Effective in silico prediction of new oxazolidinone antibiotics: force field simulations of the antibiotic–ribosome complex supervised by experiment and electronic structure methods

• Jörg Grunenberg and
• Giuseppe Licari

Beilstein J. Org. Chem. 2016, 12, 415–428, doi:10.3762/bjoc.12.45

• on the following assumption: in order to avoid an enthalpic penalty, the conformer of a drug-like molecule in the unbound state has to be similar to the bioactive conformational state. The result of our MC scans is shown in Figure 2. An overall number of ca. 450 low energy (40kJ/mol window

• plot for all sampled conformers shows that the AMBER force field produces a homogeneous distribution of the low energy conformations, while the OPLS-AA low-RMSD structures are clustered in confined areas with a 10 kJ/mol wide conformer gap between 25–35 kJ/mol. We finally evaluated our force fields

• intensified our scan at this point in order to make sure that we will not produce false positive hits for the linezolid analogues. An initial phase with 5000 steps produced a low energy conformer very similar to the conformation of linezolid in the crystal structure. After another 5000 steps (starting from

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• (specifically, those derived from the conformer of the bisabolyl cation that most readily formed the cedryl cation in the dynamics simulations) into the crystallographically-determined structure of epi-isozizaene synthase revealed that some carbocations along the reaction coordinate were bound more strongly

Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction

• Mino R. Caira,
• Susan A. Bourne,
• Halima Samsodien and
• Vincent J. Smith

Beilstein J. Org. Chem. 2015, 11, 2616–2630, doi:10.3762/bjoc.11.281

• present as two conformers in the ratio 0.61:0.39. One consequence of this is that there are two distinct positions for the O19–H phenolic group, each conformer forming a hydrogen bond with a different TRIMEB acceptor oxygen atom. Further details of this disorder and its implications are given below

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

•  8) that prevented a full assignment of NMR data by conventional methods. To correlate a conformational signal set, (U-13C15)FPP was synthesized and 13C,13C-COSY showed the connected carbon skeleton for each conformer. The 15 obtained labeled natural products also allowed a detailed analysis of the

Fe(II)/Et₃N-Relay-catalyzed domino reaction of isoxazoles with imidazolium salts in the synthesis of methyl 4-imidazolylpyrrole-2-carboxylates, its ylide and betaine derivatives

• Ekaterina E. Galenko,
• Olesya A. Tomashenko,
• Alexander F. Khlebnikov,
• Mikhail S. Novikov and
• Taras L. Panikorovskii

Beilstein J. Org. Chem. 2015, 11, 1732–1740, doi:10.3762/bjoc.11.189

• corresponding solvent at 298 K. Calculated data are based on the most stable conformer of 2−6. Supporting Information Supporting Information File 246: Detailed experimental procedures including characterization data for all synthesized compounds, 1H and 13C NMR spectra for all new compounds. Computational

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• Determining the structure of the thermodynamically stable product 4 proved to be more challenging. Our initial hypothesis was that it was an anomerically stabilised 8C5 conformer of 3 with the 6-methoxy group in the more stable equatorial position. Molecular mechanics calculations, however, showed that such a

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• cooling to 0 °C the IM/IEX ratio is increased to 100:30 (Figure 4, green curve) and at 77 K in a solid EPA [25] matrix the excimer emission completely disappears (Figure 4, blue curve). This behavior underlines the above-mentioned dynamic character of the excimer and suggests that the conformer 32a-STR is

Molecular cleft or tweezer compounds derived from trioxabicyclo[3.3.1]nonadiene diisocyanate and diacid dichloride

• Gert Kollenz,
• Ralf Smounig,
• Ferdinand Belaj,
• David Kvaskoff and
• Curt Wentrup

Beilstein J. Org. Chem. 2015, 11, 1–8, doi:10.3762/bjoc.11.1

• of 4 and 5 (see Figure S2 and Figure S3, Supporting Information File 1), the lowest-energy conformers shown in Figure 6 and Figure 7 are in very good agreement with the X-ray structures. The nearly parallel dangling chains in the lowest-energy conformer of 4 are particularly noteworthy (Figure 6). As

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

• compared with the computed ECD spectra of the gas-phase optimized conformers (>1%) of model compound (2S,15aS)-7d (1 conformer, B3LYP/TZVP) and (2S,15aS)-7b (2 conformers, BH&HLYP/TZVP). Bars represent the computed rotational strength values (R/8) of the lowest-energy conformer. c) Structure of the (2S

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

• interconverting conformer in solution, resulting in the observation of averaged experimental 3JHH. Nevertheless, even these averaged 3JHH can be used for conformational analysis by means of the program PSEUROT [10], which minimizes differences between experimental and calculated 3JHH, assuming a two-state

• pyrrolidine ring on its conformation. The conformation of phosphonomethyl derivatives 7 and 9 with trans configuration on 3’ and 4’ carbon atoms tends to occupy mainly (~60%) the 1T2 or 1E conformation in an equilibrium with the less populated (~40%) 1E conformer. This equilibrium is significantly shifted in

• hydrogen bonding between the 3’-OH group and the 4’-nucleobase substituent. A similar effect in the conformer populations was observed for phosphonoformyl derivatives. While trans derivatives 11 and 13 exist as an about 1:1 equilibrium mixture of 3T4 and 3T4 conformations, cis derivatives 12 and 14 prefer

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• of compound 3a in the crystal corresponds to the most stable conformer according to calculations at DFT B3LYP/6-31G(d) level in vacuo (ΔΔG298 K (equatorial/axial = 1.2 kcal/mol). One of the possible reasons for the higher stability of conformer 3a with a pseudo-axial methoxycarbonyl group in

• comparison to conformer 3a' with a pseudo-equatorial methoxycarbonyl group, is assumed to be the anomeric effect [24]. The lengthening of the C–CO2Me bond in conformer 3a compared to conformer 3a' (1.563/1.554 Å), corroborates this hypothesis. The pseudo-axia position of the methoxycarbonyl group is

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

• characterized by the closely related total energy (ET) values were found for the α-anomer 12a. The slightly more stable conformation (C-3-exo conformer; ET = −732311.2 kcal/mol) is stabilized by the intramolecular C-3OH···−OP (1.68 Å) hydrogen bond and the close proximity of the C-5OH hydrogen and FC-2 fluorine

• atoms (C-5OH···FC-2 1.98 Å). The other structure (C-3-exo conformer; ET = −732310.1 kcal/mol) does not contain the intramolecular hydrogen bonds. The torsion angles of the vicinal hydrogen atoms H-1/H-2 and H-2/H-3, the hydrogen–fluorine (H-1/F and H-3/F) and hydrogen–phosphorus (H-1/P), and the carbon

• the less stable conformer (ET = −732297.1 kcal/mol) with a twist 3T2 spatial structure of the pentofuranose ring is in accordance with the experimental coupling constant of 5.40 Hz, whereas those of H-1/H-2 and H-2/H-3 disagree with the relevant couplings (Figure 3; for detailed information, see Table

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• by compound 9a (Figure 2i). This phenomenon, already observed for N-substituted cyclic α-peptoid derivatives [35][36][37][38][39], indicated the presence of more than one conformer in slow exchange on the NMR time scale. It is well known that the conformational heterogeneity is due to tertiary amide

Substitution effect and effect of axle’s flexibility at (pseudo-)rotaxanes

• Friedrich Malberg,
• Jan Gerit Brandenburg,
• Werner Reckien,
• Oldamur Hollóczki,
• Stefan Grimme and
• Barbara Kirchner

Beilstein J. Org. Chem. 2014, 10, 1299–1307, doi:10.3762/bjoc.10.131

• for the understanding and the development of rotaxanes. Zerbetto et al. showed that the shuttling motion can be separated from the other degrees of freedom, and that the effective coordinate of the motion can be described as a double-minimum potential [18]. The co-conformer stability for rotaxane

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

• pairs resulting in four stacked (hetero)aromatic units (Figure 2), so that the anthraquinone moieties of two molecules display an average distance of ~3.8 Å. Based upon the X-ray data quantum mechanical computations on this conformer were envisioned (vide infra). Electronic properties and electronic

• dyad 1 an electronic prerequisite for electronically favored electron-transfer processes in donor–acceptor systems is the spatial proximity of PT and AQ. This conformer is additionally stabilized by π-stacking of the donor and the acceptor, which is adopted in the solid state and results in a strong

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

• one single fluorine gauche to the nitrogen atom (anti-gauche, ag) (Table 1). In fact, the most stable conformer of the neutral compound contains two fluorines gauche to the amino group, which presents both hydrogens directed toward fluorines, suggesting the formation of F···HN hydrogen bond. However

• . The conformational preference dramatically changes after protonation of 1 to give the 2,2-difluoroethylammonium cation (2), i.e. the conformer containing both fluorines gauche to the ammonium group (gg) is practically the single form in the equilibrium in the gas phase and, even in water solution

• , this conformer is calculated to amount to 90%. This preference is corroborated by NMR experiments (Supporting Information, File 1), because the measured 3JH,H and 3JH,F coupling constants (which have angular dependence according to the well known Karplus curve [12][13][14]) are consistent with the

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

• Information File 1, Tables S2–S5 and S14) but because of energy reasons the relative population of the C conformer must be vanishing in agreement with experimental data. This was confirmed by calculated NMR spectra (Supporting Information File 1, Table S15). Nevertheless, DFT data indicate a much lower

• proportion of the B conformer than implied by the experimental data. In contrast to the A tautomer, the B and C tautomers have planar >C–C–N–N–C–C< chains. X-ray and DFT optimized structures of the A tautomer exhibit significant differences in torsional angles only (see Supporting Information File 1, Tables

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

• conformer, a potential energy surface (PES) scan for the rotation around the C–N bond in steps of 10° was done. This scan provided two local minima as well as two maxima (Figure 5). The asymmetric peak shape is caused by the inversion of the pyramidal nitrogen between = 110° and = 120° as well as = 280

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• nitrogen N1, which is significantly shorter in 7a (2.194/2.110 Å respectively). The intramolecular hydrogen bond is probably also the cause for the occurrence of conformational isomers when inverting the configuration at C9. While catalyst (S)-4 solely exists as one conformer on the NMR timescale, its

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

• verified by calculations of vibrational frequencies within the harmonic approximation, using analytical second derivatives at the same level of theory. All stationary points possess zero imaginary frequencies. It was found that the acrylamide conformer I was more stable than conformer II by 1.24 kcal/mol

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

• contrast however, introduction of a (6R)-fluorine atom (compound 23) greatly rigidified the ring system, to the extent that a single conformer of 23 dominated in solution. This work highlights the subtleties that can arise when fluorine atoms are incorporated into highly flexible molecules with pre

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

• (HSQC, HMBC, ROESY, TOCSY and EXSY). The most significant difference between the NMR data for the two conformations was the substantial upfield shift for the two protons adjacent to the carbonyl (‘d’ in Figure 2) in the major conformer. This was consistent with this methylene group being substantially

• shielded by the electron-rich aromatic ring, as would be expected for the conformation observed in the X-ray structure (Figure 1). This upfield shift was not present in the minor conformer, suggesting that the pyrazolidinone ring had moved away from the aromatic ring’s magnetic influence. Analysis of

• the two lowest-energy structures shown in Figure 2A. Compellingly, the difference in ΔHf between these two structures (0.93 kcal/mol in favor of the exo conformer) agrees very well with the experimental difference in energy calculated from NMR integration of the two conformations at 213 K (0.8 kcal

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

• to evaluate the difference in affinity of boron towards oxygen and nitrogen electron pairs in 2-aminocarbonylphenylboronic acid (2-AC-PBA) and its corresponding ester, ethanediol(2-aminocarbonyl)phenylboronate (ED-2-AC-PB), that has been identified for some conformer interactions of type B–N and B–O

• 1a and 1b relative to 2a. Conformer 1c was found to be stabilized by a nonbonding F∙∙∙O interaction, which contributes to the formation of pseudo five-membered rings. This would be possible because of an nF→π*CC interaction (Figure 3), which contributes to a resonance structure with positive fluorine

• capable of interacting attractively with oxygen. Table 1 shows that the nF→π*CC interaction in 1c is ca. 3 kcal mol−1 stronger than in 1a and 1b, but not strong enough to make this conformer appreciably populated. Overall, 1a was calculated to be practically the only existing conformer, because of its

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

• 2092 cm−1 (major conformer) and 2076 cm−1 (minor conformer) (Figure 1): IR (Ar, 7 K) 795, 835, 918, 1009, 1056, 1150, 1299, 1434, 1476, 1574, 2076, 2092 cm−1. A small amount of the photoproduct 20 also appeared (1872 cm−1; Figure 1). Further photolysis afforded the product spectrum shown in Figure 2

Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids

• Paweł Borowiecki,
• Małgorzata Milner-Krawczyk and
• Jan Plenkiewicz

Beilstein J. Org. Chem. 2013, 9, 516–525, doi:10.3762/bjoc.9.56

• previously [58]. The absolute configuration of the substrate is deduced by interpretation of the signs of the ΔδRS values, by using an empirical model that assumes that in MPA esters of secondary alcohols, the most representative conformer has the methoxy group of MPA, the carbonyl group, and a proton bonded