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

• the solution structures yields 5 clusters for the antigen and 4 clusters for the Tn-antigen (Figure 5A and B). The predominant conformer in both antigens is the extended form (Figure 5C), while for the Tn-antigen, the fourth cluster exhibits a more compact conformation (a transparent green conformer

• in Figure 5C) as noted in previous analysis. A cluster analysis of the bound antigens yields 5 clusters for the antigen and 4 clusters for the Tn-antigen (Figure 5D and E). The predominant conformer in both antigens is similar (Figure 5F), as noted in previous analysis. For the antigen, the first

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

• level of theory, ωB97X-D/6-311++G(d,p) [16][18], resulting in conformer Iag (Figure 2). This conformer has one fluorine atom in an anti-orientation and the other one in a gauche-orientation relative to the vicinal oxygen atom (pointing towards the amine hydrogen atom). To evaluate the other possible

• polar solvent (e.g. water), however, decreases the difference in energy among conformers and Igg becomes the most stable conformer in solution, i.e., a double gauche effect takes place (see data in parentheses in Figure 2). This is not surprising, since Igg has the highest dipole moment (data shown in

• conformational stabilities, we performed a numerical experiment in which the C–C(F) bond is rotated from conformer Iag keeping other geometrical parameters fixed. In this way, we can specifically investigate the intramolecular interactions governing conformational preferences in the 1,2–disubstituted ethane

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

• modification, we have considered two biantennary systems, one terminating with β(1-2)-GlcNAc on both arms (ngf) and the other with terminal β(1-3)-Gal on both arms (gf), shown in Figure 1. In both glycoforms core α(1-3)-Fuc occupies a stable position, with one single conformer populated (100%), see Tables S1

• -3) arm is much more rigid relative to non-xylosylated species, see Table S3 in Supporting Information File 1, losing its “two conformer” dynamics characteristic of the biantennary mammalian N-glycans [24], also retained in the plant N-glycans with only α(1-3)-Fuc discussed above, see also Tables S1

• is able to form when in a 1C4 chair with the α(1-6)-Man, which may compensate for the steric compression, making the 1C4 chair the highest populated conformer at 76% within an N-glycan scaffold. Both experimental and ab-initio theoretical studies [36][37][38] have shown that the 1C4 chair is

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

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

• for the major amide rotamer in water, where the conformer was less defined. Overall, these outcomes demonstrate that the CF3 group favors an equatorial placement, but the preference is notably weaker as compared to the monofluoroprolines (Figure 5). It could be speculated that if the dipolar

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

• 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

• possibility of a rotation of the ortho-formylphenyl group. Notably, conformer 23b1 is the more stable one, corresponding to the structure determined by solid-phase X-ray measurements (Figure 3, right). It should be mentioned that a few signals in the NMR spectra of 23b, e.g., δHC−N (5.71 dd), δHC= (131.1

• energy conformer of stereoisomer 23a and those of two minimal energy conformers of 23b (23b1 and 23b2) in DCM solution, based on DFT calculations. Rearrangement of methylenedioxy-substituted aminoaldehyde 1a to regioisomer 2a and formation of the dimer-like product 3a. Synthesis of 1-arylisoindoles 6 and

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

• conformer. A quick geometry optimization (maximum number of iteration steps was set to 5) was then applied to refine the intermediates and discard the ones with high energy (energy cut off of 10 kcal·mol−1). Full geometry optimisation followed by the frequency and thermochemistry analysis was then performed

• initial guess due to particularly bad initial geometry – discard the conformer/intermediate, (iv) decomposed intermediate (no Pd–C bond determined by interatomic distance analysis) – discard intermediate. Literature validation In order to test the developed algorithm, a representative literature data

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• with the Gaussian software [26]. Firstly, the equilibrium conformer search at the ground state was performed by using the MMFF (molecular mechanics force fields) method, and this geometry was used for further optimization. The vertical singlet and triplet energy values were calculated by using the

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

• structures 1a and 1b The conformational search on structure 1a began by applying 100,000 steps of the Monte-Carlo Multiple Minimum (MCMM) method with PRCG energy minimization using the OPLS3e force field (gas phase) to obtain 20 conformational isomers within 5.0 kcal/mol from the minimum energy conformer

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

• difluorocarbene addition to alpha-fluorostyrenes [13]. This used the extraordinary useful method for the generation of difluorocarbene from the Ruppert–Prakash (TMSCF3) reagent [14]. DFT analysis suggests the lowest energy conformer of aryl α,β,β-trifluorocyclopropane 7 orients the C–F bond perpendicular to the

• properties significantly, however, we were interested in assessing the energy required for the bispirocyclohexane ring to adopt an axial rather than the lower energy equatorial arrangement. For 11a, the lowest energy conformer found was a rotamer around the central C–C bond linking the cyclohexane rings, but

• 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

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• performed using SPARTAN Version 5.11. Conformational searches of 36 were carried out using Monte Carlo method within MMFF94 force field, and the AM1 semiempirical method [72] was used to optimize the global minimum conformer. The geometry of the most abundant minimum energy conformer was successively

• . Once the lowest energy conformer was calculated, the three principal moments of inertia (Ixx, Iyy, Izz) and normalized principal moments of inertia, npr1 (Ixx/Izz) and npr2 (Iyy/Izz) were determined and plotted on a triangular graph with the vertices (0,1), (0.5,0.5) and (1,1) representing a perfect

• rod, disc and sphere, respectively. Chemical structure of representative approved drugs containing a spirocyclic moiety. Top: Selected NOE contacts from NOESY 1D spectra of compound 36; bottom: low energy conformer of 36, Z rotamer, using ab initio calculation at the HF/3-21G* level. PCA plot

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

• Gaussian 09W (Rev C.01) at the B3LYP/6-311G level. Geometry optimization and calculation of NMR parameters for TMS and CCl3F at the same level provided reference chemical shifts for 1H, 13C, and 19F. The chemical shifts for the lowest energy structure (Φ = 65.3°) and the most unstable conformer (Φ = 5

• calculated 13C NMR chemical shifts for both the optimized and least-stable DFT-generated conformations, the RMSD values were found to be 8.84 ppm and 8.79 ppm, respectively. The RMSD value for the calculated 1H NMR chemical shifts of the optimized conformer was found to be substantially smaller (RMSD = 0.14

• ppm) than that for the least-stable conformer (RMSD = 0.57 ppm). The theoretical coupling constants at the same 24 geometries from geometry scan for coumarin 6 were obtained using the same functional and level of theory (B3LYP/6-311G). The coupling constants (F···C or F···H) for selected nuclei of

Synthesis, liquid crystalline behaviour and structure–property relationships of 1,3-bis(5-substituted-1,3,4-oxadiazol-2-yl)benzenes

• Afef Mabrouki,
• Malek Fouzai,
• Armand Soldera,
• Abdelkader Kriaa and
• Ahmed Hedhli

Beilstein J. Org. Chem. 2020, 16, 149–158, doi:10.3762/bjoc.16.17

• cycle at 126 °C for compound 4b. Typical diffractogram observed for compound 2b at 398 K. Typical diffractogram observed for compound 4a at 411 K. Conformer of lowest energy of compounds: 4c, conformation A, (a) front view, (a’) top view, (a”) side view; 4b, conformation B, (b) front view, (b’) top view

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

• performed for any of the species, the following calculations were performed: To ensure that the conformation shown in Figure 2 was the thermodynamically most stable arrangement around the azo moiety, free energies for two alternative arrangements – conformer 2: with both bromine atoms on the same side of

• 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

• 2: 1.1 kJ/mol for the 6-membered ring and 2.2 kJ/mol for the 5-membered ring; conformer 3: 20 kJ/mol for the 6-membered ring and 19 kJ/mol for the 5-membered ring). Thus, conformer 2 was slightly higher in energy than conformer 1 and should be populated at room temperature. However, we did not carry

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

• (Figure 2). After a full conformational search with MM3, the lower-energy structures were submitted to optimization with B3LYP/6-311+G**, and then, single-point calculations with M06-2X/6-311+G** (Figure S1 and Table S1, Supporting Information File 1). After calculations for each low-energy conformer and

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

• Soleiman E. Helaly,
• Wilawan Kuephadungphan,
• Patima Phainuphong,
• Mahmoud A. A. Ibrahim,
• Kanoksri Tasanathai,
• Suchada Mongkolsamrit,
• Janet Jennifer Luangsa-ard,
• Souwalak Phongpaichit,
• Vatcharin Rukachaisirikul and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293

• File 1. ECD theoretical calculations TDDFT-ECD was used to perform theoretical ECD calculations. Conformational searches for the investigated compounds were first performed with a MMFF94S force field and an energy window of 10 kcal/mol using Omega2 software [54][55]. Each resulting conformer was then

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

• conformational isomers within 35 kcal/mol from the minimum energy conformer. The next optimizations were performed at the M06-2X/6-31G(d) level of theory and solvation effects were included using the PCM solvation model (DMSO). Frequency calculations were carried out at the same level of theory to confirm the

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• quaterphenyls are unavailable in the literature but these values and other estimates for relative energies can be predicted by theory. Starting with the lowest energy conformer for each quaterphenyl, we first computed heats of formation using the T1 method [39]. Predicted values (Supporting Information File 1

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

• calculated in MacroModel 9.9 with the OPLS3e force field, CHCl3 as solvent and dielectric constant 9.1 [48][49]. Redundant conformer elimination in MacroModel was used to reduce the number of conformations to 10–20 structures [50]. Synthesis Synthesis of 6-methoxyindan-1-one (3) Compound 2 (2.523 g, 14.0

• reaction (Figure S47, Supporting Information File 1). The differences in ring strain between the E- and Z-isomers show an exponential correlation to the linker length. Conformer ensembles for the macrocyclic stiff stilbene diethers 1a–d. Dihedral angles between the two aromatic rings are given in

Synthesis and anion binding properties of phthalimide-containing corona[6]arenes

• Meng-Di Gu,
• Yao Lu and
• Mei-Xiang Wang

Beilstein J. Org. Chem. 2019, 15, 1976–1983, doi:10.3762/bjoc.15.193

• ]. The observation of the single set of proton and carbon resonance signals of 3 indicated the presence of the conformer with high symmetry or most likely a mixture of conformers which underwent very fast interconversion relative to the NMR time scale. In comparison to diethyl terephthalate, a

Synthesis, enantioseparation and photophysical properties of planar-chiral pillar[5]arene derivatives bearing fluorophore fragments

• Guojuan Li,
• Chunying Fan,
• Guo Cheng,
• Wanhua Wu and
• Cheng Yang

Beilstein J. Org. Chem. 2019, 15, 1601–1611, doi:10.3762/bjoc.15.164

• dichroism (CD) spectroscopy. The first fraction showing negative CD signals was assigned to the Sp conformer and the second fraction showing positive CD signals was assigned to the Rp conformer. Aggregation behaviors of the enantiopure chiral pillar[5]arene derivatives were investigated by adding water into

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• determined, no predominant conformer was found. As shown in Figure 3A and B both tripeptides indicate a fully flexible conformation. Corzana et al. suggested for the C- and N-protected, glycosylated ʟ-serine residue an extended conformation without intramolecular hydrogen bond between the amide proton of

2,3-Dibutoxynaphthalene-based tetralactam macrocycles for recognizing precious metal chloride complexes

• Li-Li Wang,
• Yi-Kuan Tu,
• Huan Yao and
• Wei Jiang

Beilstein J. Org. Chem. 2019, 15, 1460–1467, doi:10.3762/bjoc.15.146

• suggests that the conformational interconversion is slow at this temperature and only one conformer is predominant in the solution at 298 K. However, the exact conformer cannot be assigned because the two conformers have the same number of peaks. In contrast, H3 of 2 are broadened even at room temperature

• between the amide NH protons and the pyridine nitrogen atoms in 2, which pre-organizes the cavity for molecular recognition. How would this affect the binding affinity of 2? To answer this question, molecular modelling was performed. Only conformer I of 1 was used for the molecular modelling but both

Efficient resolution of racemic crown-shaped cyclotriveratrylene derivatives and isolation and characterization of the intermediate saddle isomer

• Sven Götz,
• Andreas Schneider and
• Arne Lützen

Beilstein J. Org. Chem. 2019, 15, 1339–1346, doi:10.3762/bjoc.15.133

• these studies an intermediate saddle conformer could also be isolated and characterized by 1H and 13C NMR spectroscopy. The HPLC separation method was further developed in order to allow investigations on the racemization behavior of the cyclotriveratrylene derivative. Keywords: chiral resolution

• the intermediate saddle conformer. Results and Discussion Synthesis and chiral resolution of 1 and isolation of the saddle isomer The synthesis of (rac)-1 was accomplished according to the already mentioned protocol by Rousseau and co-workers (Scheme 3) [60] although it should be noted here that

• corresponds to the saddle conformer and is marked with 1-S. a) 1H NMR spectrum of the neat crown isomers of (rac)-1 in CD3OD (400 MHz, 298 K); b) 1H NMR spectrum in CD3OD (400 MHz, 298 K) of a sample of (rac)-1 after heating it to 200 °C in DMSO and quenching the solution by pouring it into an ice water

Bambusuril analogs based on alternating glycoluril and xylylene units

• Tomáš Lízal and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2019, 15, 1268–1274, doi:10.3762/bjoc.15.124

• CD3CN showed two sets of signals (Figure 3) which were assigned to the calculated conformers. Conformer 1a-1 possesses a plane of symmetry, therefore, is characterized by single signals of methyl (H6), methine (H5) and aromatic (H1 and H3) protons. Contrary, 1a-2 is characterized by two signals for each

• in favor of 1a-1 which remained constant at even lower temperature. By application of the Boltzmann distribution to the conformer population, we have calculated that 1a-1 is more stable by 0.13 kcal mol−1 than 1a-2. Conformer 1a-1 is preferred probably due to its higher symmetry. Diastereomer 1b was

• reflecting the presence of conformers 1b-2 and 1b-1. However, the ratio of these conformers is 82:1 in favor of 1b-1 which translates to the energy difference of 2.04 kcal mol−1. Stabilization of the 1b-1 conformer can be attributed to the intramolecular hydrogen bonding interaction between the oxygen atom