Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• upon binding of the enolate molecule to iodine either through a carbon–iodine or an oxygen–iodine bond. Both intermediates, I and II, are in rapid equilibrium with each other and further undergo two different types of reactions: [1,2]-ligand coupling and [2,3]-rearrangement (Scheme 2). Either of these

Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide

• Parvathy Mini,
• Michael R. Grace,
• Genevieve H. Dennison and
• Kellie L. Tuck

Beilstein J. Org. Chem. 2024, 20, 2818–2826, doi:10.3762/bjoc.20.237

• , highly sensitive chemosensors via a facile synthetic route/method, we have explored three chelates for lanthanide ions (DO3A, 2,6-pyridinedicarboxylic acid and DO2A), resulting in complexes with different overall charges. Additionally we have explored two copper(II) binding groups (di(2-picolyl)amine and

• program, was used to determine the binding constant of Cu2+ ions to Tb.1 in both Tris-HCl buffer and HEPES buffer. The host–guest binding modes (1:1, 1:2 or 2:1) were evaluated using the luminescent data (λex = 250 nm, λem = 450–650 nm) from the respective titration experiments. In both cases the 1:1 host

• –guest binding model gave an acceptable fit with low (co)variance of the fit (Table 1). Aqueous buffer HS− studies of [Tb.1·3Cu]3+ The response of [Tb.1·3Cu]3+ to Na2S (HS− in solution at pH 7.4) in both 10 mM HEPES and 10 mM Tris-HCl was investigated. The addition of HS−(aq) ions to a solution of [Tb.1

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• this work was a preliminary evaluation of the potential bioactivity of the obtained compounds. In particular, a molecular docking experiment to investigate the binding mechanisms to the CYP51 enzyme and an evaluation of the antifungal activity of imidazo[1,2-a]pyrimidines against Candida albicans were

• desired pharmacological properties. Therefore, the design and synthesis of new compounds of this class with improved ADMET (absorption, distribution, metabolism, excretion, toxicity) pharmacological properties is an urgent task. Molecular docking was carried out to identify potential binding positions of

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• catalysts located at the top. The top of the volcano plot corresponds to the scenario where the catalyst exhibits high catalytic activity, as it achieves an optimal balance in binding to the reactants, neither too strongly nor too weakly (Figure 1A, purple points). The catalysts with binding energies lower

• File 1). Notably, the CO2 capture exhibits a lower activation barrier compared to the capture of epoxide (+10.0 kcal·mol−1 vs +30.0 kcal·mol−1). Using transition state theory [40] as expressed in Equation 1, the rate constants were calculated for binding to either molecule at 273.0 K, resulting in k1

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• substances. Host CDs are highly accommodative to water molecules as well and usually contain water in the native state. There is still an ongoing discussion on both the total number of water molecules and their preferred binding position inside the cavities of the CDs. To understand the hydration/dehydration

• (Figure 1B and C). Hydrated γ-CD Hydration and interaction with water (sequential binding of water molecules to the CD cavity) The γ-CD cavity was scanned for spots/sites with enhanced binding affinity for the incoming water molecules: γ-CD hydrates containing one to seven water molecules bound at various

•  3. The enthalpies estimated for the subsequent binding process of water molecules to γ-CD in both the gas phase (ΔH1) and aqueous medium (ΔH78) at both levels of theory are presented in Table 1. The two sets of calculations using different basis sets (M062X/6-31G(d,p) and M062X/6-311++G(d,p)//M062X

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• ][3][4][5][6][7]. What about other halogens? Pyran inter-halide analogues of carbohydrates were rarely investigated as new tools in glycobiology [8]. This is surprising since the incorporation of halogens can improve cellular uptakes and enhance membrane binding and permeation [9][10][11]. In addition

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• prototypic iodolium 1BArF with bromide (CCDC: 1145291) [5]. For the latter, such a dimeric binding motif was also found, with I–Br bond lengths of 3.1936(9) Å [83% of Σr] and 3.2299(9) Å [84% of Σr]. It can be concluded that stronger halogen bonding can be found in the crystal structure of iodoloisoxazolium

• 7Br, which hints that also in solution stronger binding to Lewis bases and therefore higher activity as catalyst may be expected (compared to prototypic iodolium 1Z). As a benchmark for the halogen-bonding strength in solution, the activation of (PPh3)AuCl was chosen. The activated gold(I) complex was

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• ; rearrangement; Introduction Nitrogen-containing organic compounds (sometimes referred to as alkaloids due to their basic properties) are of critical importance in medicinal chemistry because of their unique binding properties to biomolecules [1]. Out of 55 drug candidates, approved by the FDA in 2023, 28 (51

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• –azide (DTB–azide) linker still possesses strong binding to streptavidin (Kd ≈ 1 × 10−11 M), but it can be released by mild washing conditions with organic solvent and low pH (Figure 8C) [105][106]. Similarly, desthiobiotin releases upon HCD fragmentation a set of characteristic diagnostic ions including

• acid, base, or redox-labile parts of the linker [52]. Most recently, Wozniak et al. mapped the binding sites of a large small molecules library, which were equipped with a photo-crosslinker [110]. The study used the acid-cleavable dialkoxydiphenylsilane (DADPS) linker to release the probe–peptide

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• , signaling the binding of HFIP to 2c enhanced the electron transfer kinetics between the hypervalent iodine reagent and the electrode [45]. Further additions of HFIP further increased the current response and shifted the peak potential, with 10 µL and 15 µL of HFIP showing responses with Epr at −1.55 V and

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• the importance of DPMs in mind due to their utmost significance as a building block in the construction of porphyrinogens, related polypyrrolic macrocycles, and pigments [39][40][41]. As shown in Figure 1, these DPMs and many more have fruitfully been used by several research groups in sensing/binding

• outstanding optical properties [43]. Herein, we present for the first time three new mono-, di-, tri-dipyrromethane appended truxene derivatives with the intention to explore them for future sensing and/or binding properties. Results and Discussion To achieve our goal towards the construction of truxene

• prepared compounds. The anion sensing/binding studies of these DPMs in addition to their formylated derivatives is under progress in our laboratory and will be published in due course. As mention above truxene and its congeners have shown a plethora of uses in diverse fields. To our best knowledge, their

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• ]. An advantage of dendrimer-supported organocatalysts are their enzyme-like properties [111][112]. Selective binding and cooperative catalysis can give the catalyst high selectivity and activity. Interactions between the support and other components The interaction between the solid support and the

• binding with an electron-withdrawing group. This acidity can result in stronger hydrogen bonds between the substrate and the catalyst C30, which contains a bis(trifluoromethyl)phenyl-modified squaramide moiety. This stronger interaction potentially enhances the catalyst–substrate interaction, allowing for

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• –ligand complexes, and analyse MD outcomes. Moreover, selected case studies have been reported to highlight the importance of computational tools in studying protein–glycan systems, revealing the capability of these tools to provide valuable insights into the binding kinetics, energetics, and structural

• a wide array of glycan-binding proteins (GBP) [17], which have a unique capability to specifically interact with endogenous and/or exogenous glycans [18][19]. Thus, disclosing the molecular basis of protein–glycan interactions has a unique potential to help modulate a myriad of complex biological

• events affecting the health and well-being of living organisms and the natural environment. Being key participants in the molecular dialogue, glycan binding proteins emerge as fascinating and critical components of molecular events that regulate life at its core. Their functions span from the catalysis

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• the treatment of paroxysmal nocturnal hemoglobinuria, and CPI-637 (2), an inhibitor of both cyclic-AMP response element binding protein (CBP) and adenoviral E1A binding protein [14][15][16]. The N2-substituted indazole analogs pazopanib (3), an FDA-approved tyrosine kinase inhibitor used for the

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• possibility of different binding topologies to the α4β2 receptor. Betahistine (6) is an orally active 2-(2-aminoethyl)pyridine drug indicated for vestibular disorders like Meniere’s disease, whose patients exhibit acute vertigo attacks (Scheme 2) [11][12]. Gbahou et al. [13] demonstrated histaminergic synapse

• -hydroxytryptamine (a MAO-A substrate), in a molecular docking experiment tested against serotonin (Scheme 3). A similar class of benzofuran systems with attractive binding properties are those represented by 4-amino-3-(benzo[b]furan-2-yl)butanoic acids, baclofen analogs, elaborated to elucidate the structural

• from furanyl derivatives to thienyl-substituted compounds 17–23 in the search to elucidate structural features for accessing this receptor (Scheme 4). The chloride- and bromide-substituted thienyl derivatives encompassed micromolar to submicromolar activities in radioligand binding assays based on (R

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• diaryliodonium triflates such as 8 and 9 [13]. They studied a model reaction with 2-aminopyridine (1), p-tolualdehyde (10) and cyclohexyl isocyanide (11) both experimentally (by binding and kinetic studies) and theoretically (by density functional theory (DFT) calculations) (Scheme 5). Catalyst 8 was found to be

• binding constants, leading to higher equilibrium concentrations of the electrophilically activated substrates. The H-bonds also increased the electrostatic potential on the σ-hole of the I atom, resulting in higher charge transfer values from the ligated species. Although no comparison was made with

• template, selecting the ligand building blocks with highest affinity and bringing them in proximity within the binding site. Building blocks are opportunely chosen to have complementary reactivity and therefore to react irreversibly within the binding site and assemble into the final ligand. Before the

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• of a new chiral centre. Advances in understanding ligand–receptor interactions have facilitated the determination of optimal molecular conformations to enhance binding affinity, which can be achieved, in part, by introducing a spiro annelated ring to impart rigidity to the molecule. From a medicinal

• . Chromatographic purification was not required post-reaction. Some spiro products exhibited high binding affinity towards DNA, while others showed good cytotoxicity against different cancer cells (A545, MCF-7, HeLa, HL-60, SW480, HepG2, HT-29, and A549) with IC50 values within the micromolar range (2.18–18.54 µM

• synthesized compounds were evaluated for their DNA binding properties and screened for cytotoxicity against leukemia cancer cells (Jurkat), demonstrating IC50 values in the micromolar range (14.2 to 36.5 µM). Importantly, these derivatives exhibited minimal toxicity toward normal cells (PBMCs). Furthermore

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• fractionated cell cultures of M. alba with 49 was followed by irradiation with 365 nm light to generate reactive carbene from diazirine. This sequence allowed the formation of covalent bonds between the synthetic probe and binding proteins. The resulting mixture was subjected to a copper-catalyzed click

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• of RiPPs have a molecular weight between 1,000 and 5,000 Da. Peptide natural products exhibit high specificity and binding affinity to their corresponding targets [9][10]. The inhibition of protein–protein interactions is an emerging strategy in the development of novel therapeutics [11]. Binding to

• advance and are not recycled in the system. The amino acids are methylated either prior to tRNA binding or after. The efficiency of incorporating unnatural amino acids is lower, but Merryman and Green have demonstrated that an excess of tRNA can overcome this problem [47]. When attempting to incorporate

• biocatalytic applications. The co-crystallisation of LahSB with bound SAH provides important details about the structure–function relationship, the substrate–enzyme interaction, and the cofactor binding site (Figure 5). This structural information, including the residues involved in binding, is essential for

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• bridges, relatively short length of the surface loops, and the increased number of Pro and Arg residues [29]. A truncated β-agarase gene without the carbohydrate-binding modules (Aga16A-ΔCBM) from the marine Microbulbifer sp. BH-1 was cloned and expressed in Escherichia coli with pH and temperature being

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• Finkelmann et al. [30][31] and Ree et al. [14], we utilize the automated approach to compute CM5 atomic charges from semiempirical tight-binding (GFN1-xTB [37]) calculations. We modify the workflow to enhance the accuracy of the computed CM5 atomic charges. Instead of generating a single random conformer, we

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• applying the shear-flow method, negatively charged nanofibers of DA11 were assembled into a macroscopic soft scaffold when the solution was ejected into a shallow pool of calcium chloride solution (150 mM, Figure 4a). The high binding affinity between calcium ions and carboxylate groups enabled charge

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• -translational modifications by specific tailoring enzymes [5][6]. This precursor peptide substrate can be subdivided into multiple segments including 1) an N-terminal leader or recognition sequence used for binding by the tailoring enzymes and 2) a core peptide that is targeted for modification by the

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• photoswitchable tools, few photochromic lectin ligands have been developed. We have designed and synthesized several O- and S-galactosyl azobenzenes as photoswitchable ligands of LecA and evaluated their binding affinity with isothermal titration calorimetry. We show that the synthesized monovalent glycoligands

• due to stronger unfavorable entropy, they are in general of lower affinity. The validation of this proof-of-concept and the dissection of thermodynamics of binding will help for the further development of lectin ligands that can be controlled by light. Keywords: carbohydrates; glycosyl azobenzenes

• bacterial infections occur by adhesion to host tissues through receptor–ligand interaction between bacterial carbohydrate-binding proteins (lectins) and oligosaccharides at the host cell surface. Pseudomonas aeruginosa (PA), a Gram-negative, opportunistic and ubiquitous environmental bacterium, is known as

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• binding motif can be used to predict C2-type KRs [9]. These conserved motifs have been widely used to predict the stereochemical outcome of modular cis-AT PKSs and have facilitated bioinformatics-guided structural determination of complex polyketides [12][13][14][15][16][17]. However, despite being widely

• the active site resides, and a structural subdomain (KRS) with a truncated Rossmann fold that lacks NADPH binding sites and solely provides structural support by forming a heterodimer with KRC [24][25][26]. In δ-modules, an ER domain is inserted between KRS and KRC. Phylogenetic analyses of KRC and

• catalytic groove. The sequence logo of C0/C1-type KRs showed that some of them possess the catalytic Y (9), but such KRs instead possess mutation in NADPH binding site (Figure S3 in Supporting Information File 1). In C2-type KRs, we found that most C2-type KRs possessed the catalytic Y (9), but some