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Search for "Ugi" in Full Text gives 78 result(s) in Beilstein Journal of Organic Chemistry.
Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis
Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118
- Abstract The multicomponent synthesis of prolyl pseudo-peptide catalysts using the Ugi reaction with furfurylamines or isocyanides is described. The incorporation of such a polymerizable furan handle enabled the subsequent polymerization of the peptide catalyst with furfuryl alcohol, thus rendering
- 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
- synthesis of prolyl pseudo-peptides having a furan ring handle, which could be subsequently incorporated into PFA during the polymerization process. Results and Discussion To this end, a solution-phase multicomponent procedure based on the Ugi four-component reaction (Ugi-4CR) [14], was employed to
Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams
Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104
- and heteroaromatic amines 2 and trimethylsilyl enol ethers 39 are combined in a three-component Mannich/lactamization reaction in the presence of an indium catalyst to yield twenty four 3-difluoroalkylisoindolinone derivatives 40. The starting 2-formylbenzoic acid 33 has been also employed in Ugi-type
- equivalents of 2-formylbenzoic acid (33) in an Ugi three-component reaction with methanol as solvent at room temperature to afford tetrahydrodiisoindoloquinoxalinecarboxamides 43 (Scheme 12). More recently, Shafiee et al. [90] utilized propargylamine as the cycle-nitrogen delivering component and then
- analogues of these compounds by a sequential Ugi/Diels–Alder approach and, in this context, they were able to separate the enantiomers using chiral chromatography. Some of these compounds showed good in vitro potency blocking the cardiac ion channel Kv1.5 and, therefore, are promising agents to treat atrial
Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions
Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88
- macroheterocycles in a reduced number of steps. Keywords: consecutive/repetitive multicomponent reactions; isocyanide; isocyanide-based multicomponent reactions; (macro)heterocycles; Passerini reaction; Ugi reaction; Introduction Isocyanide (isonitrile) chemistry was first described by Lieke in 1859 [1] and forms
- the basis of a large group of reactions in organic chemistry, especially in isocyanide-based multicomponent reactions (IMCRs) [2][3], such as the Passerini and Ugi reactions, which are reactions that have been widely used in the synthesis of peptides, peptidomimetics and heterocycles [4][5][6][7][8
- , which is able to undergo both electrophilic and nucleophilic reactions at the carbon atom. The Ugi reaction, firstly reported by Ugi et al. in 1959 [14], involves an amine, a ketone or aldehyde, an isocyanide, and a carboxylic acid to form a dipeptide product. It is undoubtedly one of the most important
Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides
Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82
- synthesis of a novel category of pseudo-peptides via intramolecular Ugi reaction of levulinic acid (4-oxopentanoic acid), aromatic and aliphatic amines, and amino acid-based isocyanides is reported. Levulinic acid was applied as a bifunctional substrate containing both carbonyl and acid moieties suitable
- for the Ugi reaction. This article provides a facile and convenient one-pot procedure for the synthesis of peptide-like heterocyclic molecules containing 2-pyrrolidone (γ-lactam), amide and ester functional groups with good to excellent yields. Keywords: amino acid-based isocyanides; levulinic acid
- ; multicomponent; pseudo-peptides; Ugi reaction; Introduction The multistep synthesis of complex molecules normally requires a large number of repetitive synthetic operations, such as extraction, separation, chromatography and other purification steps. These disadvantages encouraged chemists to synthesize complex
Selectivity in multiple multicomponent reactions: types and synthetic applications
Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46
- early example involves the synthesis of protease inhibitors by double Ugi 4CR using pyridine-2,6-dicarboxylic acid, isocyanides, amines and aldehydes (Scheme 2), and the combinatorial implications of this protocol were analyzed [6]. Ugi and Dömling soon realized the potential of such experiments, which
- connected through long linear alkyl chains. Representative examples include polymerizations using Biginelli [12], Passerini [13], Ugi [14], metal-catalyzed MCRs [15], and reactive combinations involving an alkyne-sulfonyl azide nucleophile [16] and sulfur, amines and isocyanides [17] (Scheme 3). An
- aromatic and aliphatic substrates to peptides, steroids, sugars, etc.) [26], but also from the different MCRs used. Although the Ugi 4CR is the most commonly used transformation in this context, interesting examples exploiting other MCRs have been reported (Scheme 6) [27][28]. However, when the first MCR
Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists
Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45
- synthesis was accomplished by a rapid, one-pot synthesis of indole-based macrocycles based on Ugi macrocyclization. The reaction of 12 different α,ω-amino acids and different indole-3-carboxaldehyde derivatives afforded a unique library of macrocycles otherwise difficult to access. Screening of the library
- for p53-MDM2 inhibition by fluorescence polarization and 1H,15N HSQC NMR measurements confirm MDM2 binding. Keywords: 1H,15N HSQC NMR; indole; macrocycles; multicomponent; p53-MDM2; Ugi reaction; Introduction Macrocycles are the chemical entities that are consisting of a 12-membered or even bigger
- ]. Herein, an indole-based macrocycle synthesis is reported in a one-pot fashion based on Ugi macrocyclization with readily available α,ω-amino acids. Moreover, in continuation of our efforts in the design and synthesis of macrocycles targeting the p53–MDM2 interaction demonstrating the potential of these
Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells
Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11
- triple-negative breast cancer MDA-MB-468 cells. Keywords: drug targeting; neuropeptide Y; PDC; peptide–drug conjugate; targeted tumor therapy; tubugi; tubulysin A; Ugi reaction; Introduction Until recently, the medication of tumor diseases was primarily based on more or less unspecific
- three cell lines was determined as proof for targeted delivery. Results and Discussion Synthesis of tubugi-1 building blocks We established the Ugi reaction as a powerful tool for peptide synthesis and ligation, including the first syntheses of tubulysine derivatives by us and later also others [44][53
- ][55][56]. In a single step, the Ugi reaction permits the introduction of different functionalities which may be followed with additional modifications on the side chain (e.g., via ring-closing metathesis or Click reaction) [53]. For tubugi conjugates we learned that alkyl amide bonds and several types
Unprecedented nucleophile-promoted 1,7-S or Se shift reactions under Pummerer reaction conditions of 4-alkenyl-3-sulfinylmethylpyrroles
Beilstein J. Org. Chem. 2018, 14, 2722–2729, doi:10.3762/bjoc.14.250
- rearrangement of 6,7-dihydroindol-4(5H)-ones. However, after implementing this approach, an undesirable isomer was obtained [21]. Although a number of acid- [22][23] and metal-catalysed cascade processes [24][25] have been developed (for example, Pictet–Spengler [26] and Ugi-type reactions [27], the acyl
Gold-catalyzed post-Ugi alkyne hydroarylation for the synthesis of 2-quinolones
Beilstein J. Org. Chem. 2018, 14, 2572–2579, doi:10.3762/bjoc.14.234
- University, 53 Kabanbay Batyr Ave, Block 7, Astana, 010000, Republic of Kazakhstan 10.3762/bjoc.14.234 Abstract A series of propargylamides containing an electron-rich benzene ring was prepared through the Ugi reaction of 3,5-dimethoxyaniline with various propiolic acids, aldehydes and isocyanides
- . Subjecting these adducts to a gold-catalyzed intramolecular alkyne hydroarylation process allowed to efficiently construct the 2-quinolone core bearing a branched substituent on the nitrogen atom. Keywords: gold catalysis; hydroarylation; 2-quinolones; Ugi reaction; Introduction Quinoline and its oxidized
- address this issue by employing propargylamides 7 obtained by a four-component Ugi reaction of propiolic acids 3, aldehydes 4, isocyanides 5 and 3,5-dimethoxyaniline (6a) (Scheme 2). We anticipated that the resulting adducts 7 would readily produce 2-quinolones 8 bearing a branched substituent on the
Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry
Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179
- an organophotocatalytic version of the Ugi reaction. These procedures were undertaken in a flow chemistry set-up, using irradiation by green LEDs and Rose Bengal as the photocatalyst (Scheme 13) [56]. The scope of the reaction is fairly broad, especially considering the method was developed in a flow
- and their core structural characteristics are quite drug like. The products of the Ugi-type reaction the group report are also interesting. The functional group (FG) compatibility of the reaction is very good, as many of the FGs tolerated can be further functionalised in a plethora of different ways
Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence
Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74
- spiro[indoline-3,2'-pyrrolidine]-2,5'-diones, via a post-Ugi-domino transamidation/cyclization sequential process, has been achieved in three sequential steps utilizing a one-pot reaction protocol. The variation in carboxylic acid substrates allows for the generation of new chiral racemic quaternary
- carbon centers under basic conditions providing molecular diversity and a small library of spirocyclic oxindoles. Keywords: convertible isocyanides; lactams; molecular diversity; oxindoles; transamidation; Introduction The Ugi-multicomponent coupling reaction [1][2], followed by post-modification
- transformations involving tandem reaction sequences [3] and the Ugi–deprotection–cyclization (UDC) strategies [4][5][6][7][8] have been exploited as powerful tools allowing access to biological and pharmaceutical high-value heterocyclic scaffolds [9][10][11]. These reactions are appealing in that they are atom
Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins
Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49
- (CSIR-NIIST), Thiruvananthapuram-19, India 10.3762/bjoc.14.49 Abstract A practical three-step protocol for the assembly of triazolobenzodiazepine-fused diketopiperazines and hydantoins has been developed. The synthesis of these tetracyclic ring systems was initiated by an Ugi reaction, which brought
- together all necessary functionalities for further transformations. The Ugi adducts were then subjected to a base-induced ring closing and an intramolecular azide–alkyne cycloaddition reaction in succession to obtain highly fused benzodiazepine frameworks. Keywords: benzodiazepine; 2,5-diketopiperazine
- ; hydantoin; intramolecular azide–alkyne cycloaddition; Ugi reaction; Introduction The versatile bioactivities of multiring-fused heterocyclic scaffolds continue to attract significant attention in developing new methods for their synthesis. A plethora of functionalized fused heterocycles can be easily
Consecutive hydrazino-Ugi-azide reactions: synthesis of acylhydrazines bearing 1,5-disubstituted tetrazoles
Beilstein J. Org. Chem. 2017, 13, 2596–2602, doi:10.3762/bjoc.13.256
- bearing 1,5-disubstituted tetrazoles. Our strategy was accomplished in only three steps: first, a one-pot hydrazino-Ugi-azide four-component reaction; second a hydrazinolysis and finally an additional hydrazino-Ugi-azide reaction. This sequence provides the title compounds in moderate to excellent yields
- . The products synthesized herein contain functional groups within their structures that can be easily modified to obtain new acylhydrazino 1,5-disubstituted tetrazoles. Keywords: acylhydrazines; consecutive Ugi reactions; 1,5-disubstituted tetrazoles; isocyanide-based multicomponent reactions (IMCRs
- ); Ugi-azide reaction; Introduction Tetrazoles are extensively studied, useful non-natural heterocyclic skeletons with the highest nitrogen content among the stable heterocycles [1][2]. The tetrazole-ring system has a variety of applications in organic chemistry, coordination chemistry, and agriculture
Mechanochemical synthesis of small organic molecules
Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186
- 2016 Juaristi and co-workers have reported Ugi 4-component reactions (4-CR) by liquid-assisted grinding (LAG) using MeOH. Equimolar amounts of benzaldehyde, chloroacetic acid, tert-butyl isocyanide, and propargylamine in the presence of 2 mol % InCl3, under ball-mill yielded the desired Ugi product in
- reaction of electron-rich arenes [88][98]. Mechanochemical aryl halogenation reaction using trihaloisocyanuric acids [100]. Mechanochemical fluorination reaction by LAG method [102]. Mechanochemical Ugi reaction [116]. Mechanochemical Passerine reaction [116]. Mechanochemical synthesis of α-aminonitriles
Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid
Beilstein J. Org. Chem. 2017, 13, 1478–1485, doi:10.3762/bjoc.13.146
- prehalogenation [16]. iii) The multicomponent method: only two strategies have been reported to the best of our knowledge. One is a combination of the Ugi reaction, which uses 2,4-dimethoxybenzylamine, arylglyoxal, carboxylic acid, and isonitrile as components, and a subsequent Robinson–Gabriel reaction [17]. The
A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline
Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138
- non-classical inputs for the Joullié–Ugi reaction and for subsequent preparation [28] of sterically encumbered, constrained peptidomimetic frameworks. Diversely substituted indolenines 9 are easy to prepare via the Fischer indole synthesis [26] and their use in the CCR can be expected to result in
New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized
Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104
- amine component in Ugi and Groebke–Blackburn–Bienaymé multicomponent reactions. The first example of an application of aminoazoles in an Ugi four-component reaction was discovered and novel features of a Groebke–Blackburn–Bienaymé cyclocondensation are established and discussed. The heterocycles
- -aryl-1H-pyrazole-4-carboxamides; antibacterial activity; Groebke–Blackburn–Bienaymé reaction; isocyanide Ugi reaction; Introduction An intensive progress in pharmaceutical and medicinal chemistry, as well as in the generation and improvement of medicinal technologies has led to defeating a wide scope
- -based MCRs as the Ugi four-component reaction (Ugi-4CR) and the Groebke–Blackburn–Bienaymé reaction (GBB-3CR) in combination with post-cyclizations are powerful tools to access diversity as well as complexity in a one-pot procedure; in this way they largely cover the available chemical space [9][10][11
A practical and efficient approach to imidazo[1,2-a]pyridine-fused isoquinolines through the post-GBB transformation strategy
Beilstein J. Org. Chem. 2017, 13, 817–824, doi:10.3762/bjoc.13.82
- conditions and a broad substrate scope, allowing for the rapid construction of structurally complex and diverse heterocycles in moderate to good yields. Keywords: Groebke–Blackburn–Bienaymé reaction; imidazo[1,2-a]pyridines; isoquinolines; multicomponent reaction; Ugi reaction; Introduction Imidazo[1,2-a
- discovery [22][23][24][25][26][27]. The Ugi reaction [28], an elegant pioneer of a multicomponent reaction, represents a powerful synthetic tool to assemble versatile peptide-like compounds. It has found many applications in the facile synthesis of natural products and biologically interesting molecules [29
- ][30]. Although the Ugi-4CR generates linear α-acylamino-amides, a wide range of heterocycles are accessible through the combination with other transformations (post-transformation strategy) [31]. For example, the Ugi/Diels–Alder process leads to the formation of benzofurans and indoles [32] as well as
Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif
Beilstein J. Org. Chem. 2017, 13, 728–733, doi:10.3762/bjoc.13.72
- -tetrafluorocyclohexane aldehydes 4 were used successfully in Ugi multicomponent reactions [11][12]. In this paper we report the preparation of amines of this series starting from a Birch reduction on benzonitrile, and with a similar methyl iodide quench, to generate amines 5, which are stable to hydrogen fluoride
Brønsted acid-mediated cyclization–dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines
Beilstein J. Org. Chem. 2017, 13, 428–440, doi:10.3762/bjoc.13.46
- for the synthesis of many alkaloids (Figure 1) [16]. To synthesize pyrazinoisoquinoline and its derivatives, various approaches such as the Ugi multicomponent reaction [17] amidoalkylation [18][19], N-acyliminium ion cyclization [20] and a radical cyclization [21] have been reported. To this end
- . 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
Synthesis of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones via sequential Biginelli and Passerini reactions
Beilstein J. Org. Chem. 2017, 13, 54–62, doi:10.3762/bjoc.13.7
- dihydropyridine synthesis (1882), the Biginelli dihydropyrimidone synthesis (1891), the Mannich reaction (1912), the Passerini three-component reaction (1921) and the Ugi four-component reaction (1959) [9]. In this work, we used Biginelli and Passerini reactions to synthesize highly functionalized compounds
- ][27]. So far, only a few examples of multicomponent tandem reactions are described in the literature [28][29]. Portlock et al. reported on Petasis–Ugi tandem reactions leading to a product with six different side chains [30][31]. Al-Tel et al. combined the Groebke–Blackburn reaction with either
- Passerini or Ugi reactions in a sequential one-pot procedure [32]. Furthermore, up to eight components were reacted by the combination of three multicomponent reactions [33]. In 2010, the Ugi reaction and the Ugi–Smiles reaction were combined by Westermann et al. [34]. In addition, the Ugi reaction was used
Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions
Beilstein J. Org. Chem. 2016, 12, 2865–2872, doi:10.3762/bjoc.12.285
- for the synthesis of acylhydrazino-peptomers, a new class of peptidomimetics. The key idea in this approach is based on a simple route using a one-pot hydrazino-Ugi four-component reaction followed by a hydrazinolysis or hydrolysis reaction and subsequent hydrazino-Ugi reaction or classical Ugi
- peptidomimetics with potential biological activity. Keywords: acylhydrazino-peptomers; consecutive Ugi reactions; peptide-peptoid hybrid; peptomer; Introduction In the last decades, increasing efforts have been extensively carried out to improve the pharmacological properties of natural peptides by structural
- difficult sequences [48]. It is therefore important to have alternative methods for the fast and easy construction of such important compounds. In this sense, the Ugi four-component reaction (U-4CR) has proven to be a robust and versatile method for the synthesis of peptoids and peptide-peptoid hybrids
Catalytic Wittig and aza-Wittig reactions
Beilstein J. Org. Chem. 2016, 12, 2577–2587, doi:10.3762/bjoc.12.253
- that afforded isocyanates 52. These were in turn treated in situ with catalyst 44 to afford the final products 50 via presumed iminophosphorane intermediates 53. Subsequently this research group used a very similar strategy for the synthesis of polysubstituted benzimidazoles 54 via sequential Ugi and
Application of heterocyclic aldehydes as components in Ugi–Smiles couplings
Beilstein J. Org. Chem. 2016, 12, 2032–2037, doi:10.3762/bjoc.12.191
- Katelynn M. Mason Michael S. Meyers Abbie M. Fox Sarah B. Luesse Department of Chemistry, Southern Illinois University Edwardsville, Edwardsville, Illinois 62026, USA 10.3762/bjoc.12.191 Abstract Efficient one-pot Ugi–Smiles couplings are reported for the use of furyl-substituted aldehyde
- components. In the presence of these heterocyclic aldehydes, reactions tolerated variations in amine components and led to either isolated N-arylamide Ugi–Smiles adducts or N-arylepoxyisoindolines, products of tandem Ugi–Smiles Diels–Alder cyclizations, in moderate yields. A thienyl-substituted aldehyde was
- also a competent component for Ugi–Smiles adduct formation. Keywords: Diels–Alder cycloaddition; epoxyisoindoline; multicomponent coupling reaction; tandem reaction; Ugi–Smiles coupling; Introduction Synthetic methods to efficiently prepare libraries of biologically-relevant compounds are in demand
One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction
Beilstein J. Org. Chem. 2016, 12, 1487–1492, doi:10.3762/bjoc.12.145
- scaffolds can be constructed in great diversity by a multicomponent reaction of amidines, aldehydes and isocyanides. This MCR, a variant of the Ugi reaction [24][25], was discovered independently by three groups and is known as the Groebke–Blackburn–Bienaymé (GBB) reaction [26][27][28][29]. The reaction
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