Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• . Interestingly, only one conformer is observed, with both perfluorobenzyl groups pointing in the same direction (instead of the opposite directions) on the ANTH core, in contrast with the earlier reported by us presence of two different conformers of perfuorobenzylated corannulene in the single crystal, which

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• strong reinforcement of the geometrically preferred C5 conformer by coinciding pyridyl groups with “out” carbonyls. The result is a lowering of symmetry from D3h to CS. While observations of symmetry-lowering are commonplace in controlled environments [47][264][293][335][366][367][368][369], we believe

• positions of the two active carboxylic acid groups in cages such as 1, there are several levels of tuning possible in terms of the rigidity. Hexapyridine cage 2 is calculated (and observed) to exist exclusively (>99.9%) in the C13 conformer (Figure 8B and Figure 9A) [41]. Since the amide groups rarely

• conformers C5, C9, C10, C12, and C13. (B) Organocatalysis performed by cage 2 (which exists exclusively in the C13 conformer) is a clear example of polarization and organization. The data for cage 1 suggest cavity height (balanced flexibility) is important for the catalytic rate. Supporting Information

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• on forces and step size. The IEFPCM solvent model [33] was used to simulate the solvent effects of methanol and frequency calculations were used to determine the conformers as minima. Conformers 4.5 kcal/mol above the lowest energy conformer and double conformers were discarded. Time-dependent DFT

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• HB complex. Values for ΔGcalc were then calculated as the weighted average of the free energy of each HB complex as in which PMe3PO···HB,a and PMe3PO···HB,b are the percent populations of the HB complex of Me3PO with the donor conformer a and b, respectively; PMe3PO | HB,a and PMe3PO | HB,b are the

• percent populations of Me3PO and the corresponding HB donor conformer as two non-interacting molecules (see Supporting Information File 1 for details). We found a strong linear correlation between ΔGexp and ΔGcalc obtained at the PCM(MeCN)-M06-2X/6-31+G(d,p) level of theory (Figure 5 and Figure 6A). These

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• the two conformers of hydrazones 3e and 3f (see Supporting Information File 1) is in accordance with the E stereoisomers. Furthermore, another correlation is observed for one conformer involving the NH of the imine on one side and the α-proton and the CH2 of the Cbz of the phenylalanine on the other

• . This correlation is present for one conformer (anti) and not for the other (syn), and this observation is similar for hydrazones 3e and 3f (see Supporting Information File 1). Based on these experimental data we can hypothesize the geometry of the two conformers of hydrazones 3e and 3f is E,syn and E

• not the enamine. As for the hydrazones 3e and 3f, we assumed that the hydrazones 6e and 6f were obtained as a mixture of conformers, E,syn and E,anti (Scheme 4). Surprisingly, the ratio of each conformer differs for hydrazones 6e (ratio 77:23) and 6f (ratio 52:48). The last cyclization step was based

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

• stated above, all analogues exhibit a gt conformation except for compound 17, which is a tg conformer. This information could also be extracted from Table 3 by looking at the O5–C5–C6–O6 torsion angles (Table 3, entry 1). Table 3 also highlights that there are significant intra-annular torsion angles for

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

• structure, it is important to include information from relevant conformers. To avoid losing important information from discarding conformers, Paton and co-workers [85] introduced wSterimol, which takes into account structures from the entire conformer ensemble via Boltzmann-weighting. The authors used their

• descriptors for the prediction of the enantioselectivity for several previously reported reactions, showing improved prediction performance compared to non-Boltzmann-weighted Sterimol parameters. Apart from considering parameters of the entire conformer ensemble, it has been shown that informative models can

• minimum buried volume in a conformer ensemble was identified to determine the ligation state towards a metal centre as either mono- or bis-ligated and thus providing a threshold for catalytically active ligands [87]. All of these examples demonstrate that not only the type of descriptor is important, but

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

• : Allostreptomyces; β-alkylpyrrole; conformer; cytotoxic; DFT; 4-formylpyrrole-2-carboxylic acid; Introduction β-Alkylpyrroles are key structural motifs in biomolecules and functional organic materials [1]. For instance, β-alkylpyrroles are the main building blocks for the life-essential tetrapyrrole pigments

• and 3, their conformational ensembles, datasets of a structure and population of each conformer [25], were determined using a Spartan 24 parallel package conformational search tool (Wavefunction Inc, USA), followed by geometry optimization of the most weighted conformers (Boltzmann distribution weight

• lower to 0.004). Eleven and seven weighted conformers for compounds 2 and 3 were obtained, respectively, each forming equilibrium mixtures. The quantum chemical method for the calculation of conformer distribution was ωB97X-V/6-311+G(2df,2p)[6-311G*] [30]. The CPCM solvation model for methanol was used

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

• given SMILES string undergoes modifications to produce a list of SMILES for each deprotonated C–H bond. We generate min(1 + 3nrot, 20) conformers for each SMILES using RDKit (v.2022.09.4) [16][17], where (nrot) represents the number of rotatable bonds. Each conformer undergoes optimization in dimethyl

• 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

• 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

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

• the impact of gauche and anomeric effects on the conformer stabilities of different stereo- and regioisomers. Initially, we conducted a benchmark assessment comparing the optimal density functional theory method with coupled cluster with single and double excitations (CCSD) calculations and

• hyperconjugative interactions [3]. However, it is noteworthy that 3-fluoropiperidine does not exhibit such a fluorine gauche effect. In this case, the axial conformer is similarly populated to the equatorial conformer, despite the favorable antiperiplanar arrangement of orbitals that would facilitate these

• delocalization is considered to be secondary [7]. However, stabilization via intramolecular hydrogen bonding does not seem to significantly impact the conformational stability of 3-fluoropiperidine. In this context, the cis-conformer, with the axial fluorine atom facing the N-hydrogen atom, is either equally or

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

• 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

• implies that protonation and cyclization may be concerted for that conformer (Figure S4, Supporting Information File 1). We previously transformed 2 into the trans,trans-6/6/6-tricyclic C6 alcohol 8 using mCPBA to epoxidize the C6–C7 alkene [7]. Under the same conditions, epoxidation of 1 yielded the 6,7

• [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

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• the PBE1PBE/6-311+G(2d,p) level of theory using the DFT B3LYP/6-311++G(d,p) optimized geometries (DMSO solution) and applying a multi-standard approach [44]. The calculated shifts of sp2-atoms C-7a, C-4, C-6, C-3, and C-3a in (Z)-8 and the s-cis-conformer (with respect to the C4–N bond) of 9 were

• model showed that (Z)-8 was significantly less stable than the s-cis-conformer of 9 in DMSO solution (ΔG = 7.17 kcal/mol; 298 K, 1 atm). As we proposed, pyrazolopyrimidine 8 undergoes dimerization to produce macrocycle 5 under certain conditions (Scheme 5). The dimerization of 8 was thoroughly studied

• calculated by the GIAO method at the PBE1PBE/6-311+G(2d,p) level of theory using the DFT B3LYP/6-311++G(d,p) optimized geometries (DMSO solution) and applying a multi-standard approach [44]. It is noteworthy that, in the most stable conformer of 10, the NH2 group of the triazole ring is located between the

Benzoimidazolium-derived dimeric and hydride n-dopants for organic electron-transport materials: impact of substitution on structures, electrochemistry, and reactivity

• Swagat K. Mohapatra,
• Khaled Al Kurdi,
• Samik Jhulki,
• Georgii Bogdanov,
• John Bacsa,
• Maxwell Conte,
• Tatiana V. Timofeeva,
• Seth R. Marder and
• Stephen Barlow

Beilstein J. Org. Chem. 2023, 19, 1651–1663, doi:10.3762/bjoc.19.121

• that the sample represents neither solely a high-symmetry conformer, nor a mixture of rapidly exchanging lower symmetry conformers. In the case of 1b2 all the proton resonances are rather broad, and variable-temperature experiments (see Supporting Information File 1, Figure S2) showed further

• reported Y = ferrocenyl derivative, 1c2 [14], or the molecule in the structure 22 [35], all three of which also have Ci symmetry. The other conformer present, although also staggered, has no crystallographic, or even approximate molecular, symmetry and is characterized by a Y–C–C–Y torsion angle of 60.3

• mostly somewhat folded towards a puckered envelope conformation, generally with the Y group in a pseudo-axial position and the 1,3-methyl groups and the central C–C bond in pseudo-equatorial positions, although for one of the monomers in the unsymmetrical conformer in the structure of (N-DMBI)2, 1b2, the

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• ′, and 24 conformers for 3. The geometry of each conformer was optimized using DFT calculations at the B3LYP/6-31G(d) level of theory [20][21] with the conductor-like polarizable continuum model (CPCM) solvent model (MeOH) and Gibbs free energy was calculated subsequent frequency calculations. Time

• -dependent (TD)-DFT calculations at the B3LYP/6-31+G(d,p) level with CPCM solvent model (MeOH) [22] were performed for the optimized conformers. The resulting ECD spectra calculated for each conformer were averaged using Boltzmann populations evaluated at 300 K from Gibbs free energy calculated from the

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• porphyrin subunits and was more efficient in DMSO as compared to chloroform. Also, a clear evidence of a folded conformer was found by electrostatic and CH–π interactions, which was also, confirmed by density functional theory (DFT) calculations. In another report, meso-triazole-bridged porphyrin-carborane

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• main product [36]. Based on molecular mechanics calculations, four conformers 1a–d have been described for 1 (Scheme 3B) [37]. The calculations revealed all four conformers are of similar stability, with 1a being the most stable conformer. The fact that 1 shows a defined set of fifteen sharp signals in

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• rationalized by the greater steric repulsion in the conformer of the respective oxyanion leading to the anti diastereomer compared to that from which the major, syn diastereomer is formed (Scheme 5). Notably, a compound analogous to 5a was synthesized with thiophenol in 78% yield. However, it turned out to be

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• -stereogenic center, which bears a methyl group, the electrophilic site (the iminium ion), and two possible nucleophilic sites (a prenyl group and a trisubstituted alkene within a cyclohexene ring). In conformer 12a, the prenyl group occupies a pseudo-axial position, the methyl group occupies a pseudo

• -equatorial position, and the trisubstituted alkene within the six-membered ring serves as the nucleophile. It is important to note that in this chair-like conformer, the ethyl ester group at C2 assumes a pseudo-equatorial position. Although an alternative boat-like conformer is also possible (which would

• of the 3-azabicyclo[3.3.1]nonane ring system. In any case, this aza-Prins reaction is by far the preferred mode of cyclization of iminium ion 12 based on the isolated yield of 8 (64%), ultimately leading to the carbon skeleton found in the natural product halichonic acid ((+)-1). In conformer 12b

Comparison of crystal structure and DFT calculations of triferrocenyl trithiophosphite’s conformance

• Ruslan P. Shekurov,
• Mikhail N. Khrizanforov,
• Ilya A. Bezkishko,
• Tatiana P. Gerasimova,
• Almaz A. Zagidullin,
• Daut R. Islamov and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1499–1504, doi:10.3762/bjoc.18.157

• trithiophosphite have been considered quantum-chemically (Figure 2, Table 1): trans-trans-trans (ttt), gauche-trans-trans (gtt), gauche-gauche-trans (ggt), and gauche-gauche-gauche (ggg). During optimization the ggt conformer adopted a cis-gauche-trans conformation with Fc(C)–S–P lone pair dihedral angles of 8

• °, −60°, and 173°, respectively (Table 1). The lowest energy has been predicted for the gtt conformer, nevertheless the energy differences between the gtt and cgt conformers are negligible (0.23 kcal/mol). Interestingly, the cgt conformation has been found previously for tricymantrenyl trithiophosphite

• [19]. The highest relative energy is predicted for the ggg conformer (1.7 kcal/mol). The ferrocene adopts an almost eclipsed conformation in all the models with the dihedral angle between two Cp rings of ≈ 10°. Our previous work indicated that Cp can rotate at room temperature [20]. The Fc(C)–S–P lone

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• the 2 kJ/mol energy window were generated and optimized using DFT calculations at the B3LYP/6-31+G (d,p) level. Frequency calculations were performed at the same level to confirm that each optimized conformer was true minimum and to estimate the relative thermal free energy (ΔG) at 298.15 K. The two

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• -house code which modifies parameters for cations from existing parameters for neutral molecules. For each intermediate in the reaction mechanism (path HP and IE) we created 100 conformers which were subsequently clustered (a cluster width of 1.0 Å was used). For each unique conformer we performed QM

• calculations and then chose the lowest energy conformer as representative of each carbocation intermediate in the mechanism. Hence, each intermediate state is represented by a single conformer, which is the lowest energy conformer found. Quantum chemistry calculations Optimizations and subsequent frequency

Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• , H-3b/H-2b; H-6/H-3b/H3-15 suggested that H-6, H3-14, and H3-15 were positioned in the same orientation. To confirm the relative configuration of C-8 in 2 was determined using a DP4+ statistical analysis [13]. The DP4+ protocol was applied to the simulated 13C NMR chemical shifts of the conformer 2a

• based on the Boltzmann populations of each conformer in the associated Gibbs free energy (Supporting Information File 1, Figure S45). The ECD spectra were Boltzmann-weighted and generated using SpecDis software (Version 1.71) [23] with a σ/γ value of 0.30 eV. The chemical shift values were calculated

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• imidoacetal D. Due to free rotation of the (O,N,N)C–C(NO2) axis the suitable conformer E can be formed. Thus, the less hindered NH group of intermediate E interacts with the C3 position giving an intramolecular, five-membered addition product F. Upon elimination of HCl from F by means of the second equivalent

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• . Interestingly, the molecule does not bear any pseudo-mirror plane, that is, the observed conformer is asymmetric (C1) in itself, regardless the configuration of the two sulfinamide substituents. This peculiarity is likely due to the hindered rotation across the newly formed C–C bond, joining the two oxindole

• conformer. Aiming to generalize the discovered transformation, a brief scope of the reaction with respect to the N-tert-butanesulfinyl imine substrate was next performed (Figure 2). The protecting group R1 on the oxindole nitrogen atom was found to have a moderate effect on the reactivity, with R1 = Bn

• ) and one sulfinamide oxygen (O4). Atom numbering as in Figure 1. The asymmetry of such interactions reflects the intrinsic asymmetry of the solid-state conformer. Supporting Information Supporting Information File 42: Experimental part, NMR spectra and christallographic data of compound 2a.

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• high symmetrical geometry. Finally, a single broad peak for the four methoxy groups ($) appears at 2.96 ppm. In analogy with parental diureido and dithioureido calix[6]arenes, we were able to observe the presence of a second minor cone conformer, in a ≈4:1 ratio, highlighted by the presence of a second