Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• Knoevenagel–[1,5]-hydride shift cyclization reaction of a 4-aryl-2-phenyl-1,4-benzoxazepine derivative obtained from flavanone. The relative configuration of products were determined by the correlation of 3JH,H coupling data with the geometry of major conformers accessed by DFT conformational analysis

• . Separated enantiomers of the products were characterized by HPLC-ECD data, which allowed their configurational assignment on the basis of TDDFT-ECD calculation of the solution conformers. Two compounds showed neuroprotective activities against hydrogen peroxide (H2O2) or β-amyloid25–35 (Aβ25–35)-induced

• same side of the molecules, the analysis of the computed solution conformers of cis-7a,b revealed that the orientation and distance (>4.6 Å) of these methine protons (Figure 3) does not allow for the detection of their NOE contact, rendering the NOE-based assignment of the relative configuration

Effect of cyclodextrin complexation on phenylpropanoids’ solubility and antioxidant activity

• Miriana Kfoury,
• David Landy,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2014, 10, 2322–2331, doi:10.3762/bjoc.10.241

• function of the solubility (log (S0)) of studied phenylpropanoids (red squares) and monoterpenoids (blue triangles) [32]. Representation of the most stable CD/trans-anethole inclusion complex conformers resulting from the two docking strategies. DPPH radical scavenging activity (%) of studied PPs alone or

• , CE, optimum molar ratio and increase in formulation bulk of phenylpropanoids. Supporting Information Supporting Information File 476: Phase solubility profiles of CD inclusion complexes and most stable CD/PP inclusion complex conformers. Acknowledgements Authors are grateful to Lebanese National

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• torsion angles between these groups (Table 2). Therefore, the anticipated configuration of the final products could be verified. Since compounds 6a and 8a were found to exist as complex mixtures of conformers, only anomeric signals were assigned. This finding is in agreement with the fact that ido

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• equilibrium of conformers. The output of the PSEUROT provides pseudorotation parameters: phase angles (P), the maximum puckering amplitudes (Φmax) and the relative amounts of individual conformers. The original PSEUROT program was later complemented with the program MULDER [11]. Recently, the Matlab

• analysis, it was necessary to assign correctly the NMR signals of the individual conformers. We noticed that only one of the C-2’ or C-5’ signals in the particular rotamer is split in the 13C NMR spectrum due to 3J(C,P) spin–spin interaction. In harmony with the general dependence of the vicinal coupling

• (C2’,P) in rotamer B should be observed. In order to support this assumption, we calculated 3J(C,P) of the most stable conformers (see the chapter Conformational analysis) of the adenine derivatives 13 and 14 for both A and B rotamers using the DFT B3LYP/6-31++G* method. The results summarized in

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• S3 in Supporting Information File 1). Taken together, these data suggest the population of two–three conformers and the experimental couplings are the average values of the corresponding vicinal atoms. It is noteworthy that the vicinal coupling constants H-1/F (9.95 Hz), H-3/F (24.39 Hz) and H-1/P

• atoms of the aforementioned phosphates, which can be assessed by comparing the partial positive charges of these carbon atoms. Indeed, the ab initio calculations yielded the following average values for the three most populated conformers of 2FAra-1P and Ara-1P 0.405 e and 0.434 e, respectively (Table 3

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• -mode conformational sampling method in MacroModel version 9.111. The resulting geometries were minimized with the Polak–Ribiere Conjugate Gradient algorithm with OPLS-2005 as a force field until convergence to a gradient of 0.05 kJ/mol. Redundant conformers were eliminated based on a rmsd cutoff of 0.5

Direct C–H trifluoromethylation of di- and trisubstituted alkenes by photoredox catalysis

• Ren Tomita,
• Yusuke Yasu,
• Takashi Koike and
• Munetaka Akita

Beilstein J. Org. Chem. 2014, 10, 1099–1106, doi:10.3762/bjoc.10.108

• -withdrawing CF3 substituent, provides trifluoromethylated alkene 3. Preferential formation of one isomer in the reaction of unsymmetrical substrates is attributed to the population of the rotational conformers of the β-CF3 carbocation intermediate 3+. Our experimental result is consistent with the previous

The Ugi four-component reaction as a concise modular synthetic tool for photo-induced electron transfer donor-anthraquinone dyads

• Sarah Bay,
• Gamall Makhloufi,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 1006–1016, doi:10.3762/bjoc.10.100

• probability for charge separation by photo-induced electron transfer based upon its Gibbs energy calculated from the analytical data and donor–acceptor distances of lowest energy conformers from inexpensive force field computations. Results and Discussion Synthesis and structure Within the concept of

Conformational analysis of 2,2-difluoroethylamine hydrochloride: double gauche effect

• Josué M. Silla,
• Claudimar J. Duarte,
• Rodrigo A. Cormanich,
• Roberto Rittner and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2014, 10, 877–882, doi:10.3762/bjoc.10.84

• through theoretical calculations and infrared spectroscopy [11]. No significant double gauche effect has been found in 1, since conformers possessing two fluorine atoms in the gauche relationship with the amino group (gauche-gauche, gg) are estimated to be similarly populated to those conformers with only

• perturbation analysis of donor-acceptor interactions in the natural bond orbitals (NBOs) framework shows that the global minimum of 1 is more stabilized by hyperconjugation than the other conformers (both in the gas phase and implicit water), despite being significantly destabilized by Lewis-type interactions

• comparison with these conformers in water −0.010 au and −0.009 au, respectively, indicate that F···HN+ hydrogen bonds are stronger in the gas phase than in water from the NCI point of view. Since two interactions of this type are present in gg against only one in ag, the gg conformer is expected to be more

Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• S2–S5) ascribable to solid state effects. The accuracy of the calculated NMR data is insufficient to distinguish between possible conformers of individual tautomers and so we did not performed a full conformational analysis. Conclusion Activated enol ethers 3 derived from trialkyl orthoformate and

Chromatographically separable rotamers of an unhindered amide

• Mario Geffe,
• Lars Andernach,
• Oliver Trapp and
• Till Opatz

Beilstein J. Org. Chem. 2014, 10, 701–706, doi:10.3762/bjoc.10.63

• ; Introduction The hindered rotation about the amide bond belongs to the most classical concepts taught to every undergraduate chemistry student. However, amide rotamers are generally classified as conformers which interconvert at ambient temperature unless a significant steric hindrance has to be overcome. This

• analysis. Computational studies The rotational barrier was also studied in silico. Therefore, a conformational analysis of 4 was performed using the systematic algorithm to search conformers as implemented in Spartan’10 with the semi-empirical PM6 level of theory [17][18]. All 2111 resulting conformers

Conformation of dehydropentapeptides containing four achiral amino acid residues – controlling the role of L-valine

• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Maciej Makowski,
• Rafał Latajka and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 660–666, doi:10.3762/bjoc.10.58

• investigated peptides were defined by using the XPLOR-NIH [32] program. The average values obtained for dihedral angles after the clustering of received conformers are presented in Table 3. In the case of peptides 1 and 2 the results of the calculations suggest that peptides could adopt two types of bent

• conformations, whereas for peptide 3 only one well-defined bent conformation could be found. Selected φ and ψ dihedral angles were excluded during clustering analysis for all investigated peptides. When we tried to group the obtained conformers according to all torsion angles of the main chain, the analysis did

• structural constraints were employed to calculate 1000 conformers by using the XPLOR-NIH [32] program. Structural preferences of the studied peptide were determined on the basis of 20% of the lowest energy conformers (200 conformers). Analysis of the obtained conformations and their clustering were done with

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• separated in the 13C NMR spectrum are, for instance, the ester carbonyl signals of the conformers (174.0 and 173.3 ppm), the carbonyl signals of the pyrrolidine amide (170.5 and 170.6 ppm), and all phenyl carbon signals. Of the eastern section, only three of the four pyrrolidine carbon signals are broad

• belonging to different signal sets are located at δH 3.84 (one of the diastereotopic OCH2 signals) and 5.21 ppm (acylated carbinol). The two sets of signals are probably caused by the presence of both conformers of the acyl pyrrolidine. An assignment of the data sets to either of the two conformers was not

• possible. The occurrence of conformers has been mentioned by Scheuer and co-workers and is also known for dolastatin 10 [12] and symplostatin 1 [13]. As an alternative route to the N-terminal tripeptide 11, we also investigated the coupling of the N-terminal dipeptide 15 with MMMAH tert-butyl ester (16

Decandrinin, an unprecedented C₉-spiro-fused 7,8-seco-ent-abietane from the Godavari mangrove Ceriops decandra

• Hui Wang,
• Min-Yi Li,
• Félix Zongwe Katele,
• Tirumani Satyanandamurty,
• Jun Wu and
• Gerhard Bringmann

Beilstein J. Org. Chem. 2014, 10, 276–281, doi:10.3762/bjoc.10.23

• calculations. The conformational analysis of 1 by using RI-SCS-MP2/def2-TZVP//B97D/TZVP yielded six relevant conformers within the energetical range of 3 kcal/mol above the global minimum. For each of the six conformers thus identified, TDB2PLYP/def2-TZVP calculations were performed providing single UV and CD

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• benzoylacrylic acid) – were investigated computationally. The geometrical structures of all possible conformers of the reacting systems were optimized using M06-2X [37] theory with the cc-pVTZ basis set [38] in the GAUSSIAN09 program [39]. The character of stationary points on the potential energy surface was

Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of ¹³C chemical shifts

• Simone Di Micco,
• Angela Zampella,
• Maria Valeria D’Auria,
• Carmen Festa,
• Simona De Marino,
• Raffaele Riccio,
• Craig P. Butts and
• Giuseppe Bifulco

Beilstein J. Org. Chem. 2013, 9, 2940–2949, doi:10.3762/bjoc.9.331

• due to equilibriums between multiple conformers, which are present in highly flexible molecules. Recently, the quantitative NOE-based method has been extended to relatively flexible compounds, and the reliability of the approach for the analysis of multiconformational systems was shown [19][20]. Due

• ). Over 200 conformers were found for each of the stereoisomers for 2a–h (see Experimental), and their geometries were optimized at the DFT theoretical level by using the MPW1PW91 functional and 6-31G(d) [26] basis set (Gaussian 09 Software Package [27]). From the DFT-optimized geometries interproton

• distances were calculated, accounting the Boltzmann-weighted average derived from the energies of the single conformers. For the analysis, we applied the previously described method [18][19][20][21], firstly recording different 1D NOESY spectra, irradiating at diverse resonances. In particular, the NOE

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• axial conformers are preferred by a substantial ~5.0 kcal/mol over the equatorial conformers (not shown) [28][29]. This pioneering work constituted the original discovery of the C–F…N+ interaction which has already been discussed above in the context of azetidines and pyrrolidines. Interestingly, Lankin

Synthesis and antibacterial activity of monocyclic 3-carboxamide tetramic acids

• Yong-Chul Jeong and
• Mark G. Moloney

Beilstein J. Org. Chem. 2013, 9, 1899–1906, doi:10.3762/bjoc.9.224

• ) tetramic acids (Figure 2) have been found to exist as a pair of external conformers (AB and CD) in slow equilibrium (ABCD), each consisting of a pair of internal tautomers in rapid equilibrium (AB and CD). The tautomerisation of 3-acyltetramic acids has been shown to be mainly affected by substitution on N

Thermochemistry and photochemistry of spiroketals derived from indan-2-one: Stepwise processes versus coarctate fragmentations

• Götz Bucher,
• Gernot Heitmann and
• Rainer Herges

Beilstein J. Org. Chem. 2013, 9, 1668–1676, doi:10.3762/bjoc.9.191

• pyrolysis products are as follows: [CO] = 13.5, [IN] = 9.1, [ET] = 15.4, [BC] = 19.4, [XY] = 1.2, [FA] = 12.2. Flash vacuum pyrolysis of indan-2-one cis-2-butene-1,4-diol ketal (3) again gave rise to a complex mixture of products (Figure 6). Among them, the two conformers of 1,3-butadiene (tBD and cBD

Mechanistic studies on the CAN-mediated intramolecular cyclization of δ-aryl-β-dicarbonyl compounds

• Brian M. Casey,
• Dhandapani V. Sadasivam and
• Robert A. Flowers II

Beilstein J. Org. Chem. 2013, 9, 1472–1479, doi:10.3762/bjoc.9.167

• obtain the minima. For the aryl diketone radical, two conformers for the ketones were considered, one with the carbonyl groups syn to each other and the other with the carbonyl groups in the anti orientation. For every substrate, two transition structures were identified on the energy surface along the

Dipolar addition to cyclic vinyl sulfones leading to dual conformation tricycles

• Steven S. Y. Wong,
• Michael G. Brant,
• Christopher Barr,
• Allen G. Oliver and
• Jeremy E. Wulff

Beilstein J. Org. Chem. 2013, 9, 1419–1425, doi:10.3762/bjoc.9.159

• 1H NMR signals below 330 K, with a coalescence temperature of approximately 280 K. At lower temperatures, two distinct conformations could be identified; by 213 K these were sufficiently well-resolved to permit integration (revealing a ≈7:1 ratio of the two conformers) and more extensive NMR analysis

• conformers, we calculated the 13C NMR shifts for our geometry-optimized structures, and compared these to the shifts obtained experimentally for the two conformations (Table 2). These agreed exceptionally well for those carbons not connected to the sulfone (relativistic effects were not well handled by our

• application in supramolecular or medicinal chemistry. DFT- and NMR-based studies agreed remarkably well in implicating the two interconverting species as the “endo” and “exo” conformers shown in Figure 2. Experimental General methods. Unless otherwise stated, all reagents were purchased from commercial

Establishing the concept of aza-[3 + 3] annulations using enones as a key expansion of this unified strategy in alkaloid synthesis

• Aleksey I. Gerasyuto,
• Zhi-Xiong Ma,
• Grant S. Buchanan and
• Richard P. Hsung

Beilstein J. Org. Chem. 2013, 9, 1170–1178, doi:10.3762/bjoc.9.131

• stable conformers and their corresponding energies are shown in Figure 3. To our surprise, propyleine (12) is 2.59 kcal mol−1 more stable than isopropyleine (14), which is the opposite of the Mueller–Thompson postulation [48]. Our calculations suggest that the ratio obtained from the Mueller–Thompson

Conformational analysis and intramolecular interactions in monosubstituted phenylboranes and phenylboronic acids

• Josué M. Silla,
• Rodrigo A. Cormanich,
• Roberto Rittner and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2013, 9, 1127–1134, doi:10.3762/bjoc.9.125

• corresponding conformers appreciably populated, because of steric effects and the loss of πCC→pB resonance. Thus, the results found earlier for 2-fluorophenol about the lack of intramolecular hydrogen bonding are now corroborated. Keywords: conformational analysis; hydrogen bond; interactions with boron

• analysis. The trans–cis form found elsewhere [24] was characterized here as a saddle point rather than a minimum (an imaginary frequency was found). Conformers 1a and 1b exhibit intramolecular hydrogen bonds, which is described in quantum terms as an nF→σ*OH interaction (example for 1a in Figure 3

• hydrogen bond, since the σOH is also oriented toward the fluorine substituent, giving rise to a repulsion (4-electron/2-orbital interaction). Thus, AIM calculations were performed to check for the predominant attractive interaction between F and OH rather than a repulsive one. Both 1a and 1b conformers

Tandem dinucleophilic cyclization of cyclohexane-1,3-diones with pyridinium salts

• Mostafa Kiamehr,
• Firouz Matloubi Moghaddam,
• Satenik Mkrtchyan,
• Volodymyr Semeniuchenko,
• Linda Supe,
• Alexander Villinger,
• Peter Langer and
• Viktor O. Iaroshenko

Beilstein J. Org. Chem. 2013, 9, 1119–1126, doi:10.3762/bjoc.9.124

• to be unimportant, because in both cases reactions run again through TS 22a (rate limiting), as was shown by additional computations. On the other hand, we have computed four conformers of TS 22: the conformation of the cyclohexane ring and that of the acetyl group were changed. While the cyclohexane

4-Pyridylnitrene and 2-pyrazinylcarbene

• Curt Wentrup,
• Ales Reisinger and
• David Kvaskoff

Beilstein J. Org. Chem. 2013, 9, 754–760, doi:10.3762/bjoc.9.85

• liquid N2 at −196 °C, or at 2092 cm−1 upon isolation in an Ar matrix at 10 K. The diazo compound is also formed on matrix photolysis of the triazole (Figure 1). Compound 22 can exist as s-Z and s-E conformers. One conformer dominates, absorbing strongly at 2092 cm−1; the other, minor absorption is at

• evolution of the azide photolysis reveals that the cyclic ketenimine 20 is formed first, followed by the open chain ketenimine 27 (Figure S3, Supporting Information File 1). It should be noted that ketenimine 27 can exist as four different s-E and s-Z conformers, with slightly different IR absorptions (the

• calculated spectra are shown in Figure 4 and Figure S6 and Figure S7, Supporting Information File 1). The experimental spectra indicate that all four conformers of 27 are formed, giving rise to bands at 2028–2060 cm−1, i.e., there is enough energy available to effect E–Z and s-E–s-Z isomerization in the