Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• compared to 9 (11% vs 8%), these values are sufficiently close to make any conclusions regarding the effects of conformational preferences on reactivity tenuous at best. However, it is interesting to note that the enantiomer of 11 has not been co-isolated as a natural product along with compounds (+)-1 and

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• . The conformational preferences of the stapled peptide P5 and of the linear peptides P6 and aAxWt were investigated via extensive accelerated molecular dynamics simulations (aMD) as implemented within the Amber18 program package [85]. The aMD methodology developed by McCammon and co-workers [86] has

• in Table S1 (Supporting Information File 1). The mutations from aAxWt to P6 result in a significant change in conformational preferences and the probability of stable β-structures in the latter. This observation is consistent with the CD spectrum of P6 that presents β-sheets features. The staple in

• frame and is coloured according to its corresponding re-weighted relative free energy. Data is calculated on the cumulative last 500 ns of 15 accelerated molecular dynamics runs for each SMC peptide. Molecular modelling of the conformational preferences of the SMC stapled peptides P5 (with cis or trans

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

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• estrogen receptor (ER) co-activator peptides and enabled the sensitive detection of their protein–peptide interaction inhibition by the ER antagonist tamoxifen [20]. Significantly, different secondary structure conformational preferences were also found among the diastereomers of perfluoro-tert

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

• identical φ–ψ distribution except that the peaks are slightly narrower for the Tn-antigen. In some cases, the preference stays the same and reduced flexibility is observed, for example, Pro2 (Figure S1 and S2 in Supporting Information File 1). In other cases, the conformational preferences shift on binding

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

• stereochemical effects of fluorination, responsible for specific interactions and conformational preferences of several groups of compounds, have become increasingly well understood [12], their direct implication on physicochemical properties has not been fully investigated yet. The orientation of fluorine

• 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

• term overcomes the stabilization from hyperconjugation interactions (ΔENL), and classical electrostatic and steric interactions are the main factors governing conformational preferences of penoxsulam (I). It is worth mentioning that the structure of penoxsulam in the biological environment is already

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

• these species, the methyl group does not introduce any new dipoles to the parent system, therefore only the conformational preferences should have an effect. Indeed, it was found that the cis-to-trans transition in 4-cis-methylproline (favors C4-exo) is faster compared to 4-trans-methylproline

• , acid–base transition, and kinetics of the amide-bond rotation. Interestingly it was found that the side-chain conformational preferences translate differently into the energy of the trans/cis amide equilibrium. While in the monofluoroprolines the effect was relatively strong, in the trifluoromethylated

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• ., in food industry and biomedicine. Keywords: antifreeze glycopeptides; conformational preferences; NMR; PP II; solid phase synthesis; Introduction Certain species of polar and sub-polar fish created evolutionary strategies to survive in water at temperatures below the colligative freezing point

• conformational preferences of the examined glycopeptides. Based on the NOESY/ROESY experiments we obtained 6, 27, 10 and 50 distance constrains for peptide 1, 2, 3, and 4, respectively (see Supporting Information File 1). For each of the investigated peptides optimization of 1 000 stable conformers have been

• acids should be much more flexible than analogues containing ᴅ-residues. Such observation is independent on the length of the peptide. In case of both tripeptides the performed calculations do not show any conformational preferences. Even regarding peptide 2, for which 27 interatomic distances have been

Conformational signature of Ishikawa´s reagent using NMR information from diastereotopic fluorines

• Laize A. F. Andrade,
• Lucas A. Zeoly,
• Rodrigo A. Cormanich and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2019, 15, 506–512, doi:10.3762/bjoc.15.44

• Ishikawa´s reagent [N,N-diethyl-(1,1,2,3,3,3-hexafluoropropyl)amine] is a fluorinating hexafluoropropylamine used to convert alcohols into alkyl fluorides. On the other hand, it is also an example of model compound useful to probe conformational preferences using spectroscopic information from

• incoming fluoride becomes magnetically more shielded than the fluorine not involved in such an interaction. Because the positioning of neighboring groups relative to the diastereotopic fluorines (NEt2 and CHFCF3 groups), the conformational preferences of Ishikawa´s reagent molecule may be influenced by the

Fluorocyclisation via I(I)/I(III) catalysis: a concise route to fluorinated oxazolines

• Felix Scheidt,
• Christian Thiehoff,
• Gülay Yilmaz,
• Stephanie Meyer,
• Constantin G. Daniliuc,
• Gerald Kehr and
• Ryan Gilmour

Beilstein J. Org. Chem. 2018, 14, 1021–1027, doi:10.3762/bjoc.14.88

• conformations around the two respective torsion angles [37][38]. In this case, it is also highly probable that hydrogen bonding will reinforce these conformational preferences. Whilst it was not possible to isolate crystals of 3 that were suitable for X-ray analysis, it was possible to unambiguously establish

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• peptide without the daunorubicin (Dau) part. This indicates that the main conformational preferences are not changed by the conjugation. The shapes of the ECD curves show a highly dynamic peptide structure in water. This is in agreement with the NMR study made by Pappa et al. that presented an extended

Conformational preferences of α-fluoroketones may influence their reactivity

• Graham Pattison

Beilstein J. Org. Chem. 2017, 13, 2915–2921, doi:10.3762/bjoc.13.284

• observed) (Scheme 2). Potential reasons behind the lower than expected reactivity of α-fluoroacetophenone were then considered. It is known that fluorine can dramatically influence the conformational preferences of molecules [8][9], so began by simulating the conformational energy profile of each α

• smaller dihedral angle preferred by the chlorinated derivative in the gas phase. Figure 3 compares the lowest energy conformations of α-fluoroacetophenone and α-chloroacetophenone in the polar solvent ethanol. Experimental work by Olivato amongst others supports these conformational preferences [11][12

• reactive conformations more accessible to the fluorinated acetophenone. Potential reasons for the different conformational preferences of the α-halogenated acetophenones were then examined. One possibility is that the increased electronegativity of fluorine induces a high dipole moment at small O=C–C–X

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

• proteins aggregation characterized by ordered β-sheet structure assemblies [14][15]. In this context, we synthesized and analyzed, by NMR and molecular modeling, the conformational preferences of eight pentapeptides, containing a L-serine, a L-threonine, a (2S,3R)-L-allo-CF3-threonine or a (2S,3S)-L-CF3

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

• nucleus. Fluorination of molecular scaffolds can also selectively influence a molecule’s polarity, conformational preferences and chemical reactivity, properties that can be exploited for various chemical applications. A powerful route for incorporating fluorine atoms in biomolecules is last-stage

Conformational study of L-methionine and L-cysteine derivatives through quantum chemical calculations and ³J_HH coupling constant analyses

• Weslley G. D. P. Silva,
• Carolyne B. Braga and
• Roberto Rittner

Beilstein J. Org. Chem. 2017, 13, 925–937, doi:10.3762/bjoc.13.94

• , according to the integral equation formalism polarizable continuum model (IEF−PCM), were obtained at the ωB97X-D/aug-cc-pVTZ level. The conformational preferences of the compounds in solution were also determined from experimental and theoretical 3JHH coupling constants analysis in different aprotic

• atoms in molecules (QTAIM) and noncovalent interactions (NCI) methodologies, the conformational preferences for the compounds are not dictated by intramolecular hydrogen bonding, but by a joint contribution of hyperconjugative and steric effects. Keywords: amino acid derivatives; conformational

• works presented unique explanations about the conformational preferences of amino acids. Therefore, it became of interest to extend the previous studies to investigate the conformational preferences of L-methionine and L-cysteine esterified and N-acetylated derivatives (Table 1). In order to obtain more

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• results on conformational preferences of 12 and 13 were corroborated using geometry-optimized density functional theory (DFT). The geometrically optimized preferred conformations of 12 and 13 are depicted in Figure 3, and geometrical parameters for torsion angles and intramolecular hydrogen bonding

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

• reasons. However, it has also been reported that N-acylated pyroglutamic acid exhibits almost exclusively the s-trans amide conformation despite being formally a 5-substituted Pro [22]. The conformational preferences of the heterocyclic analogues of proline [23][24][25] and, in particular, pseudoprolines

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

• Lenka Postova Slavetinska Dominik Rejman Radek Pohl Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic 10.3762/bjoc.10.205 Abstract Conformational preferences of the pyrrolidine ring in nucleotide analogs

Homochiral BINOL-based macrocycles with π-electron-rich, electron-withdrawing or extended spacing units as receptors for C₆₀

• Marco Caricato,
• Silvia Díez González,
• Idoia Arandia Ariño and
• Dario Pasini

Beilstein J. Org. Chem. 2014, 10, 1308–1316, doi:10.3762/bjoc.10.132

• selectivities of isolated products are unusual, considering that the [3 + 3] macrocycles are sometimes formed with similar synthetic efficiency as the [2 + 2] macrocycles (entries 2 and 3 in Table 1). It is very likely that those conformational preferences dominate in this context. The macrocycles were

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

• and Discussion The conformational isomerism of 2,2-difluoroethylamine (1) was computationally investigated at the MP2/6-311++g(d,p) level, both in the gas phase and implicit water (using the Polarizable Continuum Model). The conformational preferences are consistent with those obtained elsewhere

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

• carried out to determine the structures and the conformational preferences of the three dehydropentapeptides shown in Figure 1. NMR spectroscopy The combination of standard 1D and 2D NMR experiments, especially TOCSY, 1H,13C HSQC and 1H,13C HMBC, formed the basis of structural studies of the investigated

• resistant to the influence of the temperature and may create a weak hydrogen bond. While the results of the temperature experiments give important structural information, the most insightful data about the conformational preferences was obtained from 2D ROESY experiments. Based on the intensities of the

• determined on the basis of the vicinal coupling constants between the amide proton and the alpha proton [31]. Information about the number of structural constraints applied during calculation is summarized in Table 2. Based on the determined structural constraints, the conformational preferences of the

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

• azide group to align gauche to the ring nitrogen. The situation was not greatly changed upon introduction of a (6S)-fluorine atom (compound 22): in this case, no single conformation of 22 was able to satisfy a C–F…N+ gauche alignment as well as the two conformational preferences described for 21. In

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

• synthesis of a family of [3.3.0] bicyclic vinyl sulfones starting from 3-sulfolene [30], and their elaboration to inhibitors of viral neuraminidase (Scheme 1) [31]. Understanding the conformational preferences of the underlying bicyclic structure was crucial to the design and assembly of such inhibitors. In

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• S1–C3 bond. Such conformational preferences have been also observed for other sulfonamides and give rise to an optimal nN-σ*S,C interaction [31]. Further notable features are the interactions between the molecules in the crystal involving the sulfonamide nitrogen. Together with the hydrogen attached

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• differences on moving from DFT to MP2 single point energies is a rather general phenomenon observed in these studies. This implies that the definition of, for example, an energy window of 10 kJ/mol for conformational selection has different implications at these different levels of theory. Conformational

• preferences can, of course, also be quite different for the neutral Lewis base and its methyl cation adduct. For phosphane 120 we find that conformation 120Me_1 (Figure 16) has the lowest Etot on both levels of theory as well as the lowest H298. All calculated MCA values employ Boltzmann-averaging over all