From betaines to anionic N-heterocyclic carbenes. Borane, gold, rhodium, and nickel complexes starting from an imidazoliumphenolate and its carbene tautomer

• Ming Liu,
• Jan C. Namyslo,
• Martin Nieger,
• Mika Polamo and
• Andreas Schmidt

Beilstein J. Org. Chem. 2016, 12, 2673–2681, doi:10.3762/bjoc.12.264

• adduct displays two different conformers in the unit cell which differ inter alia in the torsion angles around the Nimidazole–Cphenol bonds [−53.32(16)° vs 114.12(13)°] and the Cphenyl–O bonds [49.43(17)° vs −15.29(18)°] (Figure 2). A gold complex of the N-heterocyclic carbene tautomer 6B can be obtained

• )), wR2 = 0.074 (all data), S = 1.04, largest diff. peak/hole = 0.359/−0.191 e Å−3. There are 2 different conformers in the asymmetric unit. 9: colorless crystals, C26H32AuN4O2∙0.19(Br)∙0.81(Cl), Mr = 673.42, crystal size 0.24 × 0.12 × 0.06 mm, monoclinic, space group C2/c (No. 15), a = 15.0275(9) Å, b

Biomimetic synthesis and HPLC–ECD analysis of the isomers of dracocephins A and B

• Viktor Ilkei,
• András Spaits,
• Anita Prechl,
• Áron Szigetvári,
• Zoltán Béni,
• Miklós Dékány,
• Csaba Szántay Jr,
• Judit Müller,
• Árpád Könczöl,
• Ádám Szappanos,
• Attila Mándi,
• Sándor Antus,
• Ana Martins,
• Attila Hunyadi,
• György Tibor Balogh,
• György Kalaus (†),
• Hedvig Bölcskei,
• László Hazai and
• Tibor Kurtán

Beilstein J. Org. Chem. 2016, 12, 2523–2534, doi:10.3762/bjoc.12.247

• column with the eluent hexane/2-propanol 80:20 (Supporting Information File 1, Figure S1). The initial conformational search of (R)-1 with the Merck Molecular Force Field (MMFF) and CHCl3 solvent model yielded 8 conformers within a 21 kJ/mol energy window, which were reoptimized at five different DFT

• levels [B3LYP/6-31G(d) in vacuo, B3LYP/TZVP PCM/CHCl3, B97D/TZVP [10][11] PCM/CHCl3, CAM-B3LYP/TZVP [12][13] PCM/CHCl3 and M06-2X/TZVP [14][15] PCM/CHCl3]. While the B3LYP and CAM-B3LYP functionals resulted in 4 low-energy conformers over 2% Boltzmann population with an equatorial C-2 aryl group near

• coplanar with the C-2– H-2 bond, the B97D and M06-2X ones afforded 8 conformers including four high-energy ones with an axial C-2 aryl group (Supporting Information File 1, Figures S2, S4, S6, and S8). The four CAM-B3LYP/TZVP (PCM/CHCl3) conformers (Figure 3) differed mostly in the orientation of the 7

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• Novel, functionalized piperazine derivatives were successfully synthesized and fully characterized by 1H/13C/19F NMR, MS, elemental analysis and lipophilicity. All piperazine compounds occur as conformers resulting from the partial amide double bond. Furthermore, a second conformational shape was

• , 49.0 ppm) are found when analyzing the 13C NMR spectra. Two effects are responsible for this behavior. The first arises from the presence of two different conformers (rotamers); this is caused by the limited interconversion by rotation about the C–N amide bond resulting from the partial double bond

• , interconversion of the amine is also reduced at room temperature. Normally, such formation of conformers is found for piperazines [21][22] and morpholines [21][23] only at lower temperatures (below −10 °C). Additionally, only the protons of 4-nitrobenzoylamides 3a, 4a and 5a exhibit this behavior at room

Experimental and theoretical investigations into the stability of cyclic aminals

• Edgar Sawatzky,
• Antonios Drakopoulos,
• Martin Rölz,
• Christoph Sotriffer,
• Bernd Engels and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 2280–2292, doi:10.3762/bjoc.12.221

• findings, minimum conformational energy calculations were conducted. We found that all compounds adhere to two groups of conformers in accordance with crystal structures reported in literature. Changing the minimum energy conformers of 9b and 13b,c into the reference structure 8a revealed an increase in

• diamine 2 and aldehyde 3 in basic or neutral media as well as for the protonated tetrahydroquinazoline 1’ and the corresponding diamine 2’ and aldehyde 3 in acidic media. Minimum energy conformers in their neutral form with (a) an axial orientation of the phenyl system exemplarily shown for compound 8a

New furoisocoumarins and isocoumarins from the mangrove endophytic fungus Aspergillus sp. 085242

• Ze’en Xiao,
• Senhua Chen,
• Runlin Cai,
• Shao’e Lin,
• Kui Hong and
• Zhigang She

Beilstein J. Org. Chem. 2016, 12, 2077–2085, doi:10.3762/bjoc.12.196

• program, respectively. Conformers within 10 kcal/mol energy window were generated and optimized using DFT calculations at B3LYP/6-31G(d) level. Conformers with Boltzmann distribution over 1% were chosen for ECD calculations in methanol at B3lYP/6-311+g(2d,p) level. The IEF-PCM solvent model for MeOH was

Thiophene-forming one-pot synthesis of three thienyl-bridged oligophenothiazines and their electronic properties

• Dominik Urselmann,
• Konstantin Deilhof,
• Bernhard Mayer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2016, 12, 2055–2064, doi:10.3762/bjoc.12.194

• proceeds with lower oxidation potentials and consistently reversible oxidations can be identified. The Stokes shifts are large and substantial fluorescence quantum yields can be measured. Computational chemistry indicates lowest energy conformers with sigmoidal and helical structure, similar to

• structures were confirmed by the absence of imaginary vibrations in the analytical frequency analyses. The inspection of the computed molecular structures 3 indicates that these molecules adopt sigmoidal and helical minimum conformers (Figure 4) as already shown for consanguineous series of higher

• and typical for many 3-(hetero)arylphenothiazines the Stokes shifts are large and substantial fluorescence quantum yields can be measured. Computational chemistry supports lowest-energy conformers with sigmoidal and helical structure, similar to oligophenothiazines. Furthermore, TD-DFT and even

Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

• Peng Zhang,
• Xiao-Ming Li,
• Xin-Xin Mao,
• Attila Mándi,
• Tibor Kurtán and
• Bin-Gui Wang

Beilstein J. Org. Chem. 2016, 12, 2012–2018, doi:10.3762/bjoc.12.188

• (Merck Molecular Force Field) level resulted in 55 conformers within a 21 kJ/mol energy window. These conformers were reoptimized at two different DFT levels, namely B3LYP/6-31G(d) in vacuo and B97D/TZVP [16][17] with a Polarizable Continuum Model (PCM) for MeCN [18]. The B3LYP optimization yielded 10

• low-energy conformers above 2% Boltzmann population, while the number of low-energy conformers was 14 at the applied B97D level (Figure 3). The conformers differed in the orientation of the methoxy groups and the value of the ωC12−C13−C3’−C9’ biaryl torsional angle resulting in different orientations

• of the C-13 indol and dihydro-5aH-[1]benzofuro [2,3-b]indole moieties. The different biaryl torsional angles produced markedly different computed ECD spectra for the conformers having M and P helicity such as the two lowest-energy computed B3LYP/6-31G(d) conformers (Figure 4). The two high-wavelength

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

• Lucie Brulíková,
• Aidan Harrison,
• Marvin J. Miller and
• Jan Hlaváč

Beilstein J. Org. Chem. 2016, 12, 1949–1980, doi:10.3762/bjoc.12.184

• authors explained this observation by a low-energy discrimination between the Panti and Psyn conformers of chiral diene 31e (Scheme 9) and by the high asynchronicity of the formation of the new bond with a nitroso partner (Panti and Psyn refers to the conformation of the O=P–C(1)–C(2) dihedral angles

Experimental and theoretical insights in the alkene–arene intramolecular π-stacking interaction

• Valeria Corne,
• Ariel M. Sarotti,
• Carmen Ramirez de Arellano,
• Rolando A. Spanevello and
• Alejandra G. Suárez

Beilstein J. Org. Chem. 2016, 12, 1616–1623, doi:10.3762/bjoc.12.158

• moieties lie parallel to each other, and the distances from the centroid of the aromatic ring to the midpoint of the C=C double bond are in the range of 3.25–3.31 Å, consistent with the distances for other π-stacked systems [2]. On the other hand, in the anti conformers the remoteness of the phenyl and

• conformational change can be responsible not only for the broadening of the NMR signals of some nuclei at room temperature, but also for the NMR splitting observed upon cooling. In the gauche conformers a significant shielding of the vinyl protons is expected, while in the anti rotamers those nuclei should not

• (6a), 95:5 (6b) and 91:9 (6c) in very good agreement with the average 9:1 value experimentally obtained from the low temperature NMR spectra. Moreover, the higher population of the π-stacked conformers found for 6a accounts for the magnitude of the shielding of the acrylate protons (Figure 2). In an

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• behaves as several conformers in solution (Figure 4). Indeed, the NOESY experiment shows correlations between the two protons in the ortho position (Ho and Ho’) of the phenyl ring and the H5 of the triazole. In this case, the position of the exocyclic amino group in meta position does not allow the

• formation of a strong H-bond and the C–C bond linking the triazole and the aromatic rings is free to rotate. To our surprise, a cross-peak between the H5 of the triazole and the H3’ was observed (as well as with the anomeric proton), indicating that both syn- and anti-conformers may be present. Enzyme

The hydrolysis of geminal ethers: a kinetic appraisal of orthoesters and ketals

• Sonia L. Repetto,
• James F. Costello,
• Craig P. Butts,
• Joseph K. W. Lam and
• Norman M. Ratcliffe

Beilstein J. Org. Chem. 2016, 12, 1467–1475, doi:10.3762/bjoc.12.143

• structures (see Experimental section). The half-chair (C2) arrangement was found to be the only stable conformer for the 1,3-dioxolane ring with all other conformers being rotamers about the C(2)–CH2R and C(2)–OMe bonds [where R = H (5) or t-Bu (16)]. The orientation of the C(2)O–Me group is ignored from

• projections of 9, 12 and 16 (viewed along Cβ→Cα). Newman projections [viewed Cα–C(2)] of the preferred C2 arrangement of the 1,3-dioxolane ring depicting the syn (16a,b), anti (16c) conformers, with (d) the superimposed calculated syn (16a = green) and anti (16c = red) structures viewed C(4)→C(5) [the C(2)O

• NOESY spectra (10/11/14), MS(CI) spectra (5*/16*), experimentally determined values of kH+ for the reacting mixtures of geminal ethers: [6 + 2], [3 + 2], [6 + 13], [6 + 5], [6 + 8], [6 + 10 + 11 + 14], [6 + 16], and Cartesian coordinates of conformers 16c. Supporting Information File 190: Analytical

Molecular weight control in organochromium olefin polymerization catalysis by hemilabile ligand–metal interactions

• Stefan Mark,
• Hubert Wadepohl and
• Markus Enders

Beilstein J. Org. Chem. 2016, 12, 1372–1379, doi:10.3762/bjoc.12.131

• absence of imaginary frequencies) where the functionalized side-arms interact with the metal center (complexes 3a+–8a+, see Figure 2, for the analogous complexes 1a+ and 2a+, respectively, no reasonable minima structures were obtained). We did not consider the conformers where the growing chain is on the

A modular approach to neutral P,N-ligands: synthesis and coordination chemistry

• Vladislav Vasilenko,
• Torsten Roth,
• Clemens K. Blasius,
• Sebastian N. Intorp,
• Hubert Wadepohl and
• Lutz H. Gade

Beilstein J. Org. Chem. 2016, 12, 846–853, doi:10.3762/bjoc.12.83

• throughout the reaction, the resulting mixtures do not require a purification step beyond a filtration from toluene or hexane to remove residual lithium chloride. As has been pointed out by Dyer et al. for the structurally related N-phosphanylamidines, there are several distinct conformers of ligands 2a–c

• temperature, indicating that a relatively fast interconversion of the different conformers occurs at ambient conditions. However, with increasing steric bulk of the aromatic nitrogen substituents, a substantial line broadening is observed, indicating the rise of the isomerization barrier through steric

Is conformation a fundamental descriptor in QSAR? A case for halogenated anesthetics

• Maria C. Guimarães,
• Mariene H. Duarte,
• Josué M. Silla and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2016, 12, 760–768, doi:10.3762/bjoc.12.76

• energies. These correspond to conformers 1, 2 and 3 of Table 1, the most stable ones in the gas phase and implicit solution. It is worth mentioning that, according to our calculations, the solvent has a little effect on the conformer populations, such as in enflurane [16], suggesting that intramolecular

• hyperconjugative interactions representing the anomeric effects (mainly LPO → σ*CF, Table 2), our natural bond orbital (NBO) analysis indicates that the main conformers 1 and 2 are less favored by electronic delocalization than 3, 4 and 5. Since the overall energy of a system is a composition of repulsive Lewis

• (only weak nonbonding interactions are observed for the high energy conformers 4 and 5). According to Koch and Popelier [19], the following QTAIM parameters, obtained by integration over the atomic basins of the hydrogen atoms participating in hydrogen bonds, should be observed to characterize hydrogen

cis–trans-Amide isomerism of the 3,4-dehydroproline residue, the ‘unpuckered’ proline

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2016, 12, 589–593, doi:10.3762/bjoc.12.57

• -trans and the s-cis conformational states (ca. 3–4 kJ/mol) [1][2]. In addition, the high energy barrier of the s-cis–s-trans isomerization (84–89 kJ/mol) stabilizes the amide conformers kinetically (Scheme 1) [3]. By comparison of the amide rotational rates of peptidyl-Pro with the ones of the closest

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

• ) conformers were sampled, both for the AMBER and the OPLS-AA force field, respectively. Both methods are capable to describe the overall flexibility of linezolid, particularly the orientation of the acetamidic side chain. In Figure 3 the lowest minima were superimposed and compared to the bioactive linezolid

• 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

• results comparing them with first principle DFT calculations. For both force fields the, 10 lowest conformers were used as a starting point for our DFT optimization in order to check if the same energetic order was achieved. The OPLS-AA force field produces an artifact: a global minimum, which is higher

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

• conformers of the homobisabolyl cation. In addition, conversion of the cedryl cation to the prezizyl cation involves the combination of two alkyl shift events into a concerted process that avoids formation of a secondary carbocation as a PES minimum (Figure 11, step 9, a “dyotropic” rearrangement) [102

• proceed without becoming “trapped” in an intermediate energy well. For some conformers of the bisabolyl cation, many trajectories proceeded to the cedryl cation without significant delay in the regions of the homobisabolyl and acorenyl cations. Subsequent automated docking calculations of carbocations

Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol

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

Beilstein J. Org. Chem. 2016, 12, 29–42, doi:10.3762/bjoc.12.5

• solution and illustrate their 3D structures. The most stable inclusion complexes conformers, presenting the weakest relative binding energies (ΔE) values, are illustrated in Figure 7. Firstly, results showed that 1 and 2 could form inclusion complexes with β-CD with the aromatic cycle embedded inside the

• entropic part of the inclusion phenomena is not simulated. In addition, the applied conformational research method showed that different conformers probably co-exist, since various structures with ΔE values quite close to those of the most stable conformers were obtained for both guests. On a structural

• point of view, these results are also consistent with the experimental NMR data showing that the most stable conformers for β-CD/1 and β-CD/2 resulted from a preferential inclusion mode; guests penetrate the CD via their methyl moiety and the isopropyl group of both is pointed to the secondary wider rim

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

• Agnieszka Hryniewicka,
• Szymon Suchodolski,
• Agnieszka Wojtkielewicz,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 2795–2804, doi:10.3762/bjoc.11.300

• moieties. Similarly, the C-2 protons give two singlets instead of one. We suspected that there is a hindered rotation on the N–C(chromenyl) bond, so that two conformers are observed by NMR. However, the 1H NMR spectrum recorded at elevated temperatures (30 and 50 °C) looked the same. In the 13C NMR

• spectrum, signals from some of the carbon atoms are doubled. The HSQC correlation confirms that the doubled signals derive from one carbon atom. This fact also may suggest that two conformers are observed in the NMR spectra. This issue will be the subject of future detailed investigations. Synthesis of the

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

• conformers in complex unit D is that the disordered components of the 17-OH group are separated by ≈1.5 Å, one as the major component (s.o.f. 0.61) and the other as the minor, with s.o.f. 0.39 and these –OH groups are donors in different guest–host hydrogen bonds. This feature is illustrated in Figure 7

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

• -labeled isotopomers of farnesyl diphosphate (FPP) [60]. These precursors were used to unambiguously assign both 13C NMR and (via HSQC) 1H NMR data of (1(10)E,4E)-germacradien-6-ol (34) from Streptomyces pratensis. The NMR spectra of this compound are complicated because of a mixture of conformers (Figure

• miltiradiene (33). Structure of the two interconvertible conformers of (1(10)E,4E)-germacradien-6-ol (34) studied with extensive 13C labeling experiments. a) Structure of rhizoxin (4). b) Two possible mechanisms of chain branching catalysed by a branching module. The 13C-labeled carbons are annotated with

Are D-manno-configured Amadori products ligands of the bacterial lectin FimH?

• Tobias-Elias Gloe,
• Insa Stamer,
• Cornelia Hojnik,
• Tanja M. Wrodnigg and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 1096–1104, doi:10.3762/bjoc.11.123

• gate that is formed by the side chains of Y48 and Y137 at the entrance of the CRD, has an open conformation. Prior to docking, energies of the Amadori ligands were minimised with the program MacroModel [25] and afterwards 23 different conformers of 9 and 20 conformers of 10, respectively, were

• generated with ConfGen [26][27] by using default settings. Next, these conformers were docked holding the FimH CRD fixed whereas conformational changes were allowed for the docked ligands under the influence of the force field. The resulting docking scores were calculated with the SP (single precision

• aniline to yield C-glycosyl-type D-mannoside derivatives 9 and 10, respectively. Docking scoring values of the most stable conformers complexed by FimH (open gate structure PDB 1KLF) of MeMan (1) in comparison with Amadori rearrangement products. Inhibition of bacterial adhesion (E. coli) to a mannan

On the strong difference in reactivity of acyclic and cyclic diazodiketones with thioketones: experimental results and quantum-chemical interpretation

• Andrey S. Mereshchenko,
• Alexey V. Ivanov,
• Viktor I. Baranovskii,
• Grzegorz Mloston,
• Ludmila L. Rodina and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2015, 11, 504–513, doi:10.3762/bjoc.11.57

• , Poland 10.3762/bjoc.11.57 Abstract The 1,3-dipolar cycloaddition of acyclic 2-diazo-1,3-dicarbonyl compounds (DDC) and thioketones preferably occurs with Z,E-conformers and leads to the formation of transient thiocarbonyl ylides in two stages. The thermodynamically favorable further transformation of C

• ,E-counterparts [26][27][28] (up to 4.7–5.0 kcal/mol). Because of this, calculations were carried out for the E,Z-conformers of acyclic 1a–d and the Z,Z-locked conformation of carbocyclic DDC 1e,f. The optimized structures of the E,Z-conformers for diazo compounds 1a–d are shown in Figure 2. The

• -dicarbonyl compounds with the C=S bonds of “superdipolarophilic” thioketones proceeds with Z,E-conformers of DDC via a concerted mechanism and adequately agree with experimental data. At room temperature, the 1,5-electrocyclization of the intermediate ylides into the 1,3-oxathiole derivatives is a

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

• , such as the bis-crown ether diamides 7 (Scheme 3), would possess similar structures with parallel substituents. Accordingly, we investigated the structures of compound 7a and 7b computationally. Again, there are several possible conformers of each compound, but the lowest-energy conformers shown in

• clarity. The lowest-energy calculated structure of 4 (B3LYP/6-31G**; for other conformers and full details see Supporting Information File 1). Bond lengths are given in Å and angles in degrees. The interchain 2 Å hydrogen bond is indicated by a dashed line. Calculated structure of 5 (B3LYP/6-31G**). Bond

Trogopterins A–C: Three new neolignans from feces of Trogopterus xanthipes

• Soyoon Baek,
• Xuikui Xia,
• Byung Sun Min,
• Chanil Park and
• Sang Hee Shim

Beilstein J. Org. Chem. 2014, 10, 2955–2962, doi:10.3762/bjoc.10.313

• model of this compound was created using MM2 with ChemDraw 3.0 (Figure 3). The resulting calculated interproton distances were in close agreement with the NOESY data (Table 3). A careful modeling study considering all the possible conformers of compound 3 exhibited that interproton distances between H-7