Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• a 73% yield. The Suzuki coupling of boronate 6a and aryl bromide 9a using palladium acetate and cesium carbonate in the presence of the ligand SPhos [25] yielded biaryl 10a with virtually quantitative yield (98%, Scheme 4). Unfortunately, the removal of non-identified byproducts and of 9a (which had

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• binding properties [25] and reactions with bovine serum albumin [27]. Cyclam is known as a tetraamino-macrocyclic ligand, which binds strongly to give complexes with many transition metal cations. While catalytic applications of square planar cyclam complexes are reported for metals, such as Ni [30][31

• showed no interaction with Au(III), as expected. A similar resistance to coordinate was observed for the open diamides 1c–e. The phosphorus containing ligand 1c did undergo phosphorus oxidation instead of Au(III) coordination. No effect was obtained by refluxing or by adding additives, such as silver

• ) coordination [43][45][46], Likewise, Δδ1Hcoord 0.3–0.5 ppm for all the neighboring N–CH and N–CH2 protons indicated ligand tetra-coordination to Au(III), as well. Upon coordination of ligand 5a, four different 15N NMR values for the nitrogens were observed. This might be explained by the nitrogens becoming non

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• considers the interaction at multiple binding sites, which might be identical or non-identical. Thus, the model is generally applicable for any possible scenario with more than one ligand. In addition to the enthalpy, the titration curve contains direct information of the stoichiometries and equilibrium

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• . Finally, we turned out attention to transition metal-catalyzed formation of phenols from aryl halides [5]. After another round of screening, we successfully applied palladium-catalyzed conditions discovered by the Buchwald group [6], using KOH as the nucleophile and X-Phos as the ligand, to afford 7 in 83

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• that the catalyst efficiency is almost constant even after five cycles, but the rate of the reaction considerably decreased from the first cycle (0.31 min−1) to the fifth cycle (0.15 min−1). Zhang, Lu, et al. prepared β-CD-decorated CdS nanocrystals (CdS–CD, Figure 9) via a ligand-exchange reaction

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• ] promotes the binding of ligands exhibiting a high local negative charge density, such as sulfotyrosinated P-selectin glycoprotein ligand-1 (PSGL-1) [23] or heparin [24]. A versatile synthetic ligand that takes advantage of binding to cationic target sites, is dendritic polyglycerol sulfate [25] (dPGS), due

• achieved. As specific biological interactions strongly rely on the receptor–ligand interplays, we are interested in investigating the targeting of isolated receptors by supramolecular polymers built from peptide amphiphiles decorated with suitable ligand structures. The well-known L-selectin described

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• nature, but not less important. They possess biological properties, such as nicotinic acetylcholine receptor (nAChR) ligand [10][11], CNS (central nervous system) activity [12][13], and chemical defense [14][15][16]. Structurally, homotropane alkaloids have different skeletons including [3.3.1], [4.2.1

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• protein–ligand interactions and conformational changes within a protein complex. In addition to this, HDXMS has the advantage of using a low concentration of proteins (in the high-nM or low-µM range) and providing higher-resolution data on the solvent accessibility, compared to probes used in protein

• Kd, can be calculated [36]. Another commonly used biophysical method is ITC. In ITC, the binding partner is mixed with the protein solution at various concentrations, and the heat released or absorbed as the proteins (or the protein and the ligand) interact is measured. Since the measurements are

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• minima. Ph3P was chosen as the ligand in analogy to the previous calculations on compound 1 [16]. Computational discussion In analogy to similar processes [11][21][22][40][41], the reaction is initiated by a two-step [3,3]-acetate rearrangement [42], triggered by the coordination of the cationic gold

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• ] cycloadditions, which are usually under substrate-control. Remarkable innovation of the stereoselective palladium-catalyzed trimethylenemethane cycloaddition reported by Trost’s group, which makes use of catalytic amounts of palladium and chiral phosphine ligand 74, was applied successfully in the

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• heparin stabilizes the tetrameric structure, without its tryptase dissociates into inactive monomers. The reported cationic ligand binds at the rim of anionic residues around the entrance of the central pore, blocks the access to the active sites, and inhibits enzyme activity. Schmuck et al. reported a

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

• Tim Holtum,
• Vikas Kumar,
• Daniel Sebena,
• Jens Voskuhl and
• Sebastian Schlücker

Beilstein J. Org. Chem. 2020, 16, 2911–2919, doi:10.3762/bjoc.16.240

• selectivity for monitoring the CBS, but the resulting UVRR spectrum overlaps with the UV-excited autofluorescence from the aromatic binding partners. This necessitates the use of a laser excitation <260 nm for spectrally separating the UVRR spectrum of the supramolecular ligand from the UV-excited

• autofluorescence of the peptide or protein. Here, we demonstrate the use of UVRR spectroscopy with 244 nm laser excitation for the characterization of GCP as well as guanidiniocarbonyl indole (GCI), a next generation supramolecular ligand for the recognition of carboxylates. For demonstrating the feasibility of

• strengths. Various spectroscopic techniques can be employed for monitoring these changes. For example, electronic absorption or fluorescence spectroscopy can probe the spectral differences due to the complexation of the supramolecular ligand with a peptide or protein. However, electronic spectroscopies

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• undemanding building blocks. The plethora of self-sorting systems depends on either the geometric fit of their global shapes and/or matching of their local interactions. Various noncovalent interactions, such as H‐bonding [8][9], metal–ligand coordination [10][11][12][13], electrostatic interactions [14], π

• hand denotes the formation of a single entity from all constituents using orthogonal binding motifs. In the self-sorting of more than two components, thus at least one ligand has to be multivalent (Figure 2). Clearly, heteromeric self-sorting has a superior value for switching because it allows for

• -interlocked catenanes. When both cages were mixed without C70, the dynamic combinatorial library (DCL) of seven compositionally distinct mixed-ligand Zn4L6 cages was observed (Figure 5b). An efficient self-sorting was only observed after the addition of the guest C70. As expected, the cage [Zn4(8')6]8

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• ICD bands, which are mostly pronounced with a linker length of n = 4 (with a2) and n = 5 (with 22AG), thus indicating that each ligand–G4-DNA complex has a specific structure with respect to relative alignment and conformational flexibility of the ligand in the binding site. It was shown exemplarily

• with one representative ligand from the series that such berberine–adenine conjugates exhibit a selective binding, specifically a selectivity to quadruplex DNA in competition with duplex DNA, and a preferential thermal stabilization of the G4-DNA forms 22AG and KRAS. Notably, the experimental data do

• several human cancer cells, but has only a relatively low cytotoxicity in healthy cells [31][32]. Berberine is also known as a G4-DNA ligand [33]. Especially berberine derivatives that carry additional substituents with varying alkyl chain lengths in the 9- and 13-position show enhanced binding properties

A heterobimetallic tetrahedron from a linear platinum(II)-bis(acetylide) metalloligand

• Matthias Hardy,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2020, 16, 2701–2708, doi:10.3762/bjoc.16.220

• Matthias Hardy Marianne Engeser Arne Lutzen University of Bonn, Kekulé-Institute of Organic Chemistry and Biochemistry, Gerhard-Domagk-Str. 1, D-53121 Bonn, Germany 10.3762/bjoc.16.220 Abstract Employing 4-ethynylaniline as a simple organic ligand we were able to prepare the stable trans-bis

• these two design concepts – the subcomponent self-assembly strategy and the complex-as-a-ligand approach – ensured a fast and easy synthesis of large heterobimetallic coordination cages of tetrahedral shape with a diameter of more than 3 nm as a mixture of all three possible T-, S4- and C3-symmetric

• ligand syntheses is the subcomponent self-assembly strategy [18][19][20][21][22][23]. Following this strategy, the actual ligand is generated in situ during the self-assembly process via reversible formation of covalent bonds, in most cases imine bonds. Despite this achievement, addressing even higher

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• immobilized zinc(II)–dipicolylamine groups increased. A nanoparticle containing a 9:1 ratio of the solubilizing and the anion-binding ligand showed a color change at diphosphate and triphosphate concentrations as low as 10 μmol/L, for example, and precipitated at slightly higher concentrations

• unfunctionalized ligand furthermore mediates the nanoparticle solubility, preferentially in an aqueous environment that is often most suited for practical applications. Since we wondered whether this concept could be extended to receptor types other than cyclopeptides, we sought for recognition motifs that also

• receptors based on other scaffolds [22][23][24][25]. To test whether this binding motif induces AuNP crosslinking, we synthesized nanoparticles containing peripheral zinc(II)–DPA complexes together with a solubilizing triethylene glycol-based ligand in different ratios and studied their interaction with

Selective and reversible 1,3-dipolar cycloaddition of 6-aryl-1,5-diazabicyclo[3.1.0]hexanes with 1,3-diphenylprop-2-en-1-ones under microwave irradiation

• Alexander P. Molchanov,
• Mariia M. Efremova,
• Mariya A. Kryukova and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2020, 16, 2679–2686, doi:10.3762/bjoc.16.218

• earlier that the electronic properties of the substituted aryl group of diaziridines and chalcones showed a profound influence on the yields of a catalytic reaction (scandium triflate with a chiral ligand); when a phenyl or p-chloro/methylphenyl-substituted diaziridine was employed, the cycloaddition

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• geometry of 2 might be favoured in AChE but not in BACE-1. These possibilities all remain speculative in the absence of high-resolution structural data of the enzyme–ligand complexes. Conclusion A threo-difluorinated piperine analog (2) was successfully synthesised through a stepwise route. The

A consensus-based and readable extension of Linear Code for Reaction Rules (LiCoRR)

• Benjamin P. Kellman,
• Yujie Zhang,
• Emma Logomasini,
• Eric Meinhardt,
• Karla P. Godinez-Macias,
• Austin W. T. Chiang,
• James T. Sorrentino,
• Chenguang Liang,
• Bokan Bao,
• Yusen Zhou,
• Sachiko Akase,
• Isami Sogabe,
• Thukaa Kouka,
• Elizabeth A. Winzeler,
• Iain B. H. Wilson,
• Matthew P. Campbell,
• Sriram Neelamegham,
• Frederick J. Krambeck,
• Kiyoko F. Aoki-Kinoshita and
• Nathan E. Lewis

Beilstein J. Org. Chem. 2020, 16, 2645–2662, doi:10.3762/bjoc.16.215

• three types of uncertainty operators. The ligand “ ... ”, the continuation “ _ ”, and the branch “ | ”. Each has a specific syntactic match, but intuitively, the ligand is a chain that can contain branches, the continuation is a chain that can include branches terminated outside of the continuation, and

•  1). More specifically, (1) the ligand uncertainty operator indicates a chain of MSs that can include attached branches completely contained in the substring, (2) the continuation uncertainty operator indicates a chain of MSs that can include attached branches that may not be wholly contained in the

• substring, and (3) the possible branch uncertainty operator indicates where a branch may be included in the substring. Due to the nuances of representing a glycan linearly, these are not complete definitions. Ligand “…” – A ligand is a fragment of a larger molecule connected to the rest of the molecule at

Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches

• Jannis Ludwig,
• Tobias Moje,
• Fynn Röhricht and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210

• ], switchable NMR relaxation agents [8][9][10], and building blocks for molecular spintroncis [11]. Our modular design is based on three components: a) a Ni(II)-porphyrin (square planar base complex), b) an azoaryl unit (photoswitchable ligand) and c) a molecular linker or tether (connecting the porphyrin with

• the switchable ligand). This approach has been dubbed “record player” design for obvious reasons (Figure 1a). The Ni-porphyrin (“disk”) is low-spin if the azo-aryl unit (“tone arm”) is in trans configuration. Upon switching to the bent cis configuration, the lone pair of the pyridine (or imidazole

• substituents at the pyridine or imidazole part) to increase the Ni–ligand coordination strength. Strong coordination in turn improves the performance of the spin switch, namely the conversion rate to the cis isomer, the conversion rate to the high-spin state, as well as the thermal stability of the high-spin

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• analysis of the extensive structural data can be overwhelming. Rapid analysis of trajectory data, with tools available in the Galaxy platform, can be used to understand key features and compare differences that inform the preferential ligand structure that favors binding. We illustrate this informatics

• analysis were carried out. These analyses were used to rapidly assess key features of the system, interrogate the dynamic structure of the ligand, and determine the role of glycosylation on the conformational equilibrium. The glycopeptide conformations in solution change relative to the peptide; thus a

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• modulate protein–protein interactions. Here we present NMR methods that have been applied to characterize these molecular interactions and discuss the challenges of this endeavor. Keywords: molecular recognition; NMR; protein ligand interaction; protein surfaces; supramolecular chemistry; Introduction In

• been used to design custom plugs for the negatively charged central cavity of tetrameric proteins, exploiting the four-fold symmetry of the ligand [39][40]. In the case of tetrameric voltage-dependent potassium channels, binding of the calixarene to the central pore of the channel results in reversible

• Survivin – Histone H3 interaction by a GCP ligand has been shown to inhibit tumor proliferation in cell culture [46]. Porphyrins, either with or without a complexed metal ion in the center, have been used as planar hydrophobic scaffolds where either negatively charged carboxylate or positively charged

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• utilities for virtual glycosylation, protein–glyco-ligand docking, and glycan “loop” modelling. This tool is best for the researcher with basic knowledge and skills to work with a command-line interface (Linux). PolysGlycanBuilder. PolysGlycanBuilder [76] is a web-based tool (http://glycan

Catalytic trifluoromethylation of iodoarenes by use of 2-trifluoromethylated benzimidazoline as trifluoromethylating reagent

• Tatsuhiro Uchikura,
• Nanami Kamiyama,
• Taisuke Ishikawa and
• Takahiko Akiyama

Beilstein J. Org. Chem. 2020, 16, 2442–2447, doi:10.3762/bjoc.16.198

• -trifluoromethylbenzimidazoline derivative as the trifluoromethylating reagent and a catalytic amount of Cu(I) in the presence of 2,2'-bipyridyl as the ligand. Through a mechanistic study, we found that the oxidative addition of the iodoarene to the Cu(I)–CF3 species is the rate-determining step. Keywords: benzimidazoline

• , trifluoromethylacetophenone and phenylenediamine derivatives (Figure 1b). Herein we report a catalytic trifluoromethylation of iodoarenes by use of benzimidazoline derivatives in the presence of a catalytic amount of copper salts and a bipyridyl ligand (Figure 1c). Results and Discussion We first investigated the reaction

• yield of 3a even at a high temperature (Table 1, entries 2 and 3). In order to stabilize the copper(I) catalyst, a bipyridyl ligand was employed in the reaction [23]. By this, the trifluoromethylation proceeded with a catalytic amount of CuI in the presence of 0.8 equiv of 2,2’-bipyridyl to furnish

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• gadolinium catalyst and chiral ligand L2 (Scheme 43b) [108]. By altering the radical precursor to α-silyl amines 277 and using α,β-unsaturated amides 278, Yoon et al. found that the reactions could be stopped at the RCA step to give enantioenriched 1,4-addition products 279 using a scandium catalyst and

• chiral ligand L3 (Scheme 44a) [109]. The putative mechanism proceeds via a reductive quenching cycle to give nucleophilic α-amino radicals 277•, which can add to the β-position of Lewis acid complex 280 to give the α-carbonyl radical 280•. Instead of a cyclisation, this radical is then reduced by the

• transition metal Lewis acids 291a–e that can coordinate to ketone substrates and form chiral photoactive complexes 292, which in many cases act as the in situ generated photocatalyst (Scheme 48) [115]. They have recently developed an example using an indazole-based ligand [116] to add to their well