The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• -isomer 91 (>6 kcal/mol), because of the need to attain a cisoid conformation prior to the rearrangement. The thermal vinylcyclopropane rearrangement of ethyl trans-3-(2,2-difluoro-3-phenylcyclopropyl)acrylate (93) proceeded at 100 °C, resulting in the difluorinated cyclopentene 94 with the substituents

Exploring the possibility of using fluorine-involved non-conjugated electron-withdrawing groups for thermally activated delayed fluorescence emitters by TD-DFT calculation

• Dongyang Chen and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2021, 17, 210–223, doi:10.3762/bjoc.17.21

• geometries indicate that the carbazoles adopt a significantly twisted conformation (dihedral angles > 50o) in order to minimize their interaction with the acceptor group. Specifically, for 2CzCF3 the carbazoles are twisted to 60.2o and 70.5o with respect to the bridging phenyl ring while for 2CzSF5, due to

Circularly polarized luminescent systems fabricated by Tröger's base derivatives through two different strategies

• Cheng Qian,
• Yuan Chen,
• Qian Zhao,
• Ming Cheng,
• Chen Lin,
• Juli Jiang and
• Leyong Wang

Beilstein J. Org. Chem. 2021, 17, 52–57, doi:10.3762/bjoc.17.6

• the co-assembly strategy. The cogels show significant CPL emission and stoichiometry-controlled inversion of chirality due to the hydrogen bonding interactions and packing modes in the supramolecular co-assemblies. Owing to TB special V-shaped structure, rigid conformation, and nitrogen stereogenic

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• incorporated deuterium can then be localised through protease-generated peptide fragments or fragmentation within the mass spectrometer. The rate of hydrogen-to-deuterium exchange provides insight into the solvent accessibility. HDXMS provides information on the conformation of the protein, PPIs, and even

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• of calix[4]arene immobilised in the 1,3-alternate conformation led to a system possessing a preorganised ureido cavity hemmed with chiral alkyl units in the near proximity. As shown by the 1H NMR titration experiments, these compounds can be used as receptors for chiral anions in DMSO-d6. The chiral

• different conformations. Although the overwhelming majority of calixarene-based receptors makes use of the cone conformer A (Figure 1), the corresponding diureidocalix[4]arenes in the 1,3-alternate conformation B showed [42][43] surprisingly good complexation abilities towards selected anions. Especially

• reactivity of the nonalkylated phenolic moieties [45]. The fast reaction afforded the corresponding dinitro derivative 3 within a few minutes with 70% yield. As we found in our previous attempts [43][45], the alkylation of dinitrocalixarenes to form the 1,3-alternate conformation is a synthetic challenge. In

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• ) [42]. Probe 6 has a central lysine spacer which is connected to two symmetric peptidic arms. Each arm contains a cationic lysine as a positively charged head group and a pyrene moiety at the end of the γ-aminobutyric acid linker. Compound 6 is mostly in folded conformation in solution and emits pyrene

Naphthalonitriles featuring efficient emission in solution and in the solid state

• Sidharth Thulaseedharan Nair Sailaja,
• Iván Maisuls,
• Jutta Kösters,
• Alexander Hepp,
• Andreas Faust,
• Jens Voskuhl and
• Cristian A. Strassert

Beilstein J. Org. Chem. 2020, 16, 2960–2970, doi:10.3762/bjoc.16.246

• or rotational modes [34][35]. Secondly, a considerably distorted conformation is also needed to prevent detrimental exciton interactions in the solid state. Currently, 6,7-disubstituted naphthalene-2,3-dicarbonitrile derivatives represent an intensively investigated class of compounds, due to their

• dichloromethane/hexane mixture. The structural data are given in Supporting Information File 1 (Tables S1–S3) and the molecular structure in the crystal of Me is shown in Figure 1. The Me derivative is not planar, as it adopts an asymmetrically twisted conformation. The dihedral angles (φ) between the two tolyl

• generate one-dimensional supramolecular chain-like arrays with tolyl units distributed at the two sides of the chain (Figure 2C). These weak forces help the molecules to minimize the energy loss via non-radiative relaxation channels by rigidifying their conformation [25]. Photophysical characterization of

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• the presence of AgNO3 the 3’-O-TBDMS derivative was always obtained in excess over the 2’-isomer. The differences in the reactivity of the 2’- and 3’-OH groups mirror the impact of the sugar conformation, which is dependent on the substitution pattern. Ribonucleosides favor the 3’-endo conformation

• for J2’-3’ after 5'-O-dimethoxytritylation of compound 5 to obtain derivative 6. The clear shift of J1’-2’ can be taken as evidence for a changed sugar conformation, supported by the J1’-2’ coupling constant of 6.1 Hz found in the literature for the 3’-endo conformation of adenosine [32]. Introduction

• of the linker L at C8 in derivative 7 changes the J1’-2’ coupling constant only slightly (4.8 Hz J1’-2’), however, brings in a strong steric effect and most likely induces a preferential syn-conformation of the nucleobase relative to the sugar residue. These effects together can be accounted for the

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

• Thomas Holmstrøm,
• Daniel Raydan and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2020, 16, 2788–2794, doi:10.3762/bjoc.16.229

• change the conformation of the head group, for example, through a ring flip giving rise to an altered amphiphilicity. Yuasa and co-workers have employed a metal-chelating xylopyranoside derivative as the polar head group [11]. The xylopyranoside was functionalized with two amino groups on the 2- and the

• 4-position while having lipophilic tails on the anomeric and the 3-position. This configuration made it possible to chelate Zn2+ ions only when the pyranoside was in the flipped 1C4 conformation. The binding of the metal ions could thereby induce a ring flip that would manifest itself in a decreased

• conformation. When the 3- and 6-position are tethered, for example by metal binding, the glucopyranose ring undergoes a ring flip, bringing together the 2- and 4-position as shown in Figure 1b. Levoglucosan is the ideal starting material for such transformations as the 2- and 4-positions can be functionalized

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• conformations) (Figure 5). Among the 18 conformations, the structure with an equatorial conformation of the but-2-ynyl group, an anti-arrangement of the O–C bond and the prop-1-ynyl group, and an s-trans conformation of the diene system proved to be the most stable by more than 7 kJ/mol (Figure 6). Of course

• , this conformation cannot enter a Diels–Alder reaction and hence the more stable s-cis conformation with otherwise identical conformational arrangement of the other two parameters, although less stable by about 9 kJ/mol, was considered as the starting geometry for the Diels–Alder reaction (Figure 6

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

•  2B and Figure 2E, the CD spectra of 1 and 2 exhibit a negative peak at 210 nm, suggesting that the peptides can adopt a β-strand conformation to form nanofibrils. During the transition from micelles to fibrils, the CD signal at 210 nm reverses the sign, likely due to the self-assembly of Nap-ffky to

• helical fibrils. Analyzing the CD spectra by the Contin-LL analysis program [48], we estimated the percentage of each conformation, further confirming the trend and the assignment of the dominant conformation. As shown in Figure 2C and Figure 2F, the initial state of peptide 1 has more β-strand

• conformations than that of peptide 2. With increasing proteolysis time, the CD spectra indicate that the cleavage of 1 or 2 results in more assemblies that favor β-strand conformations (Figure 2D and Figure 2E). In addition, the ratio of the β-strand conformation resulted from the cleavage of 1 being slightly

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• mode of nucleophilic attack on the imine double bond in 1. As presented in Figure 3, imine 1 might react in the most stable conformation with the bulky tert-butyl group pointing away from the imine double bond. In this case the only stereocontrolling factor in play is the difference between the

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

• (Figure 2), which was among the higher-energy calculated conformers of 2 (see Supporting Information File 1), bears a close resemblance to the solid-state conformation of piperine (1, Figure 1). The structure 2f has a F–C–C–F dihedral angle of 57° and a F–C–C=O dihedral angle of –133°. These angles

• relative activities of 1 vs 2 in the AChE vs BACE-1 assays. One possibility is that analog 2 is induced to adopt the “correct” conformation when binding to both targets (i.e., 2f, Figure 2), and this structure fits well within the AChE active site but poorly within the BACE-1 active site, perhaps due to

• unfavourable interactions of the fluorine substituents of 2 with BACE-1 active site residues. A second possibility is that 2 adopts an “incorrect” conformation upon binding to both targets (e.g., 2a, Figure 2), and this novel molecular shape is readily accommodated by AChE [35] but not by BACE-1, perhaps due

A consensus-based and readable extension of Linear Code for Reaction Rules (LiCoRR)

• Benjamin P. Kellman,
• Yujie Zhang,
• Emma Logomasini,
• Eric Meinhardt,
• Karla P. Godinez-Macias,
• Austin W. T. Chiang,
• James T. Sorrentino,
• Chenguang Liang,
• Bokan Bao,
• Yusen Zhou,
• Sachiko Akase,
• Isami Sogabe,
• Thukaa Kouka,
• Elizabeth A. Winzeler,
• Iain B. H. Wilson,
• Matthew P. Campbell,
• Sriram Neelamegham,
• Frederick J. Krambeck,
• Kiyoko F. Aoki-Kinoshita and
• Nathan E. Lewis

Beilstein J. Org. Chem. 2020, 16, 2645–2662, doi:10.3762/bjoc.16.215

• , “ G ” represents glucopyranose, the pyranose conformation of glucose, with ᴅ stereospecificity. Glucopyranose with ʟ stereospecificity is written as “ G’ ” (SRS1). Glucofuranose with ᴅ stereospecificity is written as “ G^ ” (SRS2), and glucofuranose with ʟ specificity is written as “ G~ ” (SRS3

Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes

• Henrik Hupatz,
• Marius Gaedke,
• Hendrik V. Schröder,
• Julia Beerhues,
• Arto Valkonen,
• Fabian Klautzsch,
• Sebastian Müller,
• Felix Witte,
• Kari Rissanen,
• Biprajit Sarkar and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209

• synthesized in moderate yields of 24% and 26%, respectively, over three steps from the same two building blocks, the ditosylate 5 and the monobutyl-protected NDI precursor 7 (Scheme 1). The connectivity and conformation of exTTFC7 was observed in the crystal structure obtained from crystals generated through

• Information File 1). Slow diffusion of CH3CN into a concentrated solution of NDIC7 in CH2Cl2 yielded single crystals suitable for X-ray diffraction (Figure 2b). The macrocycle displays a folded conformation in the solid state due to the flexible linker, featuring an intramolecular NDI/naphthalene stacking

• non-folded conformation. The torsional angle between the central phenyl ring and the NDI is 84.2° in order to avoid strain between the protons of the resorcinol and the carbonyl groups of the NDI. Consequently, an intramolecular π–π-interaction with the naphthalene on the other side of the macrocycle

Synthesis of novel fluorinated building blocks via halofluorination and related reactions

• Attila Márió Remete,
• Tamás T. Novák,
• Melinda Nonn,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2020, 16, 2562–2575, doi:10.3762/bjoc.16.208

• is the formation of only a single halonium ion intermediate is possible. According to the Fürst–Plattner rule (ring-opening into a chair conformation is preferred over a twist boat conformation), the formation of the products (rac)-2a,b is expected (Scheme 1). Indeed, halofluorinations of (rac)-1

• NOESY was unsuccessful. The reason is that cyclohexenes have a half-chair conformation, and the hydrogen atoms to undergo important NOESY interactions are simply too far away from each other. To solve this problem, the olefin bond of (rac)-35 was hydrogenated to a cyclohexane, affording the fluorinated

• dimethyl cyclohexanedicarboxylate (rac)-36. The change of the conformation from a half-chair to an ordinary chair enabled the determination of the stereochemistry of (rac)-36 by NOESY measurements. Since the saturation of (rac)-35 did not affect the configuration of the CHF motif, that structure was

Water-soluble host–guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres

• Si-Yuan Liu,
• Xin-Rui Wang,
• Man-Ping Li,
• Wen-Rong Xu and
• Dietmar Kuck

Beilstein J. Org. Chem. 2020, 16, 2551–2561, doi:10.3762/bjoc.16.207

• the slight shift of the peaks further indicates the successful complexation of TBTQ-(OG)6 and C60. Simulations of complex TBTQ-(OG)6 C60 in water. In spite of numerous attempts, we failed to obtain good-quality crystals to determine the binding conformation of complex TBTQ-(OG)6 C60 by X-ray

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

• under observation, could be readily applied to other binding problems as part of a general strategy in drug design or mechanistic analysis. Keywords: binding; conformation; Galaxy; glycoprotein; in silico; Introduction A typical sequence of events in research and discovery is noticing a critical

• conformation of the peptide portion of the antigen and does not bind directly. Previous studies have shown that O-glycosylation may provide increased physical stability [20], rigid conformations for protein stability [21], induce the formation of stiff and extended peptide conformations [22], and may affect

Leveraging glycomics data in glycoprotein 3D structure validation with Privateer

• Haroldas Bagdonas,
• Daniel Ungar and
• Jon Agirre

Beilstein J. Org. Chem. 2020, 16, 2523–2533, doi:10.3762/bjoc.16.204

• ], glycosidic linkage stereochemistry [14] and torsion [15][16], and most recently, ring conformation [17]. Most of these issues have now been addressed as part of ongoing efforts to provide better software tools for structure determinations of glycoproteins, although the most difficult cases remain hard to

• monosaccharide minimal-energy conformation. While these features were recognised to address some long-standing needs in carbohydrate structure determination [39][40], significant challenges remain, particularly in the scenario where the glycan composition cannot be ascertained solely from the three-dimensional

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• crystallization. Crystallization seems to succeed best for ligands that can adopt a defined conformation upon binding without flexible loops protruding from the protein surface. Even in these cases, the ligand is preferably found at binding sites that are facing solvent channels but at the same time enable

• residues over others as well. The smallest calix[4]arene is confined to a bowl-shaped conformation and entraps mostly lysine side chains, however, occasionally an arginine residue is favored over lysine residues [80][82]. The larger calixarenes are more flexible, and different conformations have been found

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

• lipophilicity with the molecular conformation. Keywords: dipole moment; fluorinated compounds; gauche effect; herbicides; log P; Introduction Whilst in the last years the agrochemical industry has encountered a period of downturn affected by new regulations, low crop prices, biochemical resistance, among

• 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

• macroscopic observed properties, such as lipophilicity [13]. Accordingly, the main goal of this work is to investigate the relationship between lipophilicity and molecular conformation on a set of organofluorine agrochemicals. To this end, this study has been divided in two parts. First, we have analyzed the

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

• with 3D information (furanose/pyranose shape, configuration, anomericity, and ring conformation). Glycosidic linkages can be easily defined, as the values of the dihedral angles (Φ, Ψ, Ω). They can be manually set or extracted from a database of low energy conformations of 600 disaccharide segments

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

• ) was the linking step, and ester saponification was the cutting step. A potential problem with this approach was that the macrocycles were highly flexible and thus they might adopt a closed conformation hindering the necessary threading step. The flexible tails made the compounds soluble, but also

• precedents from the Stoddart [6][24][25], Gibson [26], Loeb [27], and Sanders [28] groups. Furthermore, host 1 was designed to be rigid so that the two macrocycles would maintain an open conformation which is required for the threading step. The approach is modular, such that one host can be paired with

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• protons (see Scheme 1) and therefore suggested the preferred s-trans conformation of the β-styryl substituent in a CDCl3 solution (see Supporting Information File 1). It should be noted that the attempted N1-cycloalkylation did not proceed with cyclopropyl- and cyclohexylboronic acids. Aiming at extending

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• conjugate Dex-1b in aggregates or nanoparticles. Moreover, it is known that dye conjugation to a polymer even in small percentages can generate a large change in the environment of the chains affecting conformation and chain organization [36]. To assess the influence of hydrophobicity on the formation of