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

• variation of the pseudorotation phase angle P at the range of the maximum puckering amplitude νmax and was visualized in the pseudorotation wheel (Figure 3a). The two low energy regions appeared in the Southern hemisphere. The lowest energy conformer was associated with the furanose unit in a C2’-endo

• 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

• conformers a pseudoaxial position. Consequently, the torsion angle γ was aligned in a +sc arrangement (C2’-endo conformer: 64°; C3’-exo conformer: 83°). The distance between the fluorine atom and the C(5’) oxygen was 3.3 Å in the C2’-endo conformer and 2.9 Å in the C3’-exo conformer. These two conformers

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

• reflected in the Lewis structure is the tilting of the molecule upon adsorption leading to a chair-like conformer bending over the dimer rows on the surface [7]. Starting from this precovered surface (i.e., decorated with one adsorbate in the unit cell), we now investigate the adsorption of a second

Calixazulenes: azulene-based calixarene analogues – an overview and recent supramolecular complexation studies

• Paris E. Georghiou,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Hidetaka Nishimura,
• Jaehyun Lee,
• Atsushi Wakamiya and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2018, 14, 2488–2494, doi:10.3762/bjoc.14.225

• determinations were made on the possible major conformations, based upon those previously defined in reference [20]. Three distinct conformations (saddle, cone and 1,2-alternate) shown in Figure 2, were generated. Significantly, whereas for 3 which was based upon its X-ray structure, a partial cone conformer

• Table 2 with the saddle conformer (Figure 2c) having the lowest energy. Nevertheless, when subjected to geometry optimizations with the individual respective TRAX salt guests, the saddle conformer opened up to generate and accommodate each of the guests in typical “guest-in-cone” structures, as can be

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• -cation dimer (TTF●+)2. However, the Coulombic repulsion in this six-fold charged complex destabilizes the radical-cation dimer and the system converts into a second stable co-conformation in which both dihydroxynaphthalene units are inside the cavity of the wheel. To achieve this conformer, two types of

Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes

• Carmine Gaeta,
• Carmen Talotta and
• Placido Neri

Beilstein J. Org. Chem. 2018, 14, 2112–2124, doi:10.3762/bjoc.14.186

• presence of a less abundant conformer of 1. The nature of this minor conformer can be inferred by the work of Reinhoudt and co-workers which showed [41] that the conformations preferentially adopted by calix[6]arene hexaethers are the cone and 1,2,3-alternate ones. In accordance, 2D COSY and HSQC spectra

• of 1 at 233 K clarified that this minor conformer was the cone one through the presence of an AX system at 3.35/4.42 ppm (COSY), which correlates with a carbon resonance at 29.1 ppm (HSQC), related to syn-oriented Ar rings (cone conformation). The coalescence temperature of the methylene protons was

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• and 93:7 β:α, respectively (Table 1, entries 1 and 2) to a β:α ratio of 66:34 (Table 1, entry 9). These ratios can be explained by the mechanism of the Ritter reaction. The oxocarbenium ion 9 exists as an equilibrium of two conformer half-chair forms 9a and 9b (Scheme 5). Theoretical investigations of

• substituted cyclic oxocarbenium ions showed for oxocarbenium ions with electronegative substituents that two positions from the ring oxygen the conformer with this substituent in an axial position is favored. This can be explained by a through space electrostatic interaction of the partially negatively

• charged substituent and the positively charged ring. With the axial substituent these charges are closer together and the conformer is preferred [36][37][38]. By application of these assumptions to our system, we suggest that 9a should be the main conformer. A second argument for the dominance of 9a is

A pyridinium/anilinium [2]catenane that operates as an acid–base driven optical switch

• Sarah J. Vella and
• Stephen J. Loeb

Beilstein J. Org. Chem. 2018, 14, 1908–1916, doi:10.3762/bjoc.14.165

• + can be protonated to yield [8-HDB24C8]7+ in two different co-conformations A and B. b) The partial 1H NMR spectrum (500 MHz, 298 K, CD3CN) of [8-HDB24C8]7+ shows key resonances for both co-conformations A (red) and B (blue). See Scheme 1 for labelling; atoms of co-conformer B are labelled with a prime

Host–guest complexes of conformationally flexible C-hexyl-2-bromoresorcinarene and aromatic N-oxides: solid-state, solution and computational studies

• Rakesh Puttreddy,
• Ngong Kodiah Beyeh,
• S. Maryamdokht Taimoory,
• Daniel Meister,
• John F. Trant and
• Kari Rissanen

Beilstein J. Org. Chem. 2018, 14, 1723–1733, doi:10.3762/bjoc.14.146

• conformer space in these simulations, no constraints were enforced on either N-oxide or acetone molecules. The low energy structures obtained from these OPLS-2005 searches were then further analysed using DFT-based techniques [45][46][47]. The resulting optimised geometries of the 3@BrC2, 3@BrC3 and 3@BrC6

The phenyl vinyl ether–methanol complex: a model system for quantum chemistry benchmarking

• Dominic Bernhard,
• Fabian Dietrich,
• Mariyam Fatima,
• Cristóbal Pérez,
• Hannes C. Gottschalk,
• Axel Wuttke,
• Ricardo A. Mata,
• Martin A. Suhm,
• Melanie Schnell and
• Markus Gerhards

Beilstein J. Org. Chem. 2018, 14, 1642–1654, doi:10.3762/bjoc.14.140

• binding motifs. However, distinct differences were found between the two methods: While B3LYP-D3 predicted the OH–E conformer as the most stable complex SCS-CC2 gave OH–P as the lowest minimum (cf. Table S1 in Supporting Information File 1). This is in contrast to our results of diphenyl ether–alcohol

A conformationally adaptive macrocycle: conformational complexity and host–guest chemistry of zorb[4]arene

• Liu-Pan Yang,
• Song-Bo Lu,
• Arto Valkonen,
• Fangfang Pan,
• Kari Rissanen and
• Wei Jiang

Beilstein J. Org. Chem. 2018, 14, 1570–1577, doi:10.3762/bjoc.14.134

• exchange is now slow on the NMR timescale (Figure S7c in Supporting Information File 1). Only two signals for the aromatic protons of the host are observed, suggesting that ZB4 predominantly exists as either conformer I or IV in the complex 10+@ZB4. However, it has been not clear which one ZB4 adopts

• . Fortunately, a single crystal suitable for X-ray diffraction could be obtained by slow evaporation of the solution of 10+ and ZB4 in a mixture of CH2Cl2 and CH3CN. The crystal structure clearly shows that conformer I (Figure 1d) is the selected conformation by guest 10+. TA4 shows a large amplitude of

• conformer III (C2h symmetry) [37] to be the most favored conformation for all complexes. Obviously the conformational network of ZB4 shows no response to the electronic substituents on the guests. This is quite different from TA4. In addition, there has been a linear free energy relationship between

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• in the presence of NaH or n-BuLi (Figure 5) [46]. Conformational analysis of calixarene-diphosphite ligands revealed that presence of sterically hindered groups led to the formation of the predominantly cone-conformer. In order to check whether calix[4]arene-diphosphite ligands may also serve as

London dispersion as important factor for the stabilization of (Z)-azobenzenes in the presence of hydrogen bonding

• Andreas H. Heindl,
• Raffael C. Wende and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 1238–1243, doi:10.3762/bjoc.14.106

• [12] and show reversible isomerization from the thermally stable E- to the Z-isomer upon irradiation with UV light. The metastable Z-azobenzene re-isomerizes to the E-conformer either thermally or upon irradiation with visible light [13][14]. Interestingly, the thermal stability of azobenzene isomers

• are possible for the stabilization of Z-azobenzenes 4–7. To estimate the influences of those effects, a conformer distribution analysis was performed to identify low-lying conformations of the corresponding (Z)-azobenzenes. The energetically favored conformers found (within 1.5 kcal mol−1 for 4 and 5

• kcal mol−1 for 5–7, respectively, relative to the lowest energy conformer) were then re-optimized at the B3LYP/6-31G** [26][27][28][29] level of theory with and without D3(BJ) [30][31] dispersion correction (gas phase) (conformations of one enantiomer of each diastereomer of 4 were analyzed. The

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• various conformers of the permethylated furanosyl oxocarbenium intermediate revealed that the E3 conformer with the C5'–OMe oriented over the positively charged furanosyl ring (Figure 6C) has a large stabilizing effect due to C5'–O5 dipole interactions. In addition, the C2' pseudoequatorial methoxy and C3

• ' pseudoaxial methoxy groups further stabilize the intermediate in E3 conformer, thereby favoring the E3 confomer over the 3E. In the case of an anomeric phenyl group (Ph, Figure 6C), stabilization of the positive charge (C=O+) through conjugation, via parallel alignment, helps to overcome the unfavorable

• steric interactions between the C2'–OMe and the Ph group [81]. Because E3 is the favored conformer, an inside attack of the nucleophile (H−) results in an α orientation in the final product, which is evident from the the synthesis of 1 (OBn-substituted Pseudouridine, Figure 6D). Despite the greater

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• conformer A, conformer B should be favored. Assisted by the chloride, this species is deprotonated forming the condensation product 4h with an (E)-configured double bond. Obviously, this formal dehydration is possible only in the presence of electron-donating para-substituents in the benzaldehyde. In order

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• observed by NMR spectroscopy in DMSO solution (≈10:7). Interestingly, for 15a, the major conformer corresponds to a rotameric state with a screened N1 atom, but in the major conformer of 15b, the N2 atom of the heterocycle is screened. Notably, similar structural disorder was previously observed in the

A permutation approach to the assignment of the configuration to diastereomeric tetrads by comparison of experimental and ab initio calculated differences in NMR data

• Przemysław J. Boratyński

Beilstein J. Org. Chem. 2017, 13, 2478–2485, doi:10.3762/bjoc.13.245

• shieldings (Equation 3). The geometries for tetrads 1–3 were also reoptimized using the 6-311G+(2d,p) basis set and the GIAO calculation was redone using mPW1PW91 functional and the same basis set as recommended by Tantillo [3] where Ej is the relative energy of conformer j, σij is isotropic shielding for

• atom i in conformer j. An example of scoring of all permutations based on 13C NMR data for tetrad 1 is shown in Table 2 (for all data, see Supporting Information File 1). For all the compounds comparison of the 13C NMR data identified the permutations corresponding to proper configuration assignment

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• intermediate J values is consistent with two major conformations of 6a existing in equilibrium (Figure 2). The first conformer (left) has an extended zigzag structure. This matches the geometry that was observed in the X-ray crystal structure for the anti,syn-trifluoroalkane 40a [17]. The second conformer

• conformational averaging could be occurring about this bond. Overall, the pattern of large, small and intermediate J values is consistent with two conformations of 6b existing in equilibrium (Figure 2). The first conformer (left) has a bent structure. This provides gauche alignments between all pairs of vicinal

• C–F and C–N bonds, whilst avoiding 1,3-dipolar repulsion [11][12][43]. The second suggested conformer of 6b (right) has an extended zigzag structure. This geometry is counterintuitive, because although it provides gauche alignments between all pairs of vicinal C–F and C–N bonds, it includes an

Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by ¹H NMR spectroscopy

• Yoshihiro Nishida,
• Mengfei Yuan,
• Kazuo Fukuda,
• Kaito Fujisawa,
• Hirofumi Dohi and
• Hirotaka Uzawa

Beilstein J. Org. Chem. 2017, 13, 1999–2009, doi:10.3762/bjoc.13.196

• , namely gt(+), gg(−) and tg, were randomized, while in more polar solvents, the gt(+) conformer with (+)-helicity was amplified at the expense of gg(−) and tg conformers. The sn-3 phosphocholine in phosphatidylcholine exhibited a greater effect on the gt(+) conformer, which was independent of the solvents

• (+) and gg(−) conformations around the 1,2-diacyl moiety (Figure 1). From X-ray crystallography data, a common structure in which the 1,2-diacyl chains are aligned in parallel is observed, which adopts either the gt(+) or gg(−) conformer [7][10][12]. An analogous conformation has been reportedly observed

• conformational properties of a series of 1,2-dibenzoyl-sn-glycerols bearing different sn-3 substituting groups were examined. As shown in Figure 1, gt(+) is one of the gauche conformers with a right-handed (+)-helicity around 1,2-diol, while gg(−) is another gauche conformer with an antipodal left-handed

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

• José Enrique Barquera-Lozada and
• Gabriel Cuevas

Beilstein J. Org. Chem. 2017, 13, 1969–1976, doi:10.3762/bjoc.13.192

• elemanes formed via a Cope rearrangement from germacranolides only depends on the configuration of the most stable germacrane conformer since it is mainly a concerted reaction [15][18][33]. It is accepted that the conformers that normally carry out a Cope rearrangement are the ones that have crossed double

• coordinate of these four mechanisms. In the first proposed mechanism (path M, Figure 1) a conformational transformation of 1 must occur first. The most stable conformer has chair-boat conformation that according to Samek nomenclature is [15D5,1D14] (1a). This conformer is the one that is present in solution

• [37]. Nevertheless, conformer 1a does not have the proper geometry to directly generate the correct stereochemistry of 3. Both C–C bonds next to the C10–C1 double bond of conformer 1a have to rotate to generate the boat-boat conformer (1b, [15D5,1D14]), which is 3.5 kcal/mol less stable than 1a, but

Conformational impact of structural modifications in 2-fluorocyclohexanone

• Francisco A. Martins,
• Josué M. Silla and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2017, 13, 1781–1787, doi:10.3762/bjoc.13.172

• physicochemical/biological property of interest. In this work, structural changes in 2-fluorocyclohexanone were theoretically studied with the aim at finding intramolecular interactions that induce the conformational equilibrium towards the axial or equatorial conformer. The interactions evaluated were hydrogen

• gauche effect, but this did not appear, because of a predominant σC–H2 → π*C=O interaction in the equatorial conformer. The conformational induction through simple structural modifications can play an important role in the stereoselectivity of reactions (kinetically dependent on the conformation of the

• axial conformer. The axial conformer provides a gauche arrangement between the fluorine atom and the endocyclic group, while electron delocalization from electron donors, such as a σCH orbital to the vicinal π* orbital, as well as the spatial interaction between the fluorine substituent and the

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• attack on the least hindered face of a 1,2-chelated conformer (Figure 5C bottom, right). On the other hand, the minute formation of the 5’R-isomer that would be explained by the Felkin–Ahn model (Figure 5D bottom, left) is strongly disfavored due to the the bulkiness of the silyl groups hampering an

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• phenomenon could be rationalized by a different conformer population in the solution compared to solid state. This hypothesis was preliminary confirmed by the results of variable-temperature NMR experiments summarized in Supporting Information File 1 (Figures S1–S6). Another potentially useful criterion for

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• Ahlrichs’ basis set TZVP (triple zeta valence plus) polarization [30]. The number of excited states per each molecule was 24. The ECD spectra were generated by the program SpecDis [31] using a Gaussian band shape from dipole-length dipolar and rotational strengths. Equilibrium population of each conformer

• at 298.15 K was calculated from its relative free energies using Boltzmann statistics. The calculated spectra were generated from the low-energy conformers according to the Boltzmann weighting of each conformer in MeOH solution. For theoretical investigations on the photoinduced interconversion

Conformational study of L-methionine and L-cysteine derivatives through quantum chemical calculations and ³J_HH coupling constant analyses

• Weslley G. D. P. Silva,
• Carolyne B. Braga and
• Roberto Rittner

Beilstein J. Org. Chem. 2017, 13, 925–937, doi:10.3762/bjoc.13.94

• (NCI) analyses were used. Results and Discussion Esterified derivatives of L-Met and L-Cys The lowest-energy conformers of 1 and 2 and their calculated parameters (ωB97X-D/aug-cc-pVTZ) in gas phase and in solution (IEF−PCM) are shown in the Figure 1 and Table 2, respectively. Each conformer of 1 and 2

• investigated media. As well as for 1, geometries of 2 do not present significant variations when ε is increased. It also demonstrates that the solvent effect does not affect the conformer populations of 2. To obtain more details about the solvent effect in the conformational isomerism of the studied compounds

• on the dihedral angle H−C−C−H, according to the well-known Karplus relationship [25]. As the observed 3JHH,obs coupling constant represents a weighted average of the contribution of each conformer, the calculated 3JHH,calc spin−spin coupling constant represents the individual 3Ji coupling constant

The effect of cyclodextrin complexation on the solubility and photostability of nerolidol as pure compound and as main constituent of cabreuva essential oil

• Joyce Azzi,
• Pierre-Edouard Danjou,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2017, 13, 835–844, doi:10.3762/bjoc.13.84

• narrow side of CD. Molecular modelling The theoretical molecular modelling is useful to illustrate the most energetically favorable three-dimensional structure of the inclusion complex in solution. The inclusion complex conformer that presents the weakest relative binding energies (ΔE) (i.e., the most

• stable conformer) is represented in Figure 4b. The results showed that the formation of the β-CD/trans-Ner inclusion complex is an energetically favorable process and that the inclusion mode is coherent with the experimental NMR results. Photodegradation studies of Ner To the best of our knowledge, no

• diagrams of CD/trans-Ner inclusion complexes. Phase solubility profile of cabreuva EO obtained by the TOC method. a) 2D ROESY spectrum of β-CD/trans-Ner inclusion complex in D2O and b) representation of the most stable inclusion complex conformer. Photodegradation kinetics of cis-Ner (a), trans-Ner (b