A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• . It contains a six-membered ring and is, like its five-membered correlate, known for its secondary structure inducing properties, which are particularly useful in the design of peptide conformations. We present a new and improved way to generate enantiomerically pure pipecolic acid derivatives with

• broad doublets instead of double-doublets (Figure 2a,b). The lack of a second coupling constant indicates a conformation in between a chair and a boat with a dihedral angle ϕ near 90°, which is necessary for a coupling constant to be around 0 Hz. Half-chair or twist-boat conformations are well known for

• being intermediate conformations in six-membered rings with dihedral angles ϕ near 90° (a front and side view of cyclohexane is shown in Figure S1, Supporting Information File 1). In case of a twist-boat conformation all dihedral angles for H2 would ultimately result in double-doublets for 3J(H2,H3,pro

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• previously isolated in crystalline form in two different molecular conformations [18]. In conformer I (Figure 2, bottom), all three benzyl groups are oriented towards the interior of the macrocycle. In contrast, conformer II (Figure 2, top) features two benzyl groups projecting inward and one benzyl group

• structures are analogous to the single crystal structure of the previously reported phenylalanine HIMs alone (Figure 2). For the 1/LiBArF20 crystal, the phenylalanine HIMs exists in two different molecular conformations analogous to I and II (Figure 6) with differences arising in the location of the

• difference in binding constants as well as the isolation of two distinct molecular conformations of phenylalanine HIM 1 (Figure 1), DFT calculations were performed. The details of DFT calculations are shown in Table 1. For DFT calculations, we assigned two HIM macrocycles per LiBArF20 as found in the co

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• study the diverse or similar properties between the antiaromatic molecules a and b, in which the main difference is the presence of a third aromatic ring. According to the literature, the presence of the third benzene ring in the TBA (a) differentiates the conformations of structures a and b in the

• , making it a promising candidate for new PC designs. While TBA and IMD displayed similar characteristics, the D–A IMD compound showed a shorter lifetime, which proved unfavorable in photocatalytic tests. The differing excited state conformations (bend vs planar) reported for these azepine analogs did not

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• importance. Despite the development of a number of receptors for dicarboxylates [21][26][27], their recognition remains a challenging task due to their strong hydrophilicity (−400 kJ/mol) [28][29], dispersed negative charges at both ends, complex shapes, and flexible conformations. Moreover, the similar

• interactions, the host undergoes conformational adjustments: the distance between the two submacrocycles increases, and the glycol chains adopt extended conformations compared to the structure shown in Figure 1. These results suggest that the experimentally observed strong binding capability and selectivity of

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• with a sizable barrier of 15.0 kcal·mol−1 via TS 8 (Figure 4), interchanging two almost equienergetic conformations of 11 (11Z, with an N–N–C–CEt torsion angle of 32°, and 11E, with an torsion angle of 111°), which have a strong reminiscence of their predecessors' former geometric isomerism, an effect

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• results were submitted to a MM-GBSA calculation (molecular mechanics with generalized Born and surface-area solvation) [50] leading to the binding energies of the different isomers of 1, 2, 4, and 5 for both protein conformations (Table 3 and Supporting Information File 1, Tables S13–S18). The determined

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• is flexible and the two senses of helicity – and other conformations – undergo rapid equilibrium rendering the C1 and the C1·Me6CHDA complex achiral. The centroids of the aromatic sidewall are 0.9698 Å (1.1193 Å) above and 1.3090 Å (1.4832 Å) below the mean plane of the glycoluril methine and

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• target binding will incur little entropic cost) and high selectivity (since off-target interactions will be minimised) [1]. There are several methods by which the conformations of small molecules can be controlled, but in this review we will focus upon one particular method, which is the installation of

• compared to the non-fluorinated stearic acid 12 (Figure 3) [26]. If two fluorines are introduced into the middle of an alkyl chain in a 1,2-pattern, several competing factors arise that can influence the molecular conformation [27]. One factor is hyperconjugation: conformations in which the σ*C–F orbitals

• are aligned with either σC–H orbitals (II, Figure 3), or, to a lesser extent, σC–C orbitals, will be favoured. Another factor is simple sterics: conformations in which the flanking alkyl moieties are further apart from one another will be favoured. A third factor is polarity: for example

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

• , whereas 9,10-ANTH(BnF)2 loses vibronic structure in the emission spectrum. This may be the result of different conformations upon relaxation [31]. The HOMO–LUMO gap (Eg) decreases from ANTH (3.28 eV) to 9,10-ANTH(BnF)2 (3.05 eV). A decrease in Eg is regarded as one of the methods for improving the

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

• rare example of a cavity-promoting catalysis via both “organization and polarization” (Figure 4C), including dual activation [105], albeit with vague directionality (the substrate can be productively oriented in many conformations). This directionality might be advanced by new capsule types. For

• reductive amination to stabilize imine cages, and the resulting amine cages gain solubility from increased flexibility at the cost of losing some structural rigidity [42][43][44]. Metastable conformations – programming cavity shape and symmetry: Unlike non-covalent/dative assemblies, covalently linked cages

• ]. In this approach, symmetric topologies undergo a natural symmetry-lowering process when the restricted angles possible in a polymacrocycle environment lead to non-symmetric conformations in the pursuit of equal strain distribution. In the case of cage 3e, the mixed pyridyl/aryl system results in a

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• pathway. The benchmark for the SN1 spectrum of the mechanistic continuum has been elaborately illustrated and supported by Codee et al. by mapping full ensemble of conformations that the glycosyl oxocarbenium ions can adopt by a complete conformational energy landscape (CEL) study in a quantitative manner

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• analysis of it with X-ray crystallography. Interestingly, it is observed that tris(4,5-dehydro-2,3:6,7-dibenzotropone) crystallized from its solution in hexane resulting in colorless and yellow crystal polymorphs, where it adopts conformations of approximate Cs and C2 symmetry, respectively. Furthermore

• conformations of approximate Cs and C2 symmetry, respectively. Furthermore, the expansion of the π-skeleton of 1 through the Barton–Kellogg and Scholl reactions enabled the synthesis of compound 3, whose curved polycyclic skeleton containing three heptagons and two pentagons was identified with X-ray

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• conformational flexibility, allowing them to adopt four key conformations: 1,3-alternate, cone, partial cone, and 1,2-alternate [1][2]. Calix[4]pyrroles are one of the most studied hosts in supramolecular chemistry, finding use in applications of molecular recognition and extraction, drug delivery, ion transport

• calix[4]pyrroles as catalysts may be related to their conformational flexibility, that leads to less preorganized binding and catalytic sites. Calix[4]pyrroles in solution exist in four-different conformations (cone, partial cone, 1,3-alternate, and 1,2-alternate); this macrocyclic flexibility arises

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

• the formation of a coordination bond; the benzene moiety is located in a hydrophobic pocket. bThe conformations of compounds 4a–e are identical, whereas the position of compound 5e (red) is significantly different. Reaction of 2-aminoimidazole (1) with N-substituted maleimides (2) and N

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

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

• halo-divergent strategy from known 1,6-anhydro-2,3-dideoxy-2,3-difluoro-β-ᴅ-mannopyranose. In solution and in the solid-state, all analogues adopt standard 4C1-like conformations despite 1,3-diaxial repulsion between the F2 and the C4 halogen. Moreover, the solid-state conformational analysis of

• order to decipher the key physical properties of complex pyran inter-halides, we performed 19F NMR analysis of halogenated talose analogues 12–15 (Figure 2). First, all analogues adopt standard 4C1-like conformations. Comparison of the vicinal and geminal coupling constants for each organohalogen

• suggests that there is little change in the conformations (although there is an increasing chair distortion for larger halogens, see below). Because F3 is adjacent to the C4 halogen, 19F resonance of F3 occurs at lower field than F2 for analogues 13–15. There is a strong increase in chemical shift of F3

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

• of different and particular structures [7][8]. Additionally, glycans can adopt a wide variety of different shapes; five-membered ring sugars can exhibit envelope and twist conformations usually represented on a pseudo-rotational wheel; while six-membered ring structures can adopt chair (C), boat (B

• ), skew (S), and half-chair (H) conformations (Figure 1). Among them, chair’ shapes typically have the lowest energy and are thus preferred, except few cases in which different conformations can exist in a dynamic equilibrium, as for the iduronic acid that can adopt three low-energy solution conformations

• files of the minimised resulting structures but also files for input to an AMBER simulation (https://glycam.org/). Notably, among the currently available interfaces for modelling oligosaccharide conformations on glycam website, one is dedicated to GAG modelling [51] (https://glycam.org/gag/). 3. CHARMM

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

• subsequently set to 0 kcal/mol leading to the energy diagram in Figure 5. Two TSs leading to each product were found, all four of which utilized a coordinating Cs+ cation. The N1-s-cis and N1-s-trans TSs were the lowest in energy (27.5 kcal/mol and 29.1 kcal/mol, respectively), leading to two conformations of

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

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

• -fluoroalkylamines and the respective cations [6]. Intramolecular hydrogen bonds involving either the carboxy or hydroxy group of 4R- and 4S-hydroxyproline have been identified as key factors in stabilizing the favored conformations in the gas phase. Therein, the contribution of a gauche effect due to electron

• 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

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

• 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

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

• activation energy may allow for oxy-Cope rearrangement at 28 °C. DFT calculations (in toluene) of 5-hydroxyalbireticulene for both the pseudo-axial and pseudo-equatorial conformations of the C5 hydroxy moiety suggest that there is not a significant difference in the free energy barriers for the oxy-Cope

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

• case of compound 2p, unlike the other two compounds, the equilibrium is largely in favor of the product of interest and the NMR spectra confirm this. From the mechanistic point of view of the IMDAF reaction, the presence of both s-cis and s-trans conformations of maleamic acid intermediates in the

Kinetically stabilized 1,3-diarylisobenzofurans and the possibility of preparing large, persistent isoacenofurans with unusually small HOMO–LUMO gaps

• Qian Liu and
• Glen P. Miller

Beilstein J. Org. Chem. 2024, 20, 1099–1110, doi:10.3762/bjoc.20.97

• phenyl substituents, have been synthesized and shown to adopt non-planar conformations with the ortho-alkyl groups located above and below the most reactive 1,3-carbons of the furan ring. These bulky substituents provide a strong measure of kinetic stabilization. Thus, 1,3-dimesitylisobenzofuran and 1,3

• semiconductors. However, such syntheses must account for the projected lack of stability associated with isoacenofurans. We demonstrated that sterically congesting ortho groups on 1,3-diarylisobenzofurans like 3 and 23 force the molecules to adopt non-planar conformations in which the aryl groups rotate out-of

• -plane. The out-of-plane rotations provide for enhanced steric congestion both above and below the most reactive 1,3-carbons of the furan ring, dramatically reducing their reactivity with dienophiles including DMAD, acrylonitrile and singlet oxygen. Due to these non-planar conformations, the HOMO and

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• properties (Figure 4c) [45]. Notably, one tetrahydrofuranoterpenoid 59 is also formed as a major product in the BcBoT2 reaction, despite the low sequence similarity between these sesqui-TSs, which could be explained by similar active-site conformations to stabilize prenyl substrates. Similarly, limonene