Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• various force fields dedicated for carbohydrates. The accurately predicted oligosaccharide conformations are good starting points for further investigations. Of particular interest are the evaluations of the dynamics of glycans and their interactions with proteins which is a most significant concern in

• and the available utilities (codes) helps with the general problems in sampling, scoring, and nomenclature related to glycan modelling. It samples glycosidic bonds, ring forms, side-chain conformations, and utilises a glycan-specific term within its scoring function. The tool also consists of

• -builder.cermav.cnrs.fr/) with an interactive and more usable interface (Figure 10). The software translates a glycan sequence or polysaccharide repeat unit into the coordinate set of the corresponding tertiary structure, in one or several of its low energy conformations. The construction follows an intuitive scheme

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

• Information File 470: Conformations of host 1, TLC knot-forming scheme, experimental procedures and copies of 1H NMR spectra. Acknowledgements We thank Beth Buckwalter for the acquisition of the NMR spectra and Lisa Mertzman for her valuable assistance. We gratefully acknowledge helpful discussions with

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

• -fluoropropanol) [22], while for the higher alkanols, β-fluorination leads to more lipophilic compounds than γ-fluorination [28]. The higher logP of β-fluorinated alcohols has been explained both by the occurrence of conformations with opposing dipole moments of the C–F and C–O bonds, as well as the reduction of

• relates to the difference in Gibbs energy of the free ligand conformations of this solute in the respective solvents. Quantum chemistry calculations of Gibbs energies in octanol and water thus provide theoretical estimations of lipophilicities. Such estimations require systematic conformational analyses

• and geometry optimizations. Ho and co-worker showed that the use of the lowest-energy conformations as calculated in the respective solvents gave more accurate lipophilicities than the use of the lowest energy conformations in the gas phase [36]. Somewhat surprisingly, implicit solvent models proved

Isolation and structure determination of a tetrameric sulfonyl dilithio methandiide in solution based on crystal structure analysis and ⁶Li/¹³C NMR spectroscopic data

• Jürgen Vollhardt,
• Hans Jörg Lindner and
• Hans-Joachim Gais

Beilstein J. Org. Chem. 2020, 16, 2057–2063, doi:10.3762/bjoc.16.172

• , electrostatic interaction with and charge polarization by the positively charged sulfur atom [56] and silicon atom [57], and negative nC–σ*SPh hyperconjugation [56][58]. The anions of (2a)4·(THF)6 and (2a)6·Li2O·(THF)6 adopt conformations around the carbon sulfur bond, which would allow for stabilization by

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

• , namely the three gg, gt and tg conformations for each 1-6 torsion. The topology file for each structure was obtained using tleap [31], with parameters from the GLYCAM06-j1 [32] for the carbohydrate atoms and with TIP3P for water molecules [33]. All calculations were run with the AMBER18 software package

• cpptraj [31] and visually analysed with the Visual Molecular Dynamics (VMD) software package [34]. Root mean square deviation (RMSD) and torsion angles values were measured using VMD. A density-based clustering method was used to calculate the populations of occupied conformations for each torsion angle

• the central xylose. As outcomes of the complex interaction the branched arms can establish, the equilibrium of the (1-6) arm is restrained in conformations previously not significantly populated, see Figure 4 and Supporting Information File 1, Table S7, and the GlcNAc-β(1-2)-Man linkage in both arms

pH- and concentration-dependent supramolecular self-assembly of a naturally occurring octapeptide

• Goutam Ghosh and
• Gustavo Fernández

Beilstein J. Org. Chem. 2020, 16, 2017–2025, doi:10.3762/bjoc.16.168

• 24 h, which suggested the formation of very stable conformations under the investigated conditions. Although the mechanism of transformation is not clear to us at this stage, we hypothesize that multiple intermolecular interactions may play an important role in the transformation. At high

• concentrations, peptide molecules can come into closer contact and experience strong intermolecular attractive forces to facilitate the β-sheet formation, whereas a low concentration may preferentially favor coiled or helical conformations by salt bridges between positively charged (Arg+) and negatively charged

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

• dipoles do not sufficiently interact in this situation. However, minor conformations with axial CF3 substituents do exist in the model compounds 3 and 4 (Figure 7). For example, both species were quite well separable using standard silica gel chromatography settings, where 4 appeared less polar than 3

• . The existence of the minor conformations will also be relevant in the explanation of the amide-rotation barriers (vide infra). It should be noted that calculation of the net dipole is of little aid when accessing polarity of the model compounds 1–4 [77]. For example, the dipole moment calculated for

• influence onto the trans/cis ratio. In contrast, the gauche-effect in fluoroprolines causes a much stronger stabilization of the C4-conformations, as this propagates into stronger effects in the trans/cis equilibrium. In addition, there is a weak but systematic modulation in the trans/cis equilibrium caused

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• 3D ball-and-sticks model only represents one of several possible conformations of clozapine but that all these conformations are inherent in the 2D-line structure. The dichotomy, really that between fundamental quantum chemistry and the common bonding models, which is made evident in Figure 1 and

• : Quantum mechanical calculations require 3D molecular structures, which each only represent one of sometimes very many energetically accessible conformations for flexible molecules. Thus, the calculations must be preceded by extensive conformational searches and many conformations must be stored for each

• molecule. The seemingly less sophisticated 2D models are the answer because they consider all conformations implicitly. For instance, the 2D Gasteiger–Marsili charge model [38][39] could be extended to produce fast, approximate 2D representations of electron densities that give extrema of the molecular

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

• 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

• (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

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• inversion of the local electronic environment, or the precise deletion of hydrogen-bond donors, respectively, with minimal steric variation [7]. The latter aspect is a crucial determinant in enabling fluorinated materials to adopt intriguing conformations which are a manifest representation of stabilising

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• that steric hindrance plays a role during the reaction. Oxazolones 2a–j contain two exocyclic C=C bonds in their skeleton and these can, in principle, have different conformations. The NMR characterization of 2a–j showed that they are obtained as single isomers. The oxazolone exocyclic C=C bond has the

Bipyrrole boomerangs via Pd-mediated tandem cyclization–oxygenation. Controlling reaction selectivity and electronic properties

• Liliia Moshniaha,
• Marika Żyła-Karwowska,
• Joanna Cybińska,
• Piotr J. Chmielewski,
• Ludovic Favereau and
• Marcin Stępień

Beilstein J. Org. Chem. 2020, 16, 895–903, doi:10.3762/bjoc.16.81

• , and θ, the torsion angle between the two monopyrrole axes (Supporting Information File 1, Table S1). In contrast to the previously reported cR1O dilactams, which were nearly planar [32], systems with n = 2 and 3 are characterized by a twisting distortion, which produces helicene-like conformations

Aldehydes as powerful initiators for photochemical transformations

• Maria A. Theodoropoulou,
• Nikolaos F. Nikitas and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2020, 16, 833–857, doi:10.3762/bjoc.16.76

• biradical intermediate may lead to all four conformations. Photolysis products of benzaldehyde (8) in different solvents. a) In benzene or ethanol. b) In hex-1-yne. N-tert-Butylbenzamide formation proceeds via a benzoyl radical. Photochemical pinacol coupling. Photochemical ATRA catalyzed by 4-anisaldehyde

Towards triptycene functionalization and triptycene-linked porphyrin arrays

• Gemma M. Locke,
• Keith J. Flanagan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2020, 16, 763–777, doi:10.3762/bjoc.16.70

• the two porphyrin units resulting in very strong electronic coupling, i.e., losing the characteristic of individual units due to delocalization of π-electrons. The Soret bands of the four different conformations of the porphyrins in the butadiyne-linked dimer 20 are barely distinguishable from one

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

• adopt conformations with low overall molecular polarities. A comparison of the Δε for 8 and 9 illustrates that incorporation of the third alpha-fluorine lowers the overall Δε value. This is presumably due to a resulting decrease in the overall molecular dipole moment () along the minor axis. When an

• 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

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• aspects of compounds 11 and 12 The ground state structures (S0) for both molecules 12 and 11 in their Z-conformations are similar (Figure S-8.1A and B, Supporting Information File 1) with the length of the N–O bond varying between r(N–O) = 1.423 (12) and 1.425 Å (11). (Table S-8.1, Supporting Information

Synthesis and circularly polarized luminescence properties of BINOL-derived bisbenzofuro[2,3-b:3’,2’-e]pyridines (BBZFPys)

• Ryo Takishima,
• Yuji Nishii,
• Tomoaki Hinoue,
• Yoshitane Imai and
• Masahiro Miura

Beilstein J. Org. Chem. 2020, 16, 325–336, doi:10.3762/bjoc.16.32

• numerous attempts for obtaining crystals suitable for the X-ray analysis. Based on these observations, it is reasonable to conclude that the tert-butyl substituents effectively restricted the stacking structure to the specific conformations, thereby facilitating the assembly of well-ordered aggregates 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

• crystal structure and solution-state NMR data of the coumarin 6 were studied to examine any C–F···H–C hydrogen bond interactions. DFT calculations were performed to determine the preferred conformations of the structure that might exhibit a C–F···H–C hydrogen bond. Results and Discussion Synthesis of 2

• these observations (Figure 1 and Figure 3) is that, in solution, rotation of the fluorophenyl ring (about C4–C1’) is permitted but that the average geometry of coumarin 6 has the fluorine atom closer to H5 than H3. The theoretical NMR data for twenty-four conformations of coumarin 6 were obtained from

• 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

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

• prepared compounds perform three kinds of conformations, A, B and C. The hydrocarbon derivatives exhibit conformation A (Figure 5a–a”), whereas the fluorocarbon analogues adopt, depending on whether they carry linking segment C2H4S or not, the conformation B (Figure 5b–b”) or C (Figure 5c–c”). In Figure 6

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• distance between C4 and C13 was smaller by 0.5 Å in the gas phase. The net result of these differences was that intermediate E was more folded in the gas phase, although it was not as dramatically folded as D. The reason for greater folding in the gas phase could have been a tendency to adopt conformations

• plus signs note the location of the cations. Comparison between gas phase and active site model conformations. A) Intermediate D. B) Intermediate E. Mechanism for formation of cyclooctat-9-en-7-ol, published similarly in [42]. Interactions between intermediates and TS structures with active site

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

• optimize geometry, and TD-DFT with a Solvation Model based on Density (SMD) to calculate absorption wavelength maxima. These computational methods have been used successfully with related compounds [16][17]. The relative stability of different conformations of the molecule was calculated, i.e., with the

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• find docking calculations and scoring functions. Out of 40 conformations for each compound, the conformations with lowest free binding energies and S score were selected for visualization by using Discovery studio visualizer DS [47][48]. X-ray structure determination An X-ray quality crystal of 5d was

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

• , 0.012 and 0.087 for 4pzMe-Cl2, 4pzMe-OMe2 and 4pzMe-Pyr2, respectively; see Figure 6 for 4pzH-F2 and 4pzH-Cl2). To experimentally compare the conformations of the E-isomers, we were able to characterize 4pzMe-F2, 4pzMe-Cl2 and 4pzH-F2 by X-ray crystallography (Figure 7). In agreement with the

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• structures of 4 and 9 have one. The cyclohexane rings of all molecules have chair conformations, the cyclohexene rings of all molecules have half-chair conformations, and the furan rings of all molecules have flattened envelope conformations. See Supporting Information File 1 for detailed methods. Genomics

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

• different 1H NMR spectra may account for the existence of several conformations for these constrained coordinated architectures, which still have a certain degree of freedom, that is required for further catalytic properties. Diffusion-ordered spectroscopy (DOSY) 1H NMR was also used on complexes 1a–d (5 mM