Homogeneous continuous flow nitration of O-methylisouronium sulfate and its optimization by kinetic modeling

• Jiapeng Guo,
• Weike Su and
• An Su

Beilstein J. Org. Chem. 2024, 20, 2408–2420, doi:10.3762/bjoc.20.205

• with increasing H2SO4 mass fraction, which aligns with the findings from previous studies on mixed acid-catalyzed nitration reactions [32][33]. However, the data also reveal a decline in rate constants when the H2SO4 mass fraction exceeds 94%, suggesting a complex interaction at higher acid

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

• in a Mannich reaction [4]. In 2018, our group showed in a proof-of-principle study [5] that the Lewis acid catalysis by DAI salts is based on halogen bonding (XB), an interaction between a Lewis base (XB acceptor) and an electrophilic halogen atom in the Lewis acid (XB donor) [6][7][8][9][10]. In

• ) Å, 84% of Σr, and C1–I1···Br1 = 176.08(9)°]. The bond distances indicate that the hydrogen bond is noticeably weaker than the two XBs and thus constitutes merely an assisting interaction. The XB interactions in this crystal structure were compared to the ones in the literature-known co-crystal of

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• derivatives are used as ligands in the synthesis of metal complexes (Ni(II), Pd(II), Pt(II), Cu(I), Ag(I) etc.) exhibiting antibacterial and antitumor activity [34]. In most cases, polyfunctional catechol thioethers were obtained by Michael reaction via the interaction of o-, p-benzoquinone and the

• moiety. A feature of heterocyclic thiols used as starting reagents is the possibility of thiol–thione tautomerism which leads to the appearance of two nucleophilic centers: a sulfur or nitrogen atom. Therefore, in the case of their interaction with 3,5-di-tert-butyl-6-methoxymethylcatechol, the

• possibility of alkylation of the nitrogen atom in the heterocycle cannot be excluded. This alternative pathway is similar to the previously described interaction of the aforementioned catechol with 3,5-dimethylpyrazole or benzimidazole [55]. A study of the structure, electrochemical properties, anti

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

• 78 with a pending 4-pyrenyl group. The catalyst acts as H-bond donor but additionally it controls the chiral environment through π-stacking interaction with the aryl group of the substrate, blocking one of the enantiofaces of the iminium intermediate 79. The reaction proceeds in Et2O at −50 °C and

• interaction between the catalyst and the aryl group of the substrate in the enantio-determining step appears to affect the scope. Other problematic substrates included (Z)-α-methylcinnamyl and (Z)-α-bromocinnamyl acetals giving the respective products with lower ee. Despite some phenyl substrates with 3

• transfer reagents; (iv) direct metal-free imine carbanion addition to electrophilic alkene. Class (i) underwent an evolution from catalysis by covalent interaction to chiral hydrogen-bonded catalysis, which allowed the expansion of the allyl component scope from simple allyl to substituted allyl groups

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

• ][36][37]. A covalent bond between a probe and a protein is needed because of denaturing conditions used during the analysis. In contrast, relying on a noncovalent interaction would result in loss of the probe–protein interaction. The bioorthogonal handle is therefore essential for an enrichment or

• probe–protein interaction in native conditions in living cells. Taken together, the linkers used in chemical proteomics workflows are applied broadly in many research areas including screening of fragment libraries, covalent modifiers, protein PTMs, protein–protein interactions, protein–nucleic acid

• gel and subjected to MS analysis to identify the labeled proteins [77][78]. The in-gel analysis is often used for target validation with corresponding protein mutants or knockout cell lines, with loss of the identified probe–protein interaction leading to disappearance of the fluorescence band from

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

• of HFIP (Scheme 4). First, 1H NMR was employed to examine the interaction between HFIP and iminoiodinane 2c in CD3CN (compound 2c was chosen over 2a due to its increased solubility in nonprotic solvents). In a sample of 2c with 4 equivalents of HFIP, a broad signal for O–H proton of HFIP was observed

• at 5.52 ppm with a FWHM = 56.6 Hz (Scheme 4a). This resonance was broader and more downfield than that of free HFIP in CD3CN (5.41 ppm with FWHM = 5.0 Hz), suggesting a hydrogen bonding interaction between HFIP and 2c, and similar observations were also reported for the hydrogen bonding between HFIP

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• dispersion interaction between the DABCOnium system and the CPA is governing the exo-selectivity. For the application of the ML techniques discussed above, it is assumed that all studied reactions follow the same mechanism. If that is not the case, models cannot be reliably fit to the data points, similar to

• enantioselectivities (Figure 9B). In their model, molecules were represented as graphs, where local steric and electronic information was added to each node (atom). Additionally, the used graph neural network contains a molecular interaction module that allows the model to learn synergistic effects between molecules

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

• , the electrostatic interaction between the homogeneous catalyst and the support is robust enough to reduce leaching significantly [67][73]. However, a potential drawback of this technique is that the presence of a charged support can lead to complications, such as distortion of the catalyst structure

• does not require any interaction between the catalyst and the support. Because of this, it is the sole technique which attempts to mimic the homogeneously catalysed reaction process [75]. It typically results in enhanced properties, e.g., augmented morphological stability, tailored physicochemical

• ]. 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

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

• interaction with host proteins [5][6]. Notably, the complexity of the glycome far surpasses that of the genome, transcriptome, and proteome, not only due to the structural and conformational diversity of glycans, whose synthesis is not template driven, but also due to their dynamic nature [5][6]. Although

• computational tools have been developed to facilitate the prediction of protein binding sites. We report here only the applications related to the protein interaction with glycans: 1. PeSTo-Carbs [105]: it is an extension of Protein Structure Transformer (PeSTo) [106], a deep learning method to predict protein

• interaction interfaces with other proteins, nucleic acids, lipids, small molecules, and ions, starting from a protein structure. PeSTo-Carbs is specifically trained to predict carbohydrate and cyclodextrin binding interfaces on proteins. Two different modules are available: a general model PS-G for a wide

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• , facilitating their cyclization with intermediary formed hydrazones to yield 5-hydroxypyrazolines. After subsequent interaction with atmospheric oxygen, the product 65 is formed. This method exhibits a high degree of substituent tolerance, and aliphatic compounds generally lead to higher yields. A special

• HOMO (diazo compound)–LUMO (alkyne) interaction during the 1,3-dipolar cycloaddition [163], Wu et al. showed that electronic effects in this strategy do not influence the yield. In addition, sterically demanding reactants could be used in the method. Enhanced yields were achieved by using NaOEt and

Understanding X-ray-induced isomerisation in photoswitchable surfactant assemblies

• Beatrice E. Jones,
• Camille Blayo,
• Jake L. Greenfield,
• Matthew J. Fuchter,
• Nathan Cowieson and
• Rachel C. Evans

Beilstein J. Org. Chem. 2024, 20, 2005–2015, doi:10.3762/bjoc.20.176

• was seen on reverse isomerisation using blue light (Table S1, Supporting Information File 1), which may suggest that the larger micelle size in the E isomer is obtained by slow agglomeration over time. The interaction of ionising radiation, such as X-rays, with water is known to result in a radiolysis

• , respectively, with comparable dimensions to those in H2O (Tables S1 and S3, Supporting Information File 1). However, there is a large difference in the interactions between AAPTAB micelles on switching solvents, which can be seen as a decrease in the interaction hump in the SAXS pattern at Q ≈ 0.045 Å−1

• the samples ex-situ for 3.5 hours to achieve a Z-rich PSS, where the percentage isomerised has been determined previously using 1H NMR spectroscopy [20]. The 10 wt % sample was measured over 800 X-ray exposures of 250 ms each. The initial Z-rich PSS SAXS pattern shows a strong interaction peak at Q

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• [31]. Range-separated hybrid GGA (RSH-GGA) functional, including dispersive interaction with 6-31G* as the polarization basis set (ωB97X-D/6-31G* method), was used for energy and geometry optimization [32]. Bioactivity Cytotoxicity and tyrosinase assays were carried out according to the procedures

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 N1-product with highly similar energy (averaging −16.8 kcal/mol). The N2-s-cis and N2-s-trans TSs leading to the N2-product were higher in energy and led to the higher energy N2 products. The critical difference between N1-s-cis and N2-s-cis is the presence of the N2–Cs+–O non-covalent interaction

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• the substrate, and thus preventing the possible interaction between the amide moiety and PISA, as opposed to CH3CN. The olefin moiety of the complex then interacts with the exposed central iodine(III) atom in PISA [25], forming the intermediate D. Similar cyclic iodonium intermediates were also

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• equivalent nitrogen atoms (aN = 6.56 G) as well as additional triplet splitting provided by hyperfine interaction with a pair of equivalent protons (aH = 1.89 G). In contrast, only traces of this admixture were detected for the diarylamines with electron-withdrawing substituents. This is in line with our

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• ketenes 2 generated by a thermally promoted Wolff rearrangement [3]. The interaction of such ketenes with nucleophiles of different nature could serve as a source of libraries of structurally diverse 2-oxoazetidine-3-carboxylic acid derivatives 3 (Scheme 1). The 2-oxoazetidine-3-carboxylic acid

• the exocyclic carbonyl group by preformed ring contraction and interaction of the intermediate ketene with the selected nucleophile. Various aromatic and aliphatic amines as well as alcohols and thiols can be used as nucleophiles. 5-Monosubstituted diazotetramic acids give exclusively trans

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

• a [1,5]-H shift [19], indazolo[3’,2’:2,3]imidazo[1,5-c]quinazolin-6(5H)-one 18 (Scheme 7) [20]. The favorable host–guest interaction between 14 and the reactants (demonstrated by 2D NMR and FTIR spectroscopy as well as by scanning electron micrography), combined with the acidity of the succinyl

• its nucleophilicity and improving its orientation. Furthermore, Ser105 formed a strong hydrogen bond also with benzaldehyde, making it a better electron acceptor. Interestingly, also the imine intermediate showed strong interaction with Thr40 and Ser105 residues, so becoming a good electrophile for

• the addition of tert-butyl isocyanide. On the other hand, the addition of tert-butyl isocyanide on the imine altered the orientation of adduct 19, suppressing the interaction with Ser105 (Scheme 8). Very recently, Tyagi et al. reported the double encapsulation of CALB and Pd(PPh3)4 within silica

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• experimental MIBiG sequences, were processed in MEGA X [55]. The sequences were aligned using MUSCLE [56] with specific parameters: Open gap: −2.90, Extended gap: 0.00, hydrophobicity multiplier: 1.20, maximum interaction: 16, ensemble method (interactions 1,2): UPGMA, ensemble method (others interactions

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• the π-interaction involving two 8-Ph molecules pointed in the same nominal direction is not linearly aligned, but is instead twisted by 19°. This angle, likely enforced by the sterics of the phenyl groups, may be an interesting approach to inducing helical turns in supramolecular assemblies derived

• the longer interaction distances and interceding incorporation of CH2Cl2 (Figure 2b). Furthermore, in 8-Ph the interstack C=O···H–C interaction is skewed such as to involve only one C=O, compared to the symmetric dual-contact that is seen for 7-Ph. Optical and electronic characterization 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

• . According to the mechanism, the heterocyclic ring closes by the attack of the bulky radical -CO-HN• over the α steroidal side to circumvent the 1,3-diaxial interaction with the methyl group at C-10. Spiro-1,3,4-oxadiazoline steroid Shamsuzzaman et al. achieved the synthesis of 5’-acetamido-3’-acetyl-(3R

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• ]. A crystal structure was additionally obtained for tetrazine 1c. Bond lengths and angles were similar to those of known five-membered NHIs [25], including a strong intramolecular interaction between the nitrogen of the tetrazine and the hypervalent iodine atom (I1–N1: 2.44(4) Å; the sum of VdW radii

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

• 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

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• systems [5]. This conformational preference is attributed to an electrostatic gauche effect, where an attractive NH2+∙∙∙Fδ− interaction reinforces the well-known hyperconjugative gauche effect. Additionally, NH∙∙∙F hydrogen bonding has been proposed to play a role in stabilizing conformers of certain 3

• Figure 5 and Table 2. This disparity in stability was largely attributed to the relative orientation of the nitrogen electron lone pair and the adjacent C–F bond, facilitating an anomeric interaction characterized by nN→σ*CF electron delocalization. Isomer 2 also demonstrated such an orientation, but the

• , less stabilizing σCC→σ*CF interactions were anticipated. Moreover, besides the anomeric interaction, the pseudoaxially oriented C–F bonds in 17 and 19 facilitated efficient electron donation from vicinal antiperiplanar C–H bonds through σCH→σ*CF interactions (Figure 6). The methylene group separating

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

• 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

• reversible light modulation of their activity since each isomer shows distinct structural and electronic properties [13]. Photoisomerization-induced conformational and polarity changes may allow to increase or decrease the interaction with the target protein or receptors, then modulate the drug potency on

• different sizes and substituents are tolerated on the aryl aglycon, we decided to replace the aryl aglycon by photoswitchable azobenzene in both O- and S-galactosides (Figure 1B) to investigate their binding affinity and the influence of the photoisomerization on the lectin interaction. The ammonium group

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

• the sequence of both KR subdomains [13]. This suggests a strong domain–domain interaction between KR and DH, as observed in the structure of KR-DH-ER tridomain (Figure 2c) [24], and indicates that KRs in β-modules and γ/δ-modules may not be generally interchangeable for domain swapping. However, the

• KRC, the N-terminal helix αB and the lid region αFG located at the C-terminal of KRC (Figure 2d). Indeed, this lid region exhibits a direct interaction with the DH and DH-KR linker (Figure 2c). However, such interaction was not observed between the N-terminal helix αB and DH in the crystal structure

• of DH-ER-KR tridomain (Figure 2c). This finding suggests that the helix αB may have an allosteric interaction with DH or potential large conformational changes between DH and KR during catalysis. Sequence logo analysis of KRC from β-modules Based on the clear stereoselectivity-dependent clades