Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• or arylcuprates proceeded smoothly to give the desired cyclopropanols (7a–h) after hydrolysis. In all cases, the easily prepared cyclopropanol derivatives were obtained with the methyl, the incoming organometallic and the alcohol in the syn-orientation which was determined through comparison of the

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• regioselectivity is observed. On the other hand, tosylation under aqueous basic conditions has a different reaction mechanism in which p-TsCl occupies the CD cavity prior to the reaction [23]. This orientation of the first tosyl group has a great impact on the substitution of the second tosyl moiety, which can

• in glucopyranose structures: gauche-gauche (gg, 180°), gauche-trans (gt, −60°) and trans-gauche (tg, +60°) [29]. The gg orientation, where both H6 and H6’ are rotated toward the cavity interior and the tosyl group is turned outwards, corresponds to large geminal JH6-H6’ (11.5 Hz) and very small

• vicinal JH6-H5 ≈ JH6’-H5 (<1.5 Hz) coupling constants resulting in one H6,6’ doublet with somewhat broad components. The gt orientation, on the other hand, is associated with small JH6-H5, as in gg, but considerably large JH6’-H5 (≈7 Hz) vicinal coupling constants and gives rise to two signals: a doublet

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• , m) with H-4 (δH 2.20, m) and H3-13 (δH 0.99, s) suggesting these protons were on the opposite orientation. In view of the above evidences, the relative configuration of compound 6 was determined as 4R*,5S*,6R*,7R*. In fact, the only difference between compounds 6 and 6a was the configuration of the

• hydroxy group at C-1 with α-orientation for 6 while β-orientation for 6a [19][20]. Further, due to the influence of the configuration inversions of C-1, the 13C NMR chemical shift of the carbon at C-1 (δC 85.5, qC), was apparently upfield shifted (Δδ = −3.0) comparing to compound 6a (Table 2), giving the

Influence of per-O-sulfation upon the conformational behaviour of common furanosides

• Alexey G. Gerbst,
• Vadim B. Krylov,
• Dmitry A. Argunov,
• Maksim I. Petruk,
• Arsenii S. Solovev,
• Andrey S. Dmitrenok and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2019, 15, 685–694, doi:10.3762/bjoc.15.63

• and β-galactose. Full exploration of the furanoside ring by means of ab initio calculations was performed and coupling constants were calculated for each of the low-energy conformers. The results demonstrated preferred trans-orientation of H4–H5 protons in the non-sulfated molecules which changed to

• gauche-orientation upon sulfation. The effect is less pronounced in the galactosides. For all the studied structures changes in the conformational distribution were revealed by quantum mechanical calculations, that explained the observed changes in intraring coupling constants occurring upon introduction

• : O4–C1–O1–CH2 torsion was set to +60° or −60° depending on α- or β-configuration of the sugar in accordance with the exo-anomeric effect. Other starting torsions in the propyl group had trans-orientation. Geometry optimizations of all the thus obtained structures were carried out at ab initio HF/6-311

Design, synthesis and spectroscopic properties of crown ether-capped dibenzotetraaza[14]annulenes

• Krzysztof M. Zwoliński and
• Julita Eilmes

Beilstein J. Org. Chem. 2019, 15, 617–622, doi:10.3762/bjoc.15.57

• Krzysztof M. Zwolinski Julita Eilmes Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Kraków, Poland 10.3762/bjoc.15.57 Abstract The first crown ether-capped dibenzotetraaza[14]annulenes (DBTAAs), featuring two macrocyclic binding sites fixed in a face-to-face orientation

• macrocyclic components in a face-to-face orientation create a central cavity lined by the two converging binding sites. We decided to make use of the previously reported DBTAA derivatives, bearing 3-bromopropoxy- [31] and 4-bromobutoxybenzoyl [32] pendants, since the presence of rigidifying benzoyl

Conformational signature of Ishikawa´s reagent using NMR information from diastereotopic fluorines

• Laize A. F. Andrade,
• Lucas A. Zeoly,
• Rodrigo A. Cormanich and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2019, 15, 506–512, doi:10.3762/bjoc.15.44

• the Ishikawa´s reagent was analyzed using NMR 3JH,F coupling constant data in different solvents, since the orientation of the diastereotopic fluorines relative to H-2 and F-2 changes with the medium. In nonpolar cyclohexane solvent, the preferred conformation experiences a weaker steric and

• similar systems [15][16][17][18]. In turn, the fluorine gauche effect may result from the gauche orientation between F-1 and F-2, which is sterically and electrostatically disfavored, but it is stabilized by σC–H/C–C → σ*C–F hyperconjugative interactions [19][20][21][22][23]. Recently, electrostatic

• would then be worth to evaluate. It is worth mentioning, however, that the relative and interchangeable orientation of the atoms in a molecule (conformations) is dependent on the medium; while only intramolecular interactions drive the conformational stability of a molecule in the vacuum, the solvent

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• position of the pyridinium core (see Figure 6). This regioselectivity is explained by the particular mutual orientation of the pyridinium cation and the dithionite anion and by the match of interatomic distances between the two negatively charged oxygen atoms in dithionite and the positively charged

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• ’ were considered which would lead to five-membered ring transition states in which the aryl group occupies a preferential pseudo-equatorial or a less favorable pseudo-axial orientation, respectively (Scheme 3) [33][34]. The authors also showed that phosphine oxide (E)-3f could be reduced to the

• rearrangement of cyclopropenylcarbinyl acetates, the observed stereoselectivity was explained by invoking a chair-like transition state model TS4 in which the aryl group preferentially occupies a pseudo-equatorial orientation (Scheme 11) [48]. Although the presence of a halogen atom was tolerated, as

• preferentially occupy a pseudo-equatorial orientation. Additionally, the same sequence applied to the enantioenriched alcohol (R)-25 (ee = 88%) delivered urea (−)-29 with essentially the same optical purity (ee = 86%), thereby indicating that chirality transfer (from C4 to C2) occurred during the sigmatropic

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• strategies, such as photocatalysis or electrocatalysis, can be another orientation for further developments. This review opens the scope for future developments in new methodologies which promise the synthesis of novel fused cyclic systems with a wide range of medicinal and synthetic applications. The

Catalysis of linear alkene metathesis by Grubbs-type ruthenium alkylidene complexes containing hemilabile α,α-diphenyl-(monosubstituted-pyridin-2-yl)methanolato ligands

• Tegene T. Tole,
• Johan H. L. Jordaan and
• Hermanus C. M. Vosloo

Beilstein J. Org. Chem. 2019, 15, 194–209, doi:10.3762/bjoc.15.19

• Ru–N chelation, it needs relatively high energy. In 8 the methyl group is in exactly the opposite orientation to the two α-phenyl groups. Therefore, the steric crowdedness that is observed in 6 that will lead to steric resistance to open the Ru–N chelation does not exist. Thus 8 is more susceptible

Adhesion, forces and the stability of interfaces

• Robin Guttmann,
• Johannes Hoja,
• Christoph Lechner,
• Reinhard J. Maurer and
• Alexander F. Sax

Beilstein J. Org. Chem. 2019, 15, 106–129, doi:10.3762/bjoc.15.12

• other. Attractive interactions reduce the distance between the centers-of-mass of two subsystems, whereas repulsive ones increase the distance. There may also be changes in the relative orientation of the subsystems due to rotations without any change in the distance between the centers of mass. The

• sign of the Coulomb interaction depends only on the signs of the charges. If at least one higher multipole is involved, the interaction also depends on the relative orientation of the multipoles, meaning that it can be attractive, repulsive or that there is no interaction at all. The interaction

• potential between an l-pole and an L-pole can be quite generally written as where Ml and ML are the magnitudes of the l-pole and the L-pole, and is the geometric factor describing the relative orientation of the two multipoles with respect to the line connecting the centers of mass using local spherical

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• ]. The β-orientation of the fluorine substituent in F-ANA leads to a gauche interaction between O4’–C1’–C2’–F2’ favouring the C2’-endo/O4’-endo conformations of the sugar in solution [16][17]. These DNA-like sugar conformations cause that F–ANA is among the few modifications which can trigger the

• ’-fluorinated hexitol nucleic acids FHNA and Ara-FHNA (Figure 1) with the fluorine in axial or equatorial orientation, respectively. Both modifications preferentially adopt a chair conformation with the nucleobase in axial orientation which mimics the C3’-endo conformation of the furanose ring. Thermal

• pseudorotation phase angle P adopting values of 175° (6a) and 181° (6b), respectively. The maximum puckering amplitude νmax was 43° (6a) and 40° (6b). Furthermore, the nucleobase displayed an anti orientation. The carbocyclic ring adopted a chair conformation. As a consequence, the angle γ was aligned in the

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• and 25b this orientation was observed also in the solid state. Some metathesis reactions performed in this study with 24b and 25b in comparison to GII-SIMes and HGII-SIMes are summarized in Table 1. In the model RCM reaction of N,N-diallyl-p-toluenesulfonamide (26, Table 1, entry 1), catalysts 24a and

• , consistently, the same relative orientation between the indenylidene and mesityl unit. Complexes 41–43 were tested in various representative metathesis reactions of standard substrates and compared to the benchmark catalysts IndII-SIMes. Interestingly, all complexes showed a faster catalytic initiation than

• ruthenium complexes by physisorption rather than chemisorption, an unexpected molecular rearrangement of their ligand sphere, determining a cis orientation of the neutral ligands, was observed (113 and 114, Figure 20). The same unusual cis configuration was displayed by complex 115 (Figure 20) upon release

Thermophilic phosphoribosyltransferases Thermus thermophilus HB27 in nucleotide synthesis

• Ilja V. Fateev,
• Ekaterina V. Sinitsina,
• Aiguzel U. Bikanasova,
• Maria A. Kostromina,
• Elena S. Tuzova,
• Larisa V. Esipova,
• Tatiana I. Muravyova,
• Alexei L. Kayushin,
• Irina D. Konstantinova and
• Roman S. Esipov

Beilstein J. Org. Chem. 2018, 14, 3098–3105, doi:10.3762/bjoc.14.289

• equivalent to the concentration of 5-phosphoribosyl-α-1-pyrophosphate (1 mM), it can be assumed that the presence of magnesium ions promotes the proper spatial orientation of the substrate. The reaction also proceeds in the absence of magnesium ions in solution. A similar dependence is observed for TthAPRT

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• orientation and the six-membered ring in a twist-boat conformation (Figure 3b). Approximately 1 kJ/mol higher in energy was the second conformer where the furanose unit adopted a C3’-exo arrangement and the cyclohexene unit a half-chair conformation (Figure 3c). The C(5’) hydroxy group adopted in both

• , −sc). The angle β was found in the +ac or anti orientation, most likely due to either the boat or the twist-boat conformation of the cyclohexene ring. Furthermore, the angle γ was constrained to a +sc arrangement as also found in canonical A- or B-type helices. The torsion angle ε exhibited values in

1,8-Bis(dimethylamino)naphthyl-2-ketimines: Inside vs outside protonation

• A. S. Antonov,
• A. F. Pozharskii,
• P. M. Tolstoy,
• A. Filarowski and
• O. V. Khoroshilova

Beilstein J. Org. Chem. 2018, 14, 2940–2948, doi:10.3762/bjoc.14.273

• contribution of the N−H···O IHB to the stabilisation of the E-forms of 5a–7a appears to be small: in the 1H NMR spectra, the NHa signal is shifted to the low field by less than 1 ppm in comparison with Z-4a (Figure 1) [9]; in a DFT calculation, the mutual orientation of C=NH and the OMe groups is not optimal

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• in a trans-orientation with H(4). In addition, various crystallization tests were carried out in order to confirm the absolute stereochemistry by X-ray diffraction. The chiral 3-(2-(methylthio)ethyl)-1-(phenylamino)-1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)dione (5f) crystallized [44][45][46][47][48][49

Generation of 1,2-oxathiolium ions from (arysulfonyl)- and (arylsulfinyl)allenes in Brønsted acids. NMR and DFT study of these cations and their reactions

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov,
• Olesya V. Khoroshilova and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2018, 14, 2897–2906, doi:10.3762/bjoc.14.268

• the case of the cation Bf, the signals of two isomers were found in the spectra in a ratio of 5 to 1. These isomers appear due to cis-, trans-orientation of t-Bu and ArS groups in the five-membered ring. To the best of our knowledge, this is one of the first examples of full NMR characterization of

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• database [82] was searched for structurally similar compounds leading to the identification of the meta-substituted tetrazole 33 (Figure 7), which was found to have a similar dissociation constant. Moreover, in order to predict the orientation of the fragments in the binding site, molecular docking of 33

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• formation of the E or the Z product is dependent on the orientation of the R groups in this step of the catalytic cycle (Scheme 1). In this short review, we focus on the status of embedding the GH-type catalyst into β-barrel proteins and show their application in various reactions using benchmark substrates

Dispersion-mediated steering of organic adsorbates on a precovered silicon surface

• Lisa Pecher,
• Sebastian Schmidt and
• Ralf Tonner

Beilstein J. Org. Chem. 2018, 14, 2715–2721, doi:10.3762/bjoc.14.249

• placing the cyclooctyne molecule in an upright orientation (molecular C2 axis aligned parallel to the z axis of the cell), with the triple bond aligned parallel to the y axis of the cell, the triple-bond centre located vertically above a lower surface atom (Sidown) at a height corresponding to a vertical

• minimum energy path for this system [8]. Potential energy surface scans were performed by displacing a cyclooctyne molecule in x and y direction while retaining the orientation (equivalent to the starting point of the adsorption energy profile) and a fixed distance Δz(Siup–Ctriple) above the surface. The

• with one adsorbate 1 and unit cell used in the PES scans (orientation of second adsorbate and scan path indicated) shown in Figure 5. Frozen PES scans of 1 along path indicated in Figure 4 (C2 axis parallel to z, C≡C parallel to y, Δz(Siup–Ctriple) = 5 Å) on (a) the clean and (b) the precovered surface

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• characterization data see Supporting Information File 1). The stereochemical orientation of the secondary hydroxy group was determined through X-ray crystal structure of a compound derived from it in a subsequent step. The primary hydroxy group in the diol 6 was then selectively protected to provide the silyl

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

• Nisachon Khunnawutmanotham,
• Cherdchai Laongthipparos,
• Patchreenart Saparpakorn,
• Nitirat Chimnoi and
• Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

• program [19] was used to investigate the orientation of the compounds in the rhAChE binding site. Compounds 4a, 9a, 9b, 9e, 9h, 9i, and 10a were selected as representatives for the docking study. The active site of human AChE, which is at the bottom of a deep and narrow gorge, consists of several major

• active site gorge. The PAS consists of Tyr72, Asp74, Tyr124, Trp286, and Tyr341 [23][24]. From the docking result, the docked orientation of donepezil showed a root-mean-square deviation (RMSD) of 0.474 Å when compared with the conformation in the crystal structure, thereby indicating its potential as a

• the CAS while the chromene rings were located at the PAS. Compounds 9a, 9b, 9e, 9h, and 9i revealed similar orientations in the binding pocket whereas the binding of compounds 4a and 10a was partially different. The orientation of the chromene ring of compound 4a was shifted away from the others

Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5'-azido residues and 5-octadiynyl side chains

• Jiang Liu,
• Peter Leonard,
• Sebastian L. Müller,
• Constantin Daniliuc and
• Frank Seela

Beilstein J. Org. Chem. 2018, 14, 2404–2410, doi:10.3762/bjoc.14.217

• )° and 168.6 (2)° (Figure 2). The triple bond shows a coplanar orientation to the pyrimidine ring with an inclination angle of 1.0 (4)°. The torsion angle χ [46] (−103.6° (2)) is high-anti [47]. This conformation results from restriction caused by the cyclic structure. Most nucleosides including dT (χ

Non-metal-templated approaches to bis(borane) derivatives of macrocyclic dibridgehead diphosphines via alkene metathesis

• Tobias Fiedler,
• Michał Barbasiewicz,
• Michael Stollenz and
• John A. Gladysz

Beilstein J. Org. Chem. 2018, 14, 2354–2365, doi:10.3762/bjoc.14.211

• result (as drawn in Scheme 7, the out,out isomer would be the kinetic product). When the first metathesis does not join the syn positions, as in VIII (front to rear), one phosphorus–boron bond must subsequently be rotated by 180° to create a syn orientation for the second metathesis. Of course, if the