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

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• ]. Along with this, photoisomerization is described in patent literature [71][72][73][74]. It was shown that the experimentally observed enthalpy of isomerization (0.928 kcal/mol [47]) is in agreement with the calculated difference in the total energy of the two isomers (0.959 kcal/mol [65][75]). Cis-1,2

• -difluoroethylene was shown to have a lower energy compared to trans-1,2-difluoroethylene, which is in accordance with previously described 1,2-dihalogenated ethylene species [47]. The authors of reference [47] explained the higher stability of (Z)-HFO-1132 as follows: Within the family of 1,2-dihaloethylenes, when

• going from diiodo- and dibromo- to dichloro- and difluoroethylene, the radius of the halogen atom decreases while the electronegativity increases. As a result, the influence of halogen atom electronegativity on the double bond is more significant in 1,2-difluoroethylene, and the relative energy of the

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

• reaction condition temperature using Gaussian 16: SMD(THF)-PBE0/def2-TZVP // SMD(THF)-PBE0/def2-SVP, def2-TZVP(Cs) at 50 °C (w/MeOPPh3+) or 90 °C (w/Cs+), utilizing Goodvibes to calculate thermochemistry. The energy of the N1- and N2-tautomers of 6 differ by 3.1 kcal/mol at 50 °C, favoring the N1-tautomer

• , presumably due to entropic penalties. Three of four computed resonance forms were all found to be of approximately equal energy. Only the E-enolate form 6 (-N1H-E) was slightly higher in energy by 0.06 kcal/mol likely due to electrostatic destabilization of the oxyanion with N2, however, this difference is

• negligible. These data suggest that deprotonation occurs prior to alkylation and that deprotonation of either indazole tautomer leads to anions of identical or highly similar energy. Furthermore, as seen in Figure 4, a total, five coordinated complexes were found to be at least 4.5 kcal/mol more stable than

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 facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• /alloxazine photoredox catalysis [9][14][15][16][17][18][19], 7-methoxyderivatives should also be considered due to their absorption closer to the visible light region. This allows longer wavelength LEDs with lower energy photons to be applied, potentially contributing to avoiding undesired reactions [14][15

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• distributions of five molecular properties: highest occupied molecular orbital (HOMO) energy, lowest unoccupied molecular orbital (LUMO) energy, HOMO–LUMO gap (Gap), adiabatic ionization potential (AIP), and adiabatic electron affinity (AEA). As shown in the violin plots in Figure 3B, for all properties, the

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

• performed using AlphaFold 2.0 [52] in its CoLab online service [59], with default parameters. Each model underwent energy minimization in Chimera [60]. Subsequently, these models were analyzed in SWISS-MODEL [61] to obtain Ramachandran analysis. Finally, structural alignment was performed using PyMOL for

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• their highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels can be derived via the oxidation onset potentials as shown in the literature [51]. The electrochemical properties of all products are summarized in Table 5. Individual CVs, with onset potentials

• absorption bands are associated with π–π* and n–π* electronic transitions. The optical bandgap (Eg-opt) values of the compounds determined from the absorption edge of the solution spectra are also summarized in Table 5. Although both HOMO and LUMO slightly vary between the compounds, the energy differences

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• , accessing strained molecules continues to pose a synthetic challenge because many reported methods require harsh conditions for the preparation. An attractive alternative to traditional synthesis can be found in photochemical methods, bypassing energetic constraints by the utilization of photon energy. Thus

• functionalization step such as a ring-opening event is implemented, facilitated by the pre-installed strain energy of the four-membered ring [5][6][7]. The implementation of a build and release strategy, as depicted in Scheme 1a, necessitates the full compatibility of both individual reaction steps, thus placing

• demonstrated that the build and release of strain energy can be combined in a simple reaction sequence when appropriately tuning the reaction parameters. Our system relies on a photochemical Norrish–Yang cyclization of α-aminoacetophenones, which provides a sustainable entry to highly strained azetidinols. It

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 toxic agents such as MeI, TFA, or sodium cyanoborohydride can be harmful to both health and environment. Additionally, the need for constant protection and deprotection steps is time-consuming and results in low atomic economy, while also increasing the use of solvents, energy, and chemicals

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• . Romão Ramalho, 59, 7000-671 Évora, Portugal 10.3762/bjoc.20.145 Abstract A new paradigm for energy is underway demanding decarbonized energy systems. Some of them rely on emerging electrochemical devices, crucial in hydrogen technologies, including fuel cells, CO2 and water electrolysers, whose

• Decarbonized energy sources are the new paradigm in a world with increasing energy demands, primarily powered by fossil fuels, being proposed as a key strategy for restricting the detrimental effects of climate change. Vast efforts are being made to fulfil this crucial challenge of the 21st century. Clean

• , renewable, and environmental-friendly technological processes are being considered using electrochemical devices which convert chemical to electric energy and/or vice versa that, when associated to renewable energy sources, can promote sustainable energy systems [1][2][3][4]. Among them are included proton

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

• XGBoost. They trained on experimental pKa values in 39 solvents from the “internet Bond-energy Databank” (iBonD). Thus, they could predict the lowest pKa value for a wide range of molecules that contain bonds such as N–H, O–H, C–H, S–H, and P–H. However, they reported a scarcity of non-aqueous pKa values

• identify the lowest-energy conformer. We then conduct re-optimization in ORCA (v. 5.0.4) [22][23], using the dispersion D4-corrected DFT functional CAM-B3LYP [24][25], the Karlsruhe [26][27] triple-ζ basis set, def2-TZVPPD, and the conductor-like polarizable continuum model (CPCM) [28] as the implicit

• methods are evaluated as single-point calculations or optimization and frequency calculations. For comprehensive details, refer to Supporting Information File 1, section “Benchmark study - computational methods”. Hereafter, we check the geometries for imaginary frequencies and use the total thermal energy

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

• Abstract In the design of photoharvesting and photoresponsive supramolecular systems in aqueous medium, the fabrication of amphiphilic photoswitches enables a noninvasive functional response through photoirradiation. Although most aqueous supramolecular assemblies are driven by high-energy and biodamaging

• ; visible light; Introduction Solar energy is of paramount importance to life on the earth for various reasons, such as maintenance of a stable temperature and enabling photosynthesis as the basis of the food chain. Inspired by the natural photosynthetic processes, synthetic molecules were designed and

• functionalized with photoresponsive and photoabsorbing functional motifs, serving as the counterpart of natural photosystems. This allowed to construct smart materials that harvest light energy, e.g., solar cells, photosensitizers, and photochromic materials [1][2][3][4]. Supramolecular assemblies are commonly

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• reported by our group, was elucidated via quantum chemical calculations using density functional theory. The chlorination mechanism using PIFA and AlCl3 demonstrated a better experimental and theoretical yield compared to using PIDA. Additionally, the lowest-energy chlorinating species was characterized by

• energy than our proposed species. The reaction mechanisms are described in detail in this work and were found to be in excellent agreement with the experimental yield. These initial results confirmed that our proposed mechanism was energetically favored and therefore more plausible compared to

• points along the potential surface energy of the possible chlorination and bromination pathways studied in this work, Br and I atoms were treated with the revised version of the LANL2DZ basis set and effective core potential, referred to as LANL08(d), providing d-type polarization functions. Meanwhile

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

• crystallographic data using the 3-fluoropyrrolidinium cation and 3-fluoropyrrolidine. Subsequently, we explored the relative energy of all favored conformations of all different stereoisomers of 2,3-, 2,4-, and 3,4-difluoropyrrolidines at the B3LYP-D3BJ/6-311++G** level. A generalized anomeric effect, arising from

• pyrrolidinium salt [11] with the CCSD/DGTZVP geometry of the pyrrolidinium cation (with an exclusively axial C–F bond) and the energy of 3-fluoropyrrolidine conformations. Various combinations of DFT methods (B3LYP-D3BJ, ωB97XD, and PBEPBE) and basis sets (DGTZVP and 6-311++G**) were evaluated. The selection of

• these functionals was based on whether or not they included dispersion terms that could influence the absolute energy. These functionals are widely used and have demonstrated strong performance in numerous evaluations and validations across the literature. Similarly, for the basis sets, a comparison was

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• Science and Advanced Chemical Energy Research Center, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Japan PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan 10.3762/bjoc.20.139 Abstract An electrocatalytic hydrogenation of

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• ent-3aa-ent-3na, 1H, 13C NMR spectra of 3aa–na, 1H NMR of ent-3aa–ent-3na and their HPLC traces and single crystal data of ent-3ba. Acknowledgements The authors are thankful to Ms. Ketki Lele for her help in some preliminary experiments. Funding The authors thank the Department of Atomic Energy (DAE

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• electrophotochemical transition metal catalysis [26][27][28][29][30][31] as a unique and powerful synthetic platform for radical decarboxylative functionalization of aliphatic carboxylic acids [32][33][34][35][36][37]. In particular, the commonly required high activation energy for radical decarboxylation was provided

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

• rather similar Kd values. In order to rationalize this difference in binding mechanism, molecular models were obtained for selected low-energy conformations of E- and Z-isomers of a “model” scaffold of the para-azobenzene derivative in the binding site of LecA (Figure 5), by simple superpositioning of

• enthalpy (ΔH), and stoichiometry (n). Values for free energy change (ΔG) and entropy contributions (TΔS) were derived from the equation ΔG = ΔH − TΔS = − RT ln Kd (with T = 298.15 K and R = 8.314 J mol−1K−1). General procedure I for the O-alkylation with BrCH2CH2NHBoc: A solution of glycosyl azobenzene

• represents a ΔG value of −30 kJ/mol, corresponding to a Kd of approx 5 μM in the experimental conditions. (B) Manual docking of scaffold for compound 3 with selected low energy conformations of the E-isomer (yellow sticks) and Z-isomer (cyan sticks) superimposed on conserved position of galactose in all LecA

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• ] and many more (Figure 1). On the other hand, with unusual geometry and high reactivity norbornadiene and benzonorbornadiene derivative bicyclic compounds attract great attention by researchers with their use as building blocks in different application areas such as polymers, solar energy storage

Predicting bond dissociation energies of cyclic hypervalent halogen reagents using DFT calculations and graph attention network model

• Yingbo Shao,
• Zhiyuan Ren,
• Zhihui Han,
• Li Chen,
• Yao Li and
• Xiao-Song Xue

Beilstein J. Org. Chem. 2024, 20, 1444–1452, doi:10.3762/bjoc.20.127

• ][45][46][47] have highlighted the critical role of bond dissociation energy (BDE) in understanding the group transfer capabilities and chemical stability of hypervalent iodine(III) reagents. In this context, detailed knowledge of the BDE of hypervalent bromine(III) and chlorine(III) reagents is

• iodine [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76] and the computational database of organic species by Paton and co-workers [77], geometry optimizations and single point energy calculations for homolytic BDEs are both performed using M06-2X/def2-TZVPP [78][79][80] in the gas phase

• stabilize cyclic hypervalent bromine(III) and chlorine(III) reagents. In addition, we also calculated the heterolytic BDEs of cyclic hypervalent halogen reagents [46][47] to comprehensively examine the strength of chemical bonds (Table 2). Geometry optimizations and single point energy calculations for

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• halogen-bond formation by the linear combination of the % p-orbital character on the halogen and energy of the σ-hole on the halogen-bond donor. Keywords: aryl halide; diarylhalonium; halogen; halogen bond; non-covalent interaction; Introduction Halogen bonding has emerged as an important attractive

• that, for a set of monovalent iodine-based halogen-bond donors, a linear combination of σ-hole and σ* energy provides a superior predictive ability than σ-hole alone [26]. In this work we compare a set of both monovalent and nominally hypervalent halogen-bond donors in which the central halogen atom is

• Cl, Br, I, and At. We have used density functional theory (DFT) to uncover periodic trends in the orbitals used by the central halogen atom in forming covalent and non-covalent interactions and how this impacts the interatomic distance and energy of halogen-bond interactions (Scheme 1c). Results and

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• heightened by the current energy crisis and the adverse impacts of industrialization. The development of green and energy-efficient methods in organic chemistry that use renewable sources of starting materials is considered highly sustainable [1][2][3]. Radical reactions have profound applications in organic

• synthesis [4][5][6][7][8][9]. In the context of sustainable catalysis, visible-light-mediated chemistry is becoming a prominent viable option for radical transformations in the synthesis of biologically useful compounds due to the energy efficiency and environmental friendliness [10][11]. Recently, the

• catalysis In recent times, visible-light-mediated photoredox chemistry has evolved as a unique tool for various organic transformations. In contrast to traditional catalysis, the photochemical process uses an electron or energy transfer mechanism to form reactive intermediates. Typically, a photocatalyst is

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• hyperconjugation via bending the exocyclic methyl group such that the formal p-orbital at C3 no longer aligns with the C2–C7 bond results in the 6/6/6-tricyclic C3 tertiary cation B2+, which is 13.0 kcal mol−1 higher in energy. In principle, either A2+ or B2+ could be deprotonated to form products. A similar

• energy profile is seen for protonation-induced cyclization of 1, although the 6/6/6-tricyclic C3 tertiary cation is 7.1 kcal mol−1 higher in energy than its preceding intermediate (Figure 2C). A lower energy conformer of 1 exists, but we have been unable to find the corresponding cation A1b+, which

• [22]. An X-ray structure of 9 allowed us to solve its absolute configuration and measure the C2–C7 distance to be 3.31 Å. This distance matches reasonably well with the calculated distance, 3.36 Å, of the lowest energy conformer of 9. Calculation of the proposed 6,7-epoxy derivative of 2, which was

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• Diels–Alder reactions and can be used repeatedly without significant degradation. These materials also allow the reaction to be completed in less time, with less energy consumption and higher yields. Keywords: biobased solvent; epoxyisoindoles; furanics; green chemistry; intramolecular Diels–Alder