Terpenoids from Glechoma hederacea var. longituba and their biological activities

• Dong Hyun Kim,
• Song Lim Ham,
• Zahra Khan,
• Sun Yeou Kim,
• Sang Un Choi,
• Chung Sub Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2022, 18, 555–566, doi:10.3762/bjoc.18.58

• , H-3b/H-2b; H-6/H-3b/H3-15 suggested that H-6, H3-14, and H3-15 were positioned in the same orientation. To confirm the relative configuration of C-8 in 2 was determined using a DP4+ statistical analysis [13]. The DP4+ protocol was applied to the simulated 13C NMR chemical shifts of the conformer 2a

• based on the Boltzmann populations of each conformer in the associated Gibbs free energy (Supporting Information File 1, Figure S45). The ECD spectra were Boltzmann-weighted and generated using SpecDis software (Version 1.71) [23] with a σ/γ value of 0.30 eV. The chemical shift values were calculated

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• imidoacetal D. Due to free rotation of the (O,N,N)C–C(NO2) axis the suitable conformer E can be formed. Thus, the less hindered NH group of intermediate E interacts with the C3 position giving an intramolecular, five-membered addition product F. Upon elimination of HCl from F by means of the second equivalent

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• . Interestingly, the molecule does not bear any pseudo-mirror plane, that is, the observed conformer is asymmetric (C1) in itself, regardless the configuration of the two sulfinamide substituents. This peculiarity is likely due to the hindered rotation across the newly formed C–C bond, joining the two oxindole

• conformer. Aiming to generalize the discovered transformation, a brief scope of the reaction with respect to the N-tert-butanesulfinyl imine substrate was next performed (Figure 2). The protecting group R1 on the oxindole nitrogen atom was found to have a moderate effect on the reactivity, with R1 = Bn

• ) and one sulfinamide oxygen (O4). Atom numbering as in Figure 1. The asymmetry of such interactions reflects the intrinsic asymmetry of the solid-state conformer. Supporting Information Supporting Information File 42: Experimental part, NMR spectra and christallographic data of compound 2a.

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• high symmetrical geometry. Finally, a single broad peak for the four methoxy groups ($) appears at 2.96 ppm. In analogy with parental diureido and dithioureido calix[6]arenes, we were able to observe the presence of a second minor cone conformer, in a ≈4:1 ratio, highlighted by the presence of a second

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• ligand rotamers were considered during the optimization process. Only one enantiomer was selected for running the calculations for simplicity. The obtained results are gathered in Figure 1 and Figure 2. These calculations show that for ligands L1 and L3, conformer A and conformer B, resulting from a free

• nickel or palladium atoms. As far as the L1-Ni complex was concerned, this fluxional equilibrium disappeared due to metal coordination. In this case, complexes involving conformer B were highly energetic due to steric repulsion between the CO2Me substituents of the pyrrolidine ring. Thus, only one set of

• signals in NMR spectra (corresponding to conformer A) would be observed. For L1-Pd complexes, the aggregate included two energetically accessible rotamers at room temperature (energetic difference of +2.2 kcal·mol−1, Figure 1). Therefore, the duplicated set of signals in the 1H NMR was justified. We

Synthesis and investigation on optical and electrochemical properties of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 2450–2461, doi:10.3762/bjoc.17.162

• value, while the calculated LUMO energy was less negative. This can be explained by the fact that the calculations were achieved based on an equilibrium conformer. Conclusion In conclusion, we developed a convenient synthesis of novel 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines starting from

• a PGSTAT30 Autolab potentiostat. Theoretical calculations The theoretical studies were realized in vacuum with the Gaussian 09 program [70]. The geometry of the equilibrium conformer at the ground state was first found at AM1 level. Then, further optimization through density functional theory (DFT

Nomimicins B–D, new tetronate-class polyketides from a marine-derived actinomycete of the genus Actinomadura

• Zhiwei Zhang,
• Tao Zhou,
• Taehui Yang,
• Keisuke Fukaya,
• Enjuro Harunari,
• Shun Saito,
• Katsuhisa Yamada,
• Chiaki Imada,
• Daisuke Urabe and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2194–2202, doi:10.3762/bjoc.17.141

• Minimum (MCMM) method with PRCG energy minimization by the OPLS3e force field to obtain 56 conformational isomers within 10.0 kcal/mol from the minimum energy conformer. Geometries of the conformers were then optimized at the M06-2X/6-31G(d) level of theory with the SMD solvation model. Frequency

• of theory, affording 24 conformers within 3.0 kcal/mol from the minimum Gibbs free energy. The ECD spectrum of each conformer was simulated by the TDDFT calculation of 25 excited states at the ωB97X-D/def2-TZVP-PCM level of theory. The spectrum of structure 4a was created by the weighted average of

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli,
• Noureddine Chaaben,
• Kamel Alimi,
• Stefan Jopp and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 1629–1640, doi:10.3762/bjoc.17.115

• equilibrium conformer at ground state was first found at AM1 level. Then, further optimizations through density functional theory (DFT) approach [73] at the restricted Becke3–Lee–Yang–Parr hybrid functional (B3LYP) with standard basis set 6-31G were carried out. Experimental procedure and spectroscopic data

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• shift of the equilibrium between the [3 + 1] conformer, related to the shoulder at 255 nm [59], and the basket-type conformation of 22AG, assigned to the positive signal at 290 nm and the weak negative band at 260 nm [60][61] in favor of the latter. Hence, these observations showed that the ligands bind

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• -proliferative activity against tumor cell lines leading to the discovery of new lead compounds (Scheme 6). A tentative mechanism in Scheme 7 depicts the formation of iminium ion A from the reaction between 19 and 20 after the intramolecular protonation by carboxylic acid. The A conformer stabilized by

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• in the top five conformers (total population: 94.4%, data not shown, see below for detailed discussions). Although the characteristic NOESY crosspeak shown in Scheme 4 seemed to be attributable to the second conformer of the (2S)-isomer (29.4% population, data not shown), the other conformers were

• )-isomers 10 and 21, these three conditions match to define the stable conformer (see Figure 3 and Figure 8). However, the situation is different for the (S)-isomers 10* and 21* because there is no conformation that simultaneously fulfills these three conditions in these compounds. Thus, in 21*, to avoid a

• steric repulsion with the large ring C with the TFA group, the isopropyl group takes a conformation proximal to the methyl ester (see Figure 7). For 10*, with smaller size of the ring C, a conformer in which the isopropyl group and the methyl ester are separated also seems to be energetically

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• provides a higher stability to the trans-conformer, while the S-Flp increases the stability of the cis-amide. The relative stabilization is usually about 1–2 kJ⋅mol−1 when measured for the typical model compounds. Dfp exhibits a relatively weak destabilization of the trans-amide [16][52]. These energetic

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• of the product as a chair (1C4, 4C1) or a skew-boat (1S3, 3S1) conformer, of which the former is favored, as it proceeds via the lower-energetic chair-like transition state. The favored path of action will result in addition syn or anti to the substituent in position 5, depending on the starting

• conformer. Therefore, once the ground conformer of the oxocarbenium ion is established, this logic may be used to predict the reaction’s stereochemistry. The same principle may be successfully applied to reactions of iminium cations. We have previously shown that in the case of glucose- and galactose

Chiral anion recognition using calix[4]arene-based ureido receptors in a 1,3-alternate conformation

• Tereza Horáčková,
• Jan Budka,
• Vaclav Eigner,
• Wen-Sheng Chung,
• Petra Cuřínová and
• Pavel Lhoták

Beilstein J. Org. Chem. 2020, 16, 2999–3007, doi:10.3762/bjoc.16.249

• different conformations. Although the overwhelming majority of calixarene-based receptors makes use of the cone conformer A (Figure 1), the corresponding diureidocalix[4]arenes in the 1,3-alternate conformation B showed [42][43] surprisingly good complexation abilities towards selected anions. Especially

• for chiral anion recognition, contrary to the cone receptor, a design based on the 1,3-alternate conformer enables the introduction of chiral units into the phenolic functions of the inverted aromatic moieties nearby the ureido cavity responsible for the binding, as in C. This design can be

• exemplified by our previously published receptors C1 based on a calix[4]arene moiety or by C2 using thiacalix[4]arene as the core scaffold [44][45]. Moreover, the introduction of the tert-butyl groups into the 1,3-alternate conformer should lead to the overall increase rigidity of the molecule, possibly

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• 22AG that are formed in the K+-containing buffer solution [59]. In particular, the decrease of the positive shoulder around 270 nm shows the disappearance of the (3 + 1) conformer, to which this band is assigned [59], in favor of the basket-type antiparallel quadruplex structure, which is identified by

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• seem to dominate the conformer population distribution of 2 in chloroform solution, because the weight-averaged calculated J-values of 2a–c match the experimentally-measured J-values quite well (Figure 2). But none of the structures 2a–c are a close conformational match with piperine (1). A noteworthy

• approximate rotamers I and IV, respectively (Figure 1). The unexpectedly high relative energy that was calculated for compound 2f might be partially attributable to the fact that it features only a single F···H contact within 2.50 Å. The calculations suggest that the conformer 2f is not significantly

• this might increase the accessibility of conformer 2f. We reasoned that comparing the biological activities of 1 vs 2 might shed light on this possibility (vide infra). Photostability A limitation of piperine (1) as a drug lead is its instability under UV light. The conjugated system of 1 is well-known

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• the solution structures yields 5 clusters for the antigen and 4 clusters for the Tn-antigen (Figure 5A and B). The predominant conformer in both antigens is the extended form (Figure 5C), while for the Tn-antigen, the fourth cluster exhibits a more compact conformation (a transparent green conformer

• in Figure 5C) as noted in previous analysis. A cluster analysis of the bound antigens yields 5 clusters for the antigen and 4 clusters for the Tn-antigen (Figure 5D and E). The predominant conformer in both antigens is similar (Figure 5F), as noted in previous analysis. For the antigen, the first

Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction

• Daniela Rodrigues Silva,
• Joyce K. Daré and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2020, 16, 2469–2476, doi:10.3762/bjoc.16.200

• level of theory, ωB97X-D/6-311++G(d,p) [16][18], resulting in conformer Iag (Figure 2). This conformer has one fluorine atom in an anti-orientation and the other one in a gauche-orientation relative to the vicinal oxygen atom (pointing towards the amine hydrogen atom). To evaluate the other possible

• polar solvent (e.g. water), however, decreases the difference in energy among conformers and Igg becomes the most stable conformer in solution, i.e., a double gauche effect takes place (see data in parentheses in Figure 2). This is not surprising, since Igg has the highest dipole moment (data shown in

• conformational stabilities, we performed a numerical experiment in which the C–C(F) bond is rotated from conformer Iag keeping other geometrical parameters fixed. In this way, we can specifically investigate the intramolecular interactions governing conformational preferences in the 1,2–disubstituted ethane

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• modification, we have considered two biantennary systems, one terminating with β(1-2)-GlcNAc on both arms (ngf) and the other with terminal β(1-3)-Gal on both arms (gf), shown in Figure 1. In both glycoforms core α(1-3)-Fuc occupies a stable position, with one single conformer populated (100%), see Tables S1

• -3) arm is much more rigid relative to non-xylosylated species, see Table S3 in Supporting Information File 1, losing its “two conformer” dynamics characteristic of the biantennary mammalian N-glycans [24], also retained in the plant N-glycans with only α(1-3)-Fuc discussed above, see also Tables S1

• is able to form when in a 1C4 chair with the α(1-6)-Man, which may compensate for the steric compression, making the 1C4 chair the highest populated conformer at 76% within an N-glycan scaffold. Both experimental and ab-initio theoretical studies [36][37][38] have shown that the 1C4 chair is

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• for visualization. An equilibrium likely existed between two conformers where one complex had an additional hydrogen bond and the other included intramolecularly bonded lactate. For the lactate complexes with the larger receptors, whether one dominant conformer or a mixture of two conformers was

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• for the major amide rotamer in water, where the conformer was less defined. Overall, these outcomes demonstrate that the CF3 group favors an equatorial placement, but the preference is notably weaker as compared to the monofluoroprolines (Figure 5). It could be speculated that if the dipolar

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• conformer was identified for 23a and two for 23b (Figure 4). In the two preferred conformers of 23b (23b1 and 23b2), the plane of the ortho-formyl-substituted phenyl rings is twisted with 180° compared to each other. The Gibbs free energy difference between the two conformers is 4.1 kJ·mol−1 suggesting the

• possibility of a rotation of the ortho-formylphenyl group. Notably, conformer 23b1 is the more stable one, corresponding to the structure determined by solid-phase X-ray measurements (Figure 3, right). It should be mentioned that a few signals in the NMR spectra of 23b, e.g., δHC−N (5.71 dd), δHC= (131.1

• energy conformer of stereoisomer 23a and those of two minimal energy conformers of 23b (23b1 and 23b2) in DCM solution, based on DFT calculations. Rearrangement of methylenedioxy-substituted aminoaldehyde 1a to regioisomer 2a and formation of the dimer-like product 3a. Synthesis of 1-arylisoindoles 6 and

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• conformer. A quick geometry optimization (maximum number of iteration steps was set to 5) was then applied to refine the intermediates and discard the ones with high energy (energy cut off of 10 kcal·mol−1). Full geometry optimisation followed by the frequency and thermochemistry analysis was then performed

• initial guess due to particularly bad initial geometry – discard the conformer/intermediate, (iv) decomposed intermediate (no Pd–C bond determined by interatomic distance analysis) – discard intermediate. Literature validation In order to test the developed algorithm, a representative literature data

Synthesis and properties of quinazoline-based versatile exciplex-forming compounds

• Rasa Keruckiene,
• Simona Vekteryte,
• Ervinas Urbonas,
• Matas Guzauskas,
• Eigirdas Skuodis,
• Dmytro Volyniuk and
• Juozas V. Grazulevicius

Beilstein J. Org. Chem. 2020, 16, 1142–1153, doi:10.3762/bjoc.16.101

• with the Gaussian software [26]. Firstly, the equilibrium conformer search at the ground state was performed by using the MMFF (molecular mechanics force fields) method, and this geometry was used for further optimization. The vertical singlet and triplet energy values were calculated by using the

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• result was consistent with the observation of a set of ROESY correlations for H-3a/H-5'b, H-5/H-5'b, and H-2''/H-6'' in the most stable conformer of (2S)-isomer 1b, which were all incompatible with any conformers of the (2R)-isomer 1a (Figure 4). Furthermore, the (2S)-configuration was supported by the

• structures 1a and 1b The conformational search on structure 1a began by applying 100,000 steps of the Monte-Carlo Multiple Minimum (MCMM) method with PRCG energy minimization using the OPLS3e force field (gas phase) to obtain 20 conformational isomers within 5.0 kcal/mol from the minimum energy conformer