Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• partially pre-structuring is seen prior to binding. Although the bound conformation of peptide and glycopeptide is similar, the glycopeptide fluctuates less and resides in specific conformers for more extended periods. This structural analysis which gives a high-level view of the features in the system

• probability distribution gives the best indication of relevant regions. The fourth residue (Thr4) shows multimodal sampling in φ and a bimodal distribution in ψ, with conformers at (−100°, 0°) and (−60°, 130°) being preferred for the antigen (Figure 4E and F). However, when glycosylated the sampling of Thr is

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

• fluorine-containing agrochemicals. Accordingly, this study aims to determine the most likely conformers of some fluorine-containing agrochemicals and to correlate their molecular dipole moments with the respective n-octanol/water partition coefficients (log P), in order to investigate the dependence of the

• conformations along the 1,2-disubstituted ethane motif, the C–C(F) bond was rotated to additionally obtain conformers Igg and Iga, and the corresponding geometries were then optimized. The resulting geometries and relative conformational energies are summarized in Figure 2. At first, we observe that the overall

• geometry is quite similar among the three conformers. Only for Iga, where the gauche fluorine atom points to the opposite direction of the amine group, the triazole ring was farther away from the 1,2-disubstituted ethane moiety. Note that the gas-phase relative conformational energy ΔE increases, i.e

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• spectrum at elevated temperature (e.g., 45, 90, 105 °C) had sharper peaks. This effect of temperature on the spectrum is consistent with restricted dynamics of the backbone such as reputation [30] or slow exchange between different conformers; however, both the trefoil knot and the macrocyclic unknot could

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

• experimental ECD spectra to elucidate the absolute configuration. In the quantum-chemical calculations, the generation of an excessive number of conformers was avoided using a molecular model in which the β-hydroxycarboxylic acid side chain at the C-7 position was simplified to an acetyloxy group (Figure 4A

• conformers were calculated using time-dependent DFT (TDDFT) at the B3LYP/6-311+G(d,p) level of theory. The negative Cotton effect observed at 236 nm in the measured spectrum was in good agreement with that in the calculated ECD spectrum of the (7S,10R,11R)-stereoisomer (Figure 4A). Thus, the absolute

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

• the highest populated conformers are shown in the second column, rendered with VMD (https://www.ks.uiuc.edu/Research/vmd/). A brief summary of the conformational features of each glycoblock and the characteristic linkage or its effect on the (1-6) arm conformation are indicates in the last two columns

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• ]+); this peak persisted at 15, 30, 60 and 120 min time intervals, respectively. Upon the oxidation of 41 two plausible iminium stereoisomers can be formed, Z-42 and E-42, respectively, with each of these iminium stereoisomers existing in two further conformers designated E-42’ and Z-42’. DFT calculations

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• for visualization. An equilibrium likely existed between two conformers where one complex had an additional hydrogen bond and the other included intramolecularly bonded lactate. For the lactate complexes with the larger receptors, whether one dominant conformer or a mixture of two conformers was

• -electron transducer); d) an ion-selective membrane with a plasticized PVC matrix. The inset shows a cross-section of the center of the sensor tip. Studied receptor molecules. MC001 and MC003 lowest energy conformers (COSMO-RS) showing intramolecular bonds. Color coding: white – hydrogen; green – carbon

Three new O-isocrotonyl-3-hydroxybutyric acid congeners produced by a sea anemone-derived marine bacterium of the genus Vibrio

• Dandan Li,
• Enjuro Harunari,
• Tao Zhou,
• Naoya Oku and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1869–1874, doi:10.3762/bjoc.16.154

• major conformers of the PGME amide derivatives between the β,β-substituted carboxylic acids (top) and the α,α-substituted carboxylic acids (bottom), showing an orientational inversion of the PGME groups. NMR data for 1 and 2 in CDCl3. NMR data for 3 and 4 in CDCl3. Supporting Information Supporting

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• experimental 2-CH multiplicity with the one predicted for the pure conformers (Figure 4). As can be seen from the data, both fluoroprolines exhibited stabilization of certain side-chain conformers: the cis-isomer 1 stabilized the C4-endo envelope, whereas the trans-isomer 2 stabilized the C4-exo (Figure 5

• origin of the effect is orbital (the gauche-effect) rather than through space dipolar interaction (assuming that an interaction of dipoles would be attenuated in polar solvents, which was not observed). A stabilization of certain side-chain conformers was also observed in the trifluoromethylated

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

• , indicating the presence of strong hydrogen bonds also in solution. These data suggest that the structures of the predominating conformers should be similar in the solid and liquid phases. Furthermore, we have managed to detect NOE steric proximities between the aldehyde H atom and the H-C(7) (in compounds 3b

• conformer was identified for 23a and two for 23b (Figure 4). In the two preferred conformers of 23b (23b1 and 23b2), the plane of the ortho-formyl-substituted phenyl rings is twisted with 180° compared to each other. The Gibbs free energy difference between the two conformers is 4.1 kJ·mol−1 suggesting the

• interconversion of these conformers is slow in the NMR time-scale. Although the NMR spectra have been measured in CDCl3, we are convinced that the conformations observed in CDCl3 are in good accordance with the ones computed considering the implicit solvent effect of DCM. Based on the structural similarity, the

Five-component, one-pot synthesis of an electroactive rotaxane comprising a bisferrocene macrocycle

• Natalie Lagesse,
• Luca Pisciottani,
• Maxime Douarre,
• Pascale Godard,
• Brice Kauffmann,
• Vicente Martí-Centelles and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2020, 16, 1564–1571, doi:10.3762/bjoc.16.128

• structures (7 and 8) to obtain the most stable conformers (Figure 3) [17][18]. A comparison of the geometries of the most stable conformers indicated that the presence of the template produces a favourable preorganisation of the precursor, not only placing the amino and acid chloride groups in proximity, but

• structure 2025 conformers were examined (see text) and the obtained conformers were ordered by relative energy to obtain the most stable one. (a) Non-functionalized rotaxanes previously described in the literature. (b) The redox-active rotaxane developed in this work. Synthesis of the redox-active rotaxanes

• 1 and macrocycle 2. Most stable conformers obtained by Monte Carlo conformational search using model compounds. (a) Model macrocyclization reaction intermediate in the absence of a template; (b) model macrocyclization reaction intermediate in the presence of a template. 1H NMR spectrum (300 MHz) of

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• 6-31 set with added polarization and diffuse functions [6-31g(d,p)] [21]. B3LYP functional was proven to give accurate description of geometries, frequencies, relative stabilities of different conformers and the energy profile calculation [22]. Implementation of the tools is available at GitHub

• predictions. Employing the Python module [20] and OpenBabel executables [28], the 3D structures of the most stable conformers were generated from the 2D structure of a substrate. Subsequently, structures of all possible palladium intermediates representing both mechanisms (PA and SEAr) were built for each

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• experiments, the relative configuration of compound 21 displaying 3J1,10b = 6.4 Hz was assigned as cis, and the configuration of the compound with 3J1,10b = 6.9 Hz as the trans isomer (Table 1). As it is known, the benzo[a]quinolizidine system can exist as interconvertible conformers due to the presence of a

• should be noted that due to the planar amide fragment the interconversion of the different conformers could be largely suppressed. The X-ray analysis of the above-mentioned (−)-trans-22 [35] and trans-1-ethylbenzo[a]quinolizin-4-ones [40] showed a distortion of the B and C rings, while the substituent at

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

• result was consistent with the observation of a set of ROESY correlations for H-3a/H-5'b, H-5/H-5'b, and H-2''/H-6'' in the most stable conformer of (2S)-isomer 1b, which were all incompatible with any conformers of the (2R)-isomer 1a (Figure 4). Furthermore, the (2S)-configuration was supported by the

• at the mPW1PW91/6-31G+(d,p)-PCM(DMSO) level of theory. The chemical shifts (δcalc) were calculated using tetramethylsilane (TMS) as a reference standard according to δcalc = σ0 − σx, where σx is the Boltzmann-averaged shielding tensor of the most stable 6 conformers within 3.0 kcal/mol and σ0 is the

• shielding tensor of TMS calculated at the same level of theory with σx. For the ECD calculation, single-point energies were recalculated at the M06-2X/6-311+G(d,p) level of theory and solvation effects were included using the PCM solvation model (MeCN) to afford 6 conformers within 3.0 kcal/mol from the

Aryl-substituted acridanes as hosts for TADF-based OLEDs

• Naveen Masimukku,
• Dalius Gudeika,
• Oleksandr Bezvikonnyi,
• Ihor Syvorotka,
• Rasa Keruckiene,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 989–1000, doi:10.3762/bjoc.16.88

• stabilizes the twist conformers stimulating the formation of intermolecular CT states. Consequently, in the PL spectra of neat films of the derivatives the emission band assigned to CT is more prominent. The PL quantum yields of neat films of compound 3, 4, 5, and 6 were found to be 0.03, 0.08, 0.32 and 0.08

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

• an essentially isoenergetic conformer is that found in the X-ray crystal structure. The first conformers where the terminal bispirocyclohexane ring lies axial are significantly higher in energy (ΔG = +1.25 kcal/mol−1 and ΔG = +1.19 kcal/mol−1) than the equatorial conformers as illustrated in Figure 3

• . Notably for both the axial and equatorial conformers, the orientation of the CF2 group, and therefore its dipole, remains perpendicular to the long molecular axis (requirement for +ve dielectric). A similar result was obtained for stereoisomer 11b (see Supporting Information File 1) again with the first

• axial conformer at ΔG = +1.14 kcal/mol−1 above the ground state equatorial conformer. In this case the orientation of the CF2 group, and therefore the dipole, remains perpendicular to the long molecular axis (requirement for −ve dielectric) for both the axial and equatorial conformers. This analysis

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• [44] using conjugate gradient followed by steepest decent. In Sybyl-X multiple conformers of each potential inhibitor compound were created for docking analysis using the prep protocol Docking >1 parameter. Molecular docking of inhibitors in the HDAC8 receptor The inhibitor candidates were docked into

• considering conformers at pH 7 to simulate the physiological conditions where the pH is 7.4. Results were analyzed in both Sybyl-X and UCSF Chimera. Chemical structures of the target diazine-based surrogates for the central core of panobinostat. Docking pose for panobinostat and panobinostat derivatives in

Synthesis of 4-(2-fluorophenyl)-7-methoxycoumarin: experimental and computational evidence for intramolecular and intermolecular C–F···H–C bonds

• Vuyisa Mzozoyana,
• Fanie R. van Heerden and
• Craig Grimmer

Beilstein J. Org. Chem. 2020, 16, 190–199, doi:10.3762/bjoc.16.22

• aromatic triazole foldmers [37]. In their study, using crystallographic and DFT data, they concluded that their folded conformers are held by C–F···H–C hydrogen bonds. To further these studies, we have synthesized a fluorine-containing phenylcoumarin in order to study the fluorine-hydrogen bond. The

• °) are used as examples (Table 1). The theoretical chemical shifts for the carbons appeared to be shifted downfield relative to the experimental carbon peaks (for both stable and unstable conformers) as shown by ‘change’ (Δ = −ve, experimental − theoretical) in Table 1. Comparing the experimental and the

Synthesis and characterization of bis(4-amino-2-bromo-6-methoxy)azobenzene derivatives

• David Martínez-López,
• Amirhossein Babalhavaeji,
• Diego Sampedro and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2019, 15, 3000–3008, doi:10.3762/bjoc.15.296

• the N–N double bond and conformer 3: with a bromine atom in the position of the methoxy group that H-bonded with the azonium proton (see Supporting Information File 1) – were calculated for each compound at 298.15 K. Both alternate conformers were predicted to have higher energies in vacuo (conformer

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• could be ascribed to the greater basicity of the O-ring of the β-anomers [34], which results in a stronger hydrogen bond OH-4⋅⋅⋅O-5. Although stronger interactions were observed for some of the conformers (Table S1, Supporting Information File 1), they corresponded to the less stable conformers

Two new aromatic polyketides from a sponge-derived Fusarium

• Mada Triandala Sibero,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Ocky K. Karna Radjasa,
• Agus Sabdono,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2941–2947, doi:10.3762/bjoc.15.289

• tensor of the most stable 4 conformers within 3.5 kcal/mol and σ0 is the shielding tensor of TMS calculated at the same level of theory with σx. The NMR shifts of structure b was similarly calculated using 50 structures as the OPLS3e-minimized structures and 4 structures as the DFT-optimized structures

A combinatorial approach to improving the performance of azoarene photoswitches

• Joaquin Calbo,
• Aditya R. Thawani,
• Rosina S. L. Gibson,
• Andrew J. P. White and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2019, 15, 2753–2764, doi:10.3762/bjoc.15.266

• paper [18]. Briefly, the different possible pathways for thermal Z–E isomerization were calculated, and each process was weighted by the relative Z-isomer ground state energy and transition state (TS) energy barrier for all possible conformers (see Experimental for details). Focusing first on the 4pzH

• applications. Experimental Computational details. Theoretical calculations were performed using the Gaussian 16 (revision A03) suite of programs [36]. Several rotational conformers of the studied compounds are available due to free rotation of the aromatic rings along single bonds linked to the azo bridge. All

• the possible conformers both in the Z- and E-forms were fully optimized by using the hybrid exchange-correlation PBE0 functional [37] including the Grimme’s dispersion correction in its latest version (D3) [38]. The split-valence Pople’s basis set 6-31G** was used throughout [39]. Transition states

Self-assembled coordination thioether silver(I) macrocyclic complexes for homogeneous catalysis

• Zhen Cao,
• Aline Lacoudre,
• Cybille Rossy and
• Brigitte Bibal

Beilstein J. Org. Chem. 2019, 15, 2465–2472, doi:10.3762/bjoc.15.239

• originate from the presence of several species in solution, such as self-aggregates, mixture of conformers, mixture of diastereoisomers or complexes with different stoichiometry. To investigate the possible self-aggregation of complexes 1a–c (7 mM), VT NMR experiments were conducted between –30 °C and 60 °C

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

• conformations. This will add an entropy penalty for the E-isomers. Interatomic distances from NOE buildup rates Interatomic distances, derived from NOE buildup rates, are summarized in Figure 7. Signal overlap prevented an analysis accounting for the presence of an ensemble of conformers such as NAMFIS [39][40

• ]. For example, each CH2 signal is generated by four CH2 protons which are chemically equivalent in the averaged chemical structure (≈ the 2D molecular structure) but not in individual conformers. They cannot be distinguished on the NMR timescale. Therefore, the calculated distances rave, being averages

• with contributions from all conformers, are biased for shorter distances, i.e., rave = ⟨1/r6⟩ instead of rave = 1/⟨r6⟩ [41]. However, they still should allow a comparison between the different compounds (Z)-1a–d. Thus, increased conformational flexibility is indicated by increasing distances from (Z

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• temperature. Computational details: All calculations were carried out using the TURBOMOLE version 7.2 quantum chemistry package [67]. Geometry optimizations of all compounds in different conformers were carried out using DFT with PBE approximation to the exchange-correlation (XC) functional and employing the

• calculations for two conformers (A and B) of each double bond isomer ((E)-2b and (Z)-2b), photocyclization and oxidation products 8a and 8b are given. Supporting Information File 302: Experimental procedures, analytical data and quantum chemical calulations. Acknowledgements The Jung group thanks the Deutsche