C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• substrates in their void. Keywords: C–C coupling; conformational analysis; nonplanar porphyrin; Pd-catalysis; porphyrin; Introduction Porphyrins are tetrapyrrolic macrocycles that perform essential processes in nature, such as oxygen transport in hemoglobin and photosynthesis [1]. Porphyrins are often

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

• -tetrahalohexanediols. Conformational analysis and lipophilicities of the latter compounds were determined and trihalogenated alkanes were incorporated into piperidines of pitolisant [23]. This work was an extension of our synthetic routes to multivicinal organofluorines to unveil some of their unique properties [24

• ) [24]. The solution and the solid-state conformational analysis were supplemented with DFT calculations to understand key conformational drivers. This study adds more data to the field of nuclear magnetic resonance (NMR) spectroscopy of polyhalogenated molecules. It should be noted that the NMR

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

• , especially in bacterial glycans, makes the structural and conformational analysis of glycans extremely difficult, posing a considerable challenge when employing conventional structural biology methods for glycan analysis [10][12]. Nevertheless, understanding the three-dimensional structure of glycans is

• , modifications can sometimes be required and can be achieved through ab initio calculations or programs like for example VFFDT [71]. Tools for the conformational analysis of glycans in the free state The structure and biological functions of glycans are closely intertwined; the roles they play are influenced not

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• , conformational analysis performed by variable temperature NMR led to the conclusion that the open and closed conformations have similar energies and are in fast exchange at ambient temperature. This fluxionality resulted in a relatively low affinity for the electron-poor aromatic guest 2,4,7-trinitro-9

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

• . The resulting spirocyclic compounds are formed with a clear preference to the syn diastereomer over anti which can be rationalized by conformational analysis of the Claisen rearrangement precursors to their formation. Examples of approved spirocyclic drugs. (a) Earlier reported Rh(II)-catalyzed

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

• acyclic conformational analysis. Three divergent mechanistic pathways can be formulated by considering the different conformers of protonated imine 7, namely iminium ions 12a–c (Scheme 3). In each case, the chair-like transition state of the intramolecular aza-Prins reaction is controlled by the C7

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• Maxime Pypec Laurent Jouffret Claude Taillefumier Olivier Roy Université Clermont Auvergne, Clermont Auvergne INP, CNRS, ICCF, F-63000 Clermont–Ferrand, France 10.3762/bjoc.18.85 Abstract The synthesis and conformational analysis of the first series of peptoid oligomers composed of consecutive N

• ]. Conformational analysis and self-assembling properties The 1H NMR analysis of monomer 1 in various solvents including CDCl3, CD3CN, C6D6, CD3OD, D2O, and DMSO-d6 showed two sets of resonances in proportions varying from 75:25 to 90:10 (Table 3). These two sets of signals were characterized as the backbone cis

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• energetically more stable, by 5.0 kcal mol−1 in methanol and by 3.7 kcal mol−1 in dichloromethane, than lactone 20. The computations were in good agreement with the experimental results (Figure 3 and Figure 4). To explain why lactone 10 is formed, a conformational analysis for the epoxide 7 was performed. It is

• seen that the conformation is quite appropriate for the formation of lactone 10. The hydrogen bond between the C=O group of methoxy ester and NH group of the carbamate in 7 provides an appropriate conformation for the formation of lactone 10. Additionally, according to the conformational analysis of

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• macrocycle and of the Lys–His bond, which is part of the cross-link, is prevented by the stapling (Figure 3 and Supporting Information File 1, Figures S8 to S10). Conformational analysis The identification of two isomers of P5 by LC–MS led us investigate the possibility of diastereomers and conformers in the

• . Time-averaged analysis was performed on the ensemble of structures obtained from the last 500 ns of each simulation run (i.e., a cumulative total of 7.5 μs per peptide; see Supporting Information File 1 for further methodological details and extended analysis). Figure 4 summarises the conformational

• analysis on the macrocycle in the cis and trans isomer form of P5. PCA reveals that the first three principal components (PCs) respectively capture 39.0, 21.3, and 13.4% of the total variance in P5 cis, and 31.2, 25.4, and 9.9% in P5 trans. PCA-based clustering with a minimum distance of 4.0 Å in the three

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• results of its corresponding nickel(II) [18] and palladium(II) [19][20] complexes with the analogous tests obtained in the case of having a benzylic substituent at the same position. Also, DFT calculations are run in order to study the conformational analysis of the synthetized complexes. Results and

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• has been a topic of strong interest over the past decades. With this in mind we have characterized a series of direct meso-halogenated porphyrins using single crystal X-ray crystallography. This is accompanied by a detailed conformational analysis of all deposited meso-halogenated porphyrins in the

• . Additionally, we have used density functional theory calculations to determine the structure of several halogenated porphyrins. This contrasts conformational analysis with existing X-ray structures and gives a method to characterize samples that are difficult to crystallize. By using the methods outlined above

• need of crystallization, using DFT calculations with a high degree of accuracy. Keywords: conformational analysis; crystal engineering; halogenation; macrocycles; porphyrins; Introduction Crystal engineering using porphyrins as a scaffolding unit has been a topic of increasing interest over the past

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• important NOESY correlation observed for 10* is also shown in Scheme 4. The conformational analysis of the (2S)-isomer carried out by CONFLEX (MMFF94S), however, was not very encouraging since the four contiguous single bonds between the heterotricycle and the menthyl group were found to be freely rotating

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• nucleic acids [89]. Following early advances by Micura and co-workers in the late 2000s that investigated the suitability of 19F NMR for the conformational analysis of single and double helix RNA strands [90][91][92][93] 19F NMR has found a particularly rich niche of applications in the conformational

• analysis of higher-ordered DNA and RNA G-quadruplex structures. G-quadruplexes are four-stranded nucleic acid secondary structures formed in specific guanine-rich sequences showing, in general, highly polymorphic structures and various folding topologies. These structures have been suggested to play an

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• have led to promising applications of helicenes. The latter have been studied with respect to conductivity [12][13][14][15], nonlinear optics [16][17], circularly polarized luminescence [18][19][20][21][22][23][24], organocatalysis [25][26][27][28][29], conformational analysis [30], chirality sensing

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• for E-alkenes in medicinal chemistry. Keywords: Alzheimer's disease; bioisostere; conformational analysis; gauche effect; stereoselective synthesis; Introduction Piperine (1, Figure 1) is a well-known natural product that is derived from peppercorns [1][2][3]. Many biological studies of 1 have been

• compound 2, the conformational analysis of this molecule by NMR and molecular modelling studies, a comparison of the photostabilities of parent compound 1 vs derivative 2, and a comparison of the inhibitory activities of 1 vs 2 towards both AChE and BACE-1. Results and Discussion Synthesis Jacobsen and co

• that the two peaks correspond to the two enantiomers of 2 and, if that assumption is true, then the optical purity of this sample is 98% ee. Conformational analysis Having completed the synthesis of the target molecule 2, the next task was to investigate the conformational behavior of this molecule

Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction

• Daniela Rodrigues Silva,
• Joyce K. Daré and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2020, 16, 2469–2476, doi:10.3762/bjoc.16.200

• on conformation, membrane permeation, pharmacokinetic properties, among other parameters [7]. From a conformational analysis point of view, the fluorine atom presents minimal steric effects; on the other hand, due to its high electronegativity, the C–F bond is highly polarized, which characterizes it

• organic molecule, as above mentioned. Therefore, this work also seeks to assess a correlation between calculated μ values and experimental log P measures, in order to unveil the dependence of lipophilicity with molecular conformation. Results and Discussion Conformational analysis of penoxsulam Given the

• high degree of freedom in the chemical structure of penoxsulam (I), the conformational analysis started with a Monte Carlo conformational search at the ωB97X-D/6-31G(d,p) [16][17] level of the density functional theory (DFT). The global energy minimum conformation was then re-optimized in a higher

Lipophilicity trends upon fluorination of isopropyl, cyclopropyl and 3-oxetanyl groups

• Benjamin Jeffries,
• Zhong Wang,
• Robert I. Troup,
• Anaïs Goupille,
• Jean-Yves Le Questel,
• Charlene Fallan,
• James S. Scott,
• Elisabetta Chiarparin,
• Jérôme Graton and
• Bruno Linclau

Beilstein J. Org. Chem. 2020, 16, 2141–2150, doi:10.3762/bjoc.16.182

• meaningless. This was a surprise, as series D and E are relatively rigid, which simplifies conformational analysis. The remarkably similar DFT-logP values suggest that the influence of the fluorination is underrepresented in the calculations. The following observations are noteworthy. The trifluorinated D5

Muyocopronones A and B: azaphilones from the endophytic fungus Muyocopron laterale

• Ken-ichi Nakashima,
• Junko Tomida,
• Tomoe Tsuboi,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 2100–2107, doi:10.3762/bjoc.16.177

• ) [25]. After conformational analysis, geometry optimization was performed for two possible stereoisomers with the (7S,10R,11R)- and (7S,10S,11S)-configurations using density functional theory (DFT) at the CAM-B3LYP/6-311+G(d,p) level of theory. In addition, the ECD spectra of the DFT-optimized

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• (https://www.ks.uiuc.edu/Research/vmd/) and the graphical statistical analysis with RStudio (https://www.rstudio.com). Conformational analysis of the (1-6) arm in four hybrid N-glycoforms, β(1-2)-xylosylated A2G2 (top-left), β(1-2)-xylosylated FA2G2 (bottom-left), β(1-2)-xylosylated α(1-3)-core

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• (Supporting Information File 1, page S45) and used for the figures of the paper. The conformations of the reported structures have been determined by conformational analysis. The solution-phase Gibbs free energies were obtained by frequency calculations as well. The G values obtained were given under standard

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• C2''. As positive ΔδS−R values were obtained for 10''-NH and H-11'', and negative values for 2''-NH, H-2', H-3', H-4', H-5', and 2-NH (Figure 3), an (S)-configuration was assigned to C-2''. The chirality of the AcTyr residue was investigated by computer-assisted conformational analysis and NMR

Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes

• Zeguo Fang,
• Nawaf Al-Maharik,
• Peer Kirsch,
• Matthias Bremer,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2020, 16, 674–680, doi:10.3762/bjoc.16.65

• conformational analysis of 11a (and 11b) was conducted computationally (ωB97X-D/6-311+G(2d,p)//ωB97X-D/6-31G(d) + ZPE level (see Supporting Information File 1)). There are many potential low energy conformations arising from alkyl side chain C–C bond rotations which would not be anticipated to change the overall

Anion-driven encapsulation of cationic guests inside pyridine[4]arene dimers

• Anniina Kiesilä,
• Jani O. Moilanen,
• Anneli Kruve,
• Christoph A. Schalley,
• Perdita Barran and
• Elina Kalenius

Beilstein J. Org. Chem. 2019, 15, 2486–2492, doi:10.3762/bjoc.15.241

• ) without (PBE0/def2-TZVP) and with (PBE0-D3/def2-TZVP) dispersion correction because in the gas phase dispersion plays an important role in the formation of supramolecular complexes [24][25][26][27][28][29][30]. Conformational analysis was first performed for both tautomers of the monomer to ensure that

• further calculations were carried out for the most stable tautomer. The conformational analysis revealed that the pyridone tautomer (1) is ≈150 kJ/mol lower in energy than the dihydroxy tautomer (1OH). The geometry optimizations showed that the geometry of [12 + Me4Nendo]+ is similar without and with

Effect of ring size on photoisomerization properties of stiff stilbene macrocycles

• Sandra Olsson,
• Óscar Benito Pérez,
• Magnus Blom and
• Adolf Gogoll

Beilstein J. Org. Chem. 2019, 15, 2408–2418, doi:10.3762/bjoc.15.233

• ) the ring strains of the E- and Z-isomers are similar. The differences in ring strain between the E- and Z-isomers show an exponential correlation to the linker length (Figure 5). Conformational analysis To obtain further information regarding the reason for the observed photoisomerization properties

• of the macrocyclic stiff stilbene diethers, a conformational analysis was undertaken (Figure 6). According to X-ray crystallography, in compound (E)-7 (Scheme 4) the aromatic rings of the two indane units are in the same plane (dihedral angle 180°), whereas in (Z)-7 this angle is 9.1° [21]. In the

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• ’ = ΔA/c × d, where c is the molar concentration of the chiral ligand, assuming 100% complexation (A = absorption; d = path length of the cell). Δε’ is expressed in [M−1 cm−1] units. Conformational analysis and ECD calculations The conformational search was performed with ComputeVOA [35] using the MMFF94