The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• urgent need to find novel, effective and safe drugs for cancer therapy. Recently, focusing on the design of more potent anticancer drug candidates using more sustainable synthetic processes, we report a new Ugi four-component reaction approach for easy access to Ugi-derived isatin-peptoids in moderate to

• processes, a second family of α-acetamide carboxamide oxindole derivatives 5 was obtained using the previously optimized Ugi4CR approach [16] (Scheme 2 and Figure 2). Taking into account the preliminary SAR studies reported for the first family of Ugi-derived isatin-peptoids, the second family was obtained

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• solid state by X-ray crystallography (dimer 2), and implicit solvent QM geometry optimizations. N-(Methylamino)peptoids were found to preferentially adopt trans amide bonds with the side chain N–H bonds oriented approximately perpendicular to the amide plane. This orientation is conducive to local

• backbone stabilization through intra-residue hydrogen bonds but also to intermolecular associations. The high capacity of N-(methylamino)peptoids to establish intermolecular hydrogen bonds was notably deduced from pronounced concentration-dependent N–H chemical shift variation in 1H NMR and the

• antiparallel arrangement of mirror image molecules held together via two hydrogen bonds in the crystal lattice of dimer 2. Keywords: cis/trans isomerism; peptoid; structure; trans-inducing side chain; Introduction The term “peptoids” refers to the family of artificial oligo(poly)mers consisting of N

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• the first example in which the Ugi reactions were used in the construction and cyclization of peptoids in a combined fashion. The methodology was based on two consecutive four-component Ugi reactions for the construction of the acyclic precursors 84 and 89, followed by a final intramolecular Ugi

Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2016, 12, 2865–2872, doi:10.3762/bjoc.12.285

• some of the most important classes of peptidomimetics so far obtained and highlights the differences among them. Of these, peptoids (oligomers of N-substituted glycine residues) [9][10][11][12] are the most common and may have interesting biological activities. For instance, peptoid 1 is a target for

• cancer therapeutics for being an antagonist of the vascular endothelial growth factor receptor 2 [13]; peptoid 2 is a ligand of the protooncogene Crk [14]; and peptoids 3 and 4 showed a high affinity for the α1-adrenergic and μ-specific opiate receptors [15], respectively (Figure 2). Unlike peptides, in

• peptoids the side chain of the Cα is bound to the nitrogen atom. Due to the consequent lack of the polar N–H bonds, their lipophilicity is increased, which may result in improved membrane permeability [16][17]. Furthermore, peptoids have also found utility in supra- and macromolecular engineering [18] and

Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• Martin C. N. Brauer Ricardo A. W. Neves Filho Bernhard Westermann Ramona Heinke Ludger A. Wessjohann Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle/Saale, Germany 10.3762/bjoc.11.4 Abstract A library of ten 1,3-diyne-linked peptoids has been

• synthesized through an Ugi four-component reaction (U-4CR) followed by a copper-catalysed alkyne homocoupling (Glaser reaction). The short and chemoselective reaction sequence allows generating diverse (pseudo) dimeric peptoids. A combinatorial version allows the one-pot preparation of, e.g., six-compound

• -libraries of homo- and heterodimers verified by ESI-MS and HPLC. In a preliminary evaluation, some compounds display moderate activity against the Gram-positive bacterium Bacillus subtilis. Keywords: antibacterial; combinatorial; diynes; homodimerization; multicomponent reactions; peptoids; Ugi reaction

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• France, 103 Bd Saint-Michel, 75005 Paris, France 10.3762/bjoc.10.144 Abstract Cyclic N-propargyl α-peptoids of various sizes were prepared by way of macrocyclizations of linear N-substituted oligoglycines. These compounds were used as molecular platforms to synthesize a series of iminosugar clusters

• scaffold is crucial as it defines the valency, the size and the shape of the multivalent architectures. Due to their broad chemical diversity, rapid and convenient synthetic access, improved proteolytic stability and cell permeability over peptides, N-substituted glycine oligomers, called peptoids [14][15

• ][16][17], appear as promising scaffolds for the synthesis of glycoconjugates of biological interest [14][15][16][17][18]. Combination of these advantages has led to many examples of biologically active peptoids [19][20][21]. So far, some syntheses of N-, O-, C- and S-linked glycopeptoids have been

Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids

• Angélica de Fátima S. Barreto,
• Otilie E. Vercillo,
• Ludger A. Wessjohann and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2014, 10, 1017–1022, doi:10.3762/bjoc.10.101

• reactions; Passerini reaction; sansalvamide A; Ugi reaction; Introduction Peptoids are an interesting class of non-natural compounds that have recently received much attention due to their wide range of biological activities, which makes them attractive candidates for drug discovery [1][2][3][4][5][6][7

• in combinatorial synthesis [40][41][42][43] and can be used strategically for the synthesis of depsipeptoids. By analogy to peptides and peptoids, a depsipeptoid would be a peptoid bearing an ester group instead of an amide group. Differences between peptide, peptoid, depsipeptide and depsipeptoid

• structures are outlined in Figure 2. Results and Discussion In continuing our research on the synthesis of peptoids with potential pharmacological activity [12][17][18][44][45] and using a fast and efficient microwave-assisted synthesis of peptoids [15][17][18], we decided to carry out the synthesis of

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

Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

• Daniel Fürniss,
• Timo Mack,
• Frank Hahn,
• Sidonie B. L. Vollrath,
• Katarzyna Koroniak,
• Ute Schepers and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 56–63, doi:10.3762/bjoc.9.7

• fast methods for the decoration of biomimetic molecules with sugars is of fundamental importance. The glycosylation of peptoids and polyamines as examples of such biomimetic molecules is reported here. The method uses Cu-catalyzed azide alkyne cycloaddition to promote the reaction of azidosugars with

• either polyamines or peptoids. In addition, functionalized nucleic acids were attached to polyamines via the same route. Based on a modular solid-phase synthesis of peralkynylated peptoids with up to six alkyne groups, the latter were modified with azidosugar building blocks by using copper-catalyzed

• azide alkyne cycloadditions. In addition, the up-scaling of some particular azide-modified sugars is described. Keywords: click chemistry; glycans; peptoids; polyalkynes; polyamines; solid-phase chemistry; Introduction To date, oligosaccharides have gained more and more interest as potential drugs in

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

• peptoids as antibacterial agents [13][38][39][40][41][42][43][44][45][46][47], it was decided to investigate their activity against the Gram-negative bacterium Aliivibrio fischeri [48]. Compounds (−)-1 and (±)-1 were the most active ones with IC50 values of 45.0 ± 4.4 and 38.4 ± 5.8 μM, respectively. In

Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups

• H. Bauke Albada,
• Alina-Iulia Chiriac,
• Michaela Wenzel,
• Maya Penkova,
• Julia E. Bandow,
• Hans-Georg Sahl and
• Nils Metzler-Nolte

Beilstein J. Org. Chem. 2012, 8, 1753–1764, doi:10.3762/bjoc.8.200

• [14], trivalent lipidated short peptides with antifungal activity [15], peptoids [16], peptides containing D-amino acids [17], and foldamers based on β-amino acid residues with antibacterial activity [18] have been described. Whereas nature has to stick to products compatible with biosynthetic