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

• possibilities are ongoing. Examples of calix[n]arenes 1 and calix[4]azulenes 2–5. Three major computed conformers of OPC4A; a: 1,2-alternate; b: cone and c: saddle. Geometry-optimized (ωB97xD/6-31G(d)) and (ωB97xD/GenECP) structures, respectively, computed for left: (a) 5TBACl; (b) 5TBABr; and (c) 5TBAI; right

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• conversion to the diastereomer by oxidation and reduction. Conformational analysis of some of the resulting diols obtained under McMurry conditions was complicated by the presence of several conformers of similar energy. The pinacol coupling appears to start at the ketone, as indicated by the selective

• two conformers in CDCl3. Thus, it was to be explored how open-ring cyclohexadiene precursors would be synthesized and behave under McMurry conditions, and how stable the resulting [8.4.0]bicycles would be. Normally, McMurry conditions lead to the formation of alkenes, but medium-sized ring 1,2-diols

• ). For diastereomer 19, 2-H did not show a NOESY correlation to 5-Hβ, but instead a correlation to 14-H, to the isopropyl methine hydrogen, and to 3-CH3. In addition, 3-CH3 correlates with both methylene hydrogens at C4. We found only two conformers of the (2S,3S,14R) diastereomer that meet those

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

• conformations of the 5’-azido compounds 7 and 2 as well as dC macrocycle 4 were investigated in solution. To this end, high resolution spectra (600 MHz NMR) were measured in DMSO-d6 and the population of S vs N conformers (Supporting Information File 1, Table S2) were calculated using the program PSEUROT

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

• be further forced towards 9a. Since in both conformers one R2 is axial and the other is equatorial the bulkiness of R2 should have no influence on the equilibrium. Both conformers can be attacked by 8 from two different sides, where each one leads to an addition product in chair conformation or to a

• conformers 9a and 9b. Neighboring group participation of ester protective groups. For better clarity C-2 is not shown in conformers 9a and 9c. Pd catalyzed Tsuji–Trost reation. BSA: N,O-bis(trimethylsilyl)acetamide, DMM: dimethyl malonate. Synthesis of spiro-fused oxazolines 10 and 11 via Ritter reaction

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• chemical calculations were done in several steps: selection of optimal conformers; organization of initial complex geometry; complex optimization procedure. The conformers search procedure has been done only for calix[4]arene’s triazolyl substituents due to complexity of the whole molecule. Conformers of

• MOPAC 2016 program [61] with discard of repeated duplicates. Then unique conformers were combined with calix[4]arene core, and corresponding cations and complexes with ATP/ADP were optimized by DFT calculations. For DFT calculations Priroda 16 program [62] with build-in PBE functional on L2 basis level

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• force field and 30 different conformers of each ligand were docked into two different X-ray structures of FimH (for details see Supporting Information File 1). These two crystal structures differ in the conformation of the tyrosine gate, formed by Y48 and Y137 positioned at the entrance of the

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

• auxiliary Coulomb fitting basis set (cbas) for the resolution-of-identity approximation (RI) for which def2-TZVP-cbas was chosen [60]. All obtained geometries were confirmed as minima by harmonic frequency calculations. In order to evaluate the relative stability of the different conformers found on the

• confirmed the subtle difference between the six conformers, with an energy span of approximately 4–5 kJ/mol (≈1 kcal/mol, the commonly accepted definition of chemical accuracy) among all structures. Also featured in Table 1 are the computed O–H stretch fundamentals together with the IR intensity at the two

• significantly. The moiety with the largest potential as dispersion energy donor (DED) is the phenyl ring. This results in the strongest stabilization for the two conformers whereby the methanol is closest to the ring (OH–P and OH–P’). The other conformers have much more spread out contributions. What is

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

• macrocycles possess multiple conformers due to the naphthalene flipping in analogy with the phenyl-ring flipping seen in the more common calixarenes. The conformers so formed undergo quick interconversion and each one has a slightly different cavity. Thus, these conformers consist of a complex conformational

• solutions and the different conformations in the solid state may result from the packing of the different lower-rim alkyl groups. For the conformers with cavities (Scheme 1b), three out of the four have been predominantly selected by three different guests. For example, guests 2+ and 3+ induced conformers

• = −0.13, R2 = 0.9956) and TΔS (right, slope = 0.93, R2 = 0.9976). (a) Chemical structures of ZB4 and the guests involved in this research. The counterions are PF6−. (b) The four representative conformers of ZB4 resulting from naphthalene flipping. Numberings on the structures are used to assign NMR

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

• -substituted moieties in (Z)-4–7 make intramolecular stabilizing interactions unlikely. Nevertheless, it can be envisioned that the freely rotatable Ar–CH2–Ar units should allow the formation of close proximity conformers of (Z)-4a in solution, in which attractive interactions, such as hydrogen bonding and

• 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

• with D3(BJ) dispersion correction, as well as the close H–H contacts in all compounds of about 2.4 Å to 3.0 Å support the stabilizing effect of LD interactions in (Z)-azobenzenes 4–7. Figure 1 visualizes the computational findings for the compared conformers of (Z)-4. A noncovalent interaction (NCI

Local energy decomposition analysis of hydrogen-bonded dimers within a domain-based pair natural orbital coupled cluster study

• Ahmet Altun,
• Frank Neese and
• Giovanni Bistoni

Beilstein J. Org. Chem. 2018, 14, 919–929, doi:10.3762/bjoc.14.79

• , and London dispersion terms. Herein, this technique is employed in the study of hydrogen-bonding interactions in a series of conformers of water and hydrogen fluoride dimers. Initially, DLPNO-CCSD(T) dissociation energies for the most stable conformers are computed and compared with available

• . This information is used to rationalize the trend of stability of various conformers of the water and hydrogen fluoride dimers. Keywords: DLPNO-CCSD(T); hydrogen-bond interaction; interaction energy; local energy decomposition; London dispersion; Introduction Hydrogen bonds are of fundamental

• interaction, they also provide useful interpretative frameworks in which to discuss experimental observables. For instance, they can be used for discussing trends of dissociation energies [8][9] or the relative stability of conformers [11][15][18][19]. However, two fundamental aspects must be considered when

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

• in turn, is affected by the nature of the C2', C3' and C5' substituents [80][81]. Codée and coworkers elaborated on the mechanism and stereochemistry of this reaction by calculating the energies of different oxocarbenium conformers using a free energy surface (FES) mapping method [80][81]. These

• studies were based on the Woerpel’s model comprising of two stable conformers, namely 3E and E3, in equilibrium (Figure 6B) [84][85]. The nucleophile approaches from the side presenting the least number of eclipsing interactions with the C2' substituent (Figure 6B) [80]. Examining the energies of the

• 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

An uracil-linked hydroxyflavone probe for the recognition of ATP

• Márton Bojtár,
• Péter Zoltán Janzsó-Berend,
• Dávid Mester,
• Dóra Hessz,
• Mihály Kállay,
• Miklós Kubinyi and
• István Bitter

Beilstein J. Org. Chem. 2018, 14, 747–755, doi:10.3762/bjoc.14.63

• complex were computed. Foremost, a molecular mechanical (MM) conformation analysis was performed for the individual molecules using the MMFF force field [47]. The stable conformers were optimized further at the density functional theory (DFT) level using the PBE functional [48][49] with D3BJ dispersion

• and rings A and B of the flavone. The alignment of the flavones and ATP components is similar as in DMHF∙ATP, obtained by a computer aided simulation [34]. For the UHF∙ATP complex, two structurally rather different stable conformers were found in the calculations. In the first case (Figure 2b), the

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

• under liberation of a chloride. For the formed oxonium ion, two conformers A and B are possible due to free rotation around the single bond neighboring the SF5 group and the former benzylic carbon atom (Scheme 4). Due to the possible repulsive interaction of the SF5 group with the quinoid ring in

Halogen-containing thiazole orange analogues – new fluorogenic DNA stains

• Aleksey A. Vasilev,
• Meglena I. Kandinska,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• David Sucunza,
• Juan J. Vaquero,
• Obis D. Castaño,
• Stanislav Baluschev and
• Silvia E. Angelova

Beilstein J. Org. Chem. 2017, 13, 2902–2914, doi:10.3762/bjoc.13.283

• irradiation at 532 nm by 80 mW continuous wave frequency doubled DPSS (diode pumped solid state) laser, (Figures S21–S24, Supporting Information File 1). Computational studies Optimized structures of the preferred conformers of the cationic fragments of all dyes with the counterion I− (in the preffered

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• sequential Hαi–HNi+1 ROEs have much higher intensities than intra-residual Hαi–HNi ROEs. Few sequential HN–HN ROEs with weak intensities could be observed, indicating that turn or helical conformers are sparsely populated. Because of its Karplus dependence upon main chain φ dihedral angle, the vicinal 3JHN

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

• of them, one of the C2' atoms of the adamantane substituent is located approximately in plane with the heterocyclic moiety of the compound. The populations of the two conformational forms in the single crystals of 15a and 15b (4:1 and 17:3, respectively) differ from the populations of the conformers

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

• initial 6–9 geometries corresponded to rotation along major degrees of freedom, i.e., C4’–C9 and C9–C8 bonds and orientation of the pendant ring. Conformers of up to 3 kcal/mol higher in energy were considered in the calculation and their contribution was included in the Boltzmann-weighted average

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• characteristic checkmark-shape, while the side chain conformation was not affected. The amide isomerism remained unchanged in polar aqueous medium. Conversely, in the nonpolar solvents, the equilibrium between the two conformers was shifted toward a more compact arrangement of the polar groups in the s-trans

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P^® activation of 3-arylpropiolic acids

• Melanie Denißen,
• Alexander Kraus,
• Guido J. Reiss and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 2340–2351, doi:10.3762/bjoc.13.231

• shoulder. This appearance might result from the free rotation of the N-phenyl substituents, furnishing emissive conformers that arise from a coplanar (λmax,em at 468.0 nm as a shoulder for compound 4a) and torsional orientation (λmax,em at 408.5 nm as a maximum for compound 4a) of the N-phenyl substituent

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• -trimethoxy derivative 45. In analogy to 1-methoxybuta-1,3-diene, 1-(dimethylamino)buta-1,3-diene was reacted with E- and Z-1b in CH2Cl2 at −50 °C yielding a single cycloadduct, which exists in equilibrium of two conformers as characterized by 1H NMR spectroscopy [46]. In the case of Z-1b, the initial

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• proline derivatives. The diastereoselective cyclization, which was clearly supported by DFT calculations is noteworthy. Further developments and applications of these scaffolds are currently underway. Optimized geometries for the two conformers presenting interactions with either Ca (16a) or Cb (16b). H

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

• phosphates). The 1H NMR analysis indicated that the helical property around the 1,2-diacyl moiety is considerably affected by these sn-3 substituents. The sn-3 hydroxy group induced a unique helical property, which was considerably dependent on the solvents used. In CDCl3 solution, three staggered conformers

• , 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

• ; deuterium labeling; sn-glycerol; glycerolipids; glycerophospholipids; helicity; Karplus equation; proton NMR spectroscopy; staggered conformers; Introduction Glycerophospholipids, constituting the basic elements of cytoplasm bilayer membranes, are responsible for several cell functions [1][2][3]. These

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

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

• conformational population and intramolecular interactions. The 3JH,H coupling constant has been widely used to estimate conformers population in an equilibrium [18], because of its dependence with the H–C–C–H dihedral angle, according to the Karplus curve. Chemical shifts can also be used, but they are more

• sensitive to solvent changes [27]. In the present study, the calculated H-1 and F-19 chemical shifts (Table 4) are too close for both conformers to differentiate them by comparing the absolute (calculated) and the mean experimental values. Also, the calculated long-range coupling constants 4JH,H are too

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• ). Unfortunately, we observed two signal sets in NMR spectra (intensity 3:1) for the product which could not be attributed to conformers or rotamers as evidenced by variable temperature and NOESY NMR experiments. These results, and the fact that Cochrane also reported problems due to epimerization during