomponent chemistry is now more active than ever, and new approaches are being developed every day to give response to the challenges of contemporary organic chemistry.

You may choose our Joint Special Issue in Chemistry.

Dr. Ana Maria Gomez Neo
Dr. Carlos M. Fernández Marcos
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Multicomponent reaction
  • MCR
  • New synthetic methodologies
  • Isocyanides
  • Green chemistry
  • Diversity-oriented chemistry

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Published Papers (10 papers)

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Research

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15 pages, 12264 KiB  
Article
Protection-Free Strategy for the Synthesis of Boro-Depsipeptides in Aqueous Media under Microwave-Assisted Conditions
by Shuo-Bei Qiu, Pei-Yao Liu, Bo-Cheng Wang, Pin-Rui Chen, Jing-Han Xiao, Ting-Yu Hsu, Kuan-Lin Pan, Zhi-Yin Lai, Yi-Wei Chen, Ying-Chuan Chen, Jen-Kun Chen and Po-Shen Pan
Molecules 2022, 27(7), 2325; https://doi.org/10.3390/molecules27072325 - 04 Apr 2022
Viewed by 1727
Abstract
In this report, 19 boron-containing depsipeptides were synthesized via microwave-assisted Passerini three-component reaction (P-3CR) in an aqueous environment. The linker-free DAHMI fluorescent tagging approach was used on selected boron-containing compounds to study the relationship between their structures and their level of cellular uptake [...] Read more.
In this report, 19 boron-containing depsipeptides were synthesized via microwave-assisted Passerini three-component reaction (P-3CR) in an aqueous environment. The linker-free DAHMI fluorescent tagging approach was used on selected boron-containing compounds to study the relationship between their structures and their level of cellular uptake of HEK293 cells. The biological data retrieved from the DAHMI experiments indicated that while the structures of tested compounds may be highly similar, their bio-distribution profile could be vastly distinctive. The reported optimized one-pot synthetic strategy along the linker-free in vitro testing protocol could provide an efficient platform to accelerate the development of boron-containing drugs. Full article
(This article belongs to the Special Issue New Approach in Multicomponent Reactions)
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13 pages, 14484 KiB  
Article
Influence of Steric Effect on the Pseudo-Multicomponent Synthesis of N-Aroylmethyl-4-Arylimidazoles
by Nerith Rocio Elejalde-Cadena, Mayra García-Olave, David Figueroa, Pietro Vidossich, Gian Pietro Miscione and Jaime Portilla
Molecules 2022, 27(4), 1165; https://doi.org/10.3390/molecules27041165 - 09 Feb 2022
Cited by 2 | Viewed by 1456
Abstract
A pseudo-three-component synthesis of N-aroylmethylimidazoles 3 with three new C–N bonds formed regioselectively under microwave conditions was developed. Products were obtained by reacting two equivalents of aroylmethyl bromide (ArCOCH2Br, 1) with the appropriate amidine salt (RCN2H3 [...] Read more.
A pseudo-three-component synthesis of N-aroylmethylimidazoles 3 with three new C–N bonds formed regioselectively under microwave conditions was developed. Products were obtained by reacting two equivalents of aroylmethyl bromide (ArCOCH2Br, 1) with the appropriate amidine salt (RCN2H3.HX, 2) and with K2CO3 as a base in acetonitrile. The bicomponent reaction also occurred, giving the expected 4(5)-aryl-1H-imidazoles 4. Notably, the ratio of products 3 and 4 is governed by steric factors of the amidine 2 (i.e., R = H, CH3, Ph). Therefore, a computational study was carried out to understand the reaction course regarding product ratio (3/4), regioselectivity, and the steric effects of the amidine substituent group. Full article
(This article belongs to the Special Issue New Approach in Multicomponent Reactions)
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13 pages, 2274 KiB  
Article
Photoinitiated Multicomponent Anti-Markovnikov Alkoxylation over Graphene Oxide
by Liang Nie, Xiangjun Peng, Haiping He, Jian Hu, Zhiyang Yao, Linyi Zhou, Ming Yang, Fan Li, Qing Huang and Liangxian Liu
Molecules 2022, 27(2), 475; https://doi.org/10.3390/molecules27020475 - 12 Jan 2022
Cited by 1 | Viewed by 1473
Abstract
The development of graphene oxide–based heterogeneous materials with an economical and environmentally–friendly manner has the potential to facilitate many important organic transformations but proves to have few relevant reported reactions. Herein, we explore the synergistic role of catalytic systems driven by graphene oxide [...] Read more.
The development of graphene oxide–based heterogeneous materials with an economical and environmentally–friendly manner has the potential to facilitate many important organic transformations but proves to have few relevant reported reactions. Herein, we explore the synergistic role of catalytic systems driven by graphene oxide and visible light that form nucleophilic alkoxyl radical intermediates, which enable an anti-Markovnikov addition exclusively to the terminal alkenes, and then the produced benzyl radicals are subsequently added with N–methylquinoxalones. This photoinduced cascade radical difunctionalization of olefins offers a concise and applicable protocol for constructing alkoxyl–substituted N–methylquinoxalones. Full article
(This article belongs to the Special Issue New Approach in Multicomponent Reactions)
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14 pages, 2259 KiB  
Article
A One-Pot Six-Component Reaction for the Synthesis of 1,5-Disubstituted Tetrazol-1,2,3-Triazole Hybrids and Their Cytotoxic Activity against the MCF-7 Cell Line
by Cesia M. Aguilar-Morales, Jorge Gustavo Araujo-Huitrado, Yamilé López-Hernández, Claudia Contreras-Celedón, Alejandro Islas-Jácome, Angelica Judith Granados-López, Cesar R. Solorio-Alvarado, Jesús Adrián López, Luis Chacón-García and Carlos J. Cortés-García
Molecules 2021, 26(20), 6104; https://doi.org/10.3390/molecules26206104 - 10 Oct 2021
Cited by 8 | Viewed by 2170
Abstract
A high-order multicomponent reaction involving a six-component reaction to obtain the novel linked 1,5-disubstituted tetrazole-1,2,3-triazole hybrids in low to moderate yield is described. This one-pot reaction is carried out under a cascade process consisting of three sequential reactions: Ugi-azide, bimolecular nucleophilic substitution (S [...] Read more.
A high-order multicomponent reaction involving a six-component reaction to obtain the novel linked 1,5-disubstituted tetrazole-1,2,3-triazole hybrids in low to moderate yield is described. This one-pot reaction is carried out under a cascade process consisting of three sequential reactions: Ugi-azide, bimolecular nucleophilic substitution (SN2), and copper-catalyzed alkyne–azide reaction (CuAAC), with high atom and step-economy due the formation of six new bonds (one C-C, four C-N, and one N-N). Thus, the protocol developed offers operational simplicity, mild reaction conditions, and structural diversity. Finally, to evaluate the antitumoral potential of the synthetized molecules, a proliferation study was performed in the breast cancer (BC) derived cell line MCF-7. The hybrid compounds showed several degrees of cell proliferation inhibition with a remarkable effect in those compounds with cyclohexane and halogens in their structures. These compounds represent potential drug candidates for breast cancer treatment. However, additionally assays are needed to elucidate their complete effect over the cellular hallmarks of cancer. Full article
(This article belongs to the Special Issue New Approach in Multicomponent Reactions)
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13 pages, 6663 KiB  
Article
Three-Component Suzuki–Knoevenagel Synthesis of Merocyanine Libraries and Correlation Analyses of Their Oxidation Potentials and Optical Band Gaps
by Tim Meyer, Roxanne Krug and Thomas J. J. Müller
Molecules 2021, 26(17), 5149; https://doi.org/10.3390/molecules26175149 - 25 Aug 2021
Cited by 8 | Viewed by 1767
Abstract
The Suzuki coupling Knoevenagel condensation one-pot synthesis of boronic acids/esters, (hetero)aromatic bromo aldehydes and methylene active compounds is a highly practical consecutive three-component process to provide substance libraries with 60 donor-π-bridge-acceptor molecules, i.e., merocyanines in a broader sense, in moderate to excellent yield. [...] Read more.
The Suzuki coupling Knoevenagel condensation one-pot synthesis of boronic acids/esters, (hetero)aromatic bromo aldehydes and methylene active compounds is a highly practical consecutive three-component process to provide substance libraries with 60 donor-π-bridge-acceptor molecules, i.e., merocyanines in a broader sense, in moderate to excellent yield. As already seen with the naked eye, a broad variation of the optical properties becomes accessible using this practical synthetic tool. More systematically, correlation analyses upon plotting the optical band gaps against the first oxidation potentials of redox active systems of consanguineous series furnishes linear correlations and, by extension, two parameter plots (oxidation potential and emission maximum) planar correlations with the optical band gaps. Full article
(This article belongs to the Special Issue New Approach in Multicomponent Reactions)
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12 pages, 1178 KiB  
Article
Cyanovinylation of Aldehydes: Organocatalytic Multicomponent Synthesis of Conjugated Cyanomethyl Vinyl Ethers
by Samuel Delgado-Hernández, Fernando García-Tellado and David Tejedor
Molecules 2021, 26(14), 4120; https://doi.org/10.3390/molecules26144120 - 06 Jul 2021
Cited by 3 | Viewed by 2373
Abstract
A novel organocatalytic multicomponent cyanovinylation of aldehydes was designed for the synthesis of conjugated cyanomethyl vinyl ethers. The reaction was implemented for the synthesis of a 3-substituted 3-(cyanomethoxy)acrylates, using aldehydes as substrates, acetone cyanohydrin as the cyanide anion source, and methyl propiolate as [...] Read more.
A novel organocatalytic multicomponent cyanovinylation of aldehydes was designed for the synthesis of conjugated cyanomethyl vinyl ethers. The reaction was implemented for the synthesis of a 3-substituted 3-(cyanomethoxy)acrylates, using aldehydes as substrates, acetone cyanohydrin as the cyanide anion source, and methyl propiolate as the source of the vinyl component. The multicomponent reaction is catalyzed by N-methyl morpholine (2.5 mol%) to deliver the 3-(cyanomethoxy)acrylates in excellent yields and with preponderance of the E-isomer. The multicomponent reaction manifold is highly tolerant to the structure and composition of the aldehyde (aliphatic, aromatic, heteroaromatics), and it is instrumentally simple (one batch, open atmospheres), economic (2.5 mol% catalyst, stoichiometric reagents), environmentally friendly (no toxic waste), and sustainable (easy scalability). Full article
(This article belongs to the Special Issue New Approach in Multicomponent Reactions)
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19 pages, 1591 KiB  
Communication
Ugi Reaction on α-Phosphorated Ketimines for the Synthesis of Tetrasubstituted α-Aminophosphonates and Their Applications as Antiproliferative Agents
by Adrián López-Francés, Xabier del Corte, Edorta Martínez de Marigorta, Francisco Palacios and Javier Vicario
Molecules 2021, 26(6), 1654; https://doi.org/10.3390/molecules26061654 - 16 Mar 2021
Cited by 9 | Viewed by 2185
Abstract
An Ugi three-component reaction using preformed α-phosphorated N-tosyl ketimines with different isocyanides in the presence of a carboxylic acid affords tetrasubstituted α-aminophosphonates. Due to the high steric hindrance, the expected acylated amines undergo a spontaneous elimination of the acyl group. The reaction [...] Read more.
An Ugi three-component reaction using preformed α-phosphorated N-tosyl ketimines with different isocyanides in the presence of a carboxylic acid affords tetrasubstituted α-aminophosphonates. Due to the high steric hindrance, the expected acylated amines undergo a spontaneous elimination of the acyl group. The reaction is applicable to α-aryl ketimines bearing a number of substituents and several isocyanides. In addition, the densely substituted α-aminophosphonate substrates showed in vitro cytotoxicity, inhibiting the growth of carcinoma human tumor cell line A549 (carcinomic human alveolar basal epithelial cell). Full article
(This article belongs to the Special Issue New Approach in Multicomponent Reactions)
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18 pages, 2680 KiB  
Article
Synthesis of Chromeno[3,4-b]piperazines by an Enol-Ugi/Reduction/Cyclization Sequence
by Ana Bornadiego, Ana G. Neo and Carlos F. Marcos
Molecules 2021, 26(5), 1287; https://doi.org/10.3390/molecules26051287 - 27 Feb 2021
Cited by 3 | Viewed by 1921
Abstract
Keto piperazines and aminocoumarins are privileged building blocks for the construction of geometrically constrained peptides and therefore valuable structures in drug discovery. Combining these two heterocycles provides unique rigid polycyclic peptidomimetics with drug-like properties including many points of diversity that could be modulated [...] Read more.
Keto piperazines and aminocoumarins are privileged building blocks for the construction of geometrically constrained peptides and therefore valuable structures in drug discovery. Combining these two heterocycles provides unique rigid polycyclic peptidomimetics with drug-like properties including many points of diversity that could be modulated to interact with different biological receptors. This work describes an efficient multicomponent approach to condensed chromenopiperazines based on the novel enol-Ugi reaction. Importantly, this strategy involves the first reported post-condensation transformation of an enol-Ugi adduct. Full article
(This article belongs to the Special Issue New Approach in Multicomponent Reactions)
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14 pages, 4247 KiB  
Article
Keto-Enol Tautomerism in Passerini and Ugi Adducts
by Pablo Pertejo, Andrea Sancho-Medina, Tomás Hermosilla, Beatriz González-Saiz, Javier Gómez-Ayuso, Roberto Quesada, Daniel Moreno, Israel Carreira-Barral and María García-Valverde
Molecules 2021, 26(4), 919; https://doi.org/10.3390/molecules26040919 - 09 Feb 2021
Cited by 7 | Viewed by 2904
Abstract
The use of arylglyoxal as starting material in Passerini and Ugi reactions affords β-ketoamides. This has allowed to study keto-enol tautomerism in these systems and assess the way in which the presence of acyloxy or aminoacyl groups bound to the C2 position affects [...] Read more.
The use of arylglyoxal as starting material in Passerini and Ugi reactions affords β-ketoamides. This has allowed to study keto-enol tautomerism in these systems and assess the way in which the presence of acyloxy or aminoacyl groups bound to the C2 position affects such tautomerism, and to investigate the reactivity of both the enol and carbonyl forms. In this work we also prove the versatility of the Passerini reaction, since depending on the conditions to which the corresponding adducts are subjected different products of synthetic interest can be obtained. Full article
(This article belongs to the Special Issue New Approach in Multicomponent Reactions)
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Review

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23 pages, 2607 KiB  
Review
Petasis vs. Strecker Amino Acid Synthesis: Convergence, Divergence and Opportunities in Organic Synthesis
by Wayiza Masamba
Molecules 2021, 26(6), 1707; https://doi.org/10.3390/molecules26061707 - 18 Mar 2021
Cited by 16 | Viewed by 5124
Abstract
α-Amino acids find widespread applications in various areas of life and physical sciences. Their syntheses are carried out by a multitude of protocols, of which Petasis and Strecker reactions have emerged as the most straightforward and most widely used. Both reactions are three-component [...] Read more.
α-Amino acids find widespread applications in various areas of life and physical sciences. Their syntheses are carried out by a multitude of protocols, of which Petasis and Strecker reactions have emerged as the most straightforward and most widely used. Both reactions are three-component reactions using the same starting materials, except the nucleophilic species. The differences and similarities between these two important reactions are highlighted in this review. Full article
(This article belongs to the Special Issue New Approach in Multicomponent Reactions)
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