Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• intermediate J values is consistent with two major conformations of 6a existing in equilibrium (Figure 2). The first conformer (left) has an extended zigzag structure. This matches the geometry that was observed in the X-ray crystal structure for the anti,syn-trifluoroalkane 40a [17]. The second conformer

• conformational averaging could be occurring about this bond. Overall, the pattern of large, small and intermediate J values is consistent with two conformations of 6b existing in equilibrium (Figure 2). The first conformer (left) has a bent structure. This provides gauche alignments between all pairs of vicinal

• C–F and C–N bonds, whilst avoiding 1,3-dipolar repulsion [11][12][43]. The second suggested conformer of 6b (right) has an extended zigzag structure. This geometry is counterintuitive, because although it provides gauche alignments between all pairs of vicinal C–F and C–N bonds, it includes an

Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by ¹H NMR spectroscopy

• Yoshihiro Nishida,
• Mengfei Yuan,
• Kazuo Fukuda,
• Kaito Fujisawa,
• Hirofumi Dohi and
• Hirotaka Uzawa

Beilstein J. Org. Chem. 2017, 13, 1999–2009, doi:10.3762/bjoc.13.196

• , namely gt(+), gg(−) and tg, were randomized, while in more polar solvents, the gt(+) conformer with (+)-helicity was amplified at the expense of gg(−) and tg conformers. The sn-3 phosphocholine in phosphatidylcholine exhibited a greater effect on the gt(+) conformer, which was independent of the solvents

• (+) and gg(−) conformations around the 1,2-diacyl moiety (Figure 1). From X-ray crystallography data, a common structure in which the 1,2-diacyl chains are aligned in parallel is observed, which adopts either the gt(+) or gg(−) conformer [7][10][12]. An analogous conformation has been reportedly observed

• conformational properties of a series of 1,2-dibenzoyl-sn-glycerols bearing different sn-3 substituting groups were examined. As shown in Figure 1, gt(+) is one of the gauche conformers with a right-handed (+)-helicity around 1,2-diol, while gg(−) is another gauche conformer with an antipodal left-handed

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

• José Enrique Barquera-Lozada and
• Gabriel Cuevas

Beilstein J. Org. Chem. 2017, 13, 1969–1976, doi:10.3762/bjoc.13.192

• elemanes formed via a Cope rearrangement from germacranolides only depends on the configuration of the most stable germacrane conformer since it is mainly a concerted reaction [15][18][33]. It is accepted that the conformers that normally carry out a Cope rearrangement are the ones that have crossed double

• coordinate of these four mechanisms. In the first proposed mechanism (path M, Figure 1) a conformational transformation of 1 must occur first. The most stable conformer has chair-boat conformation that according to Samek nomenclature is [15D5,1D14] (1a). This conformer is the one that is present in solution

• [37]. Nevertheless, conformer 1a does not have the proper geometry to directly generate the correct stereochemistry of 3. Both C–C bonds next to the C10–C1 double bond of conformer 1a have to rotate to generate the boat-boat conformer (1b, [15D5,1D14]), which is 3.5 kcal/mol less stable than 1a, but

Conformational impact of structural modifications in 2-fluorocyclohexanone

• Francisco A. Martins,
• Josué M. Silla and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2017, 13, 1781–1787, doi:10.3762/bjoc.13.172

• physicochemical/biological property of interest. In this work, structural changes in 2-fluorocyclohexanone were theoretically studied with the aim at finding intramolecular interactions that induce the conformational equilibrium towards the axial or equatorial conformer. The interactions evaluated were hydrogen

• gauche effect, but this did not appear, because of a predominant σC–H2 → π*C=O interaction in the equatorial conformer. The conformational induction through simple structural modifications can play an important role in the stereoselectivity of reactions (kinetically dependent on the conformation of the

• axial conformer. The axial conformer provides a gauche arrangement between the fluorine atom and the endocyclic group, while electron delocalization from electron donors, such as a σCH orbital to the vicinal π* orbital, as well as the spatial interaction between the fluorine substituent and the

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• attack on the least hindered face of a 1,2-chelated conformer (Figure 5C bottom, right). On the other hand, the minute formation of the 5’R-isomer that would be explained by the Felkin–Ahn model (Figure 5D bottom, left) is strongly disfavored due to the the bulkiness of the silyl groups hampering an

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• phenomenon could be rationalized by a different conformer population in the solution compared to solid state. This hypothesis was preliminary confirmed by the results of variable-temperature NMR experiments summarized in Supporting Information File 1 (Figures S1–S6). Another potentially useful criterion for

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• Ahlrichs’ basis set TZVP (triple zeta valence plus) polarization [30]. The number of excited states per each molecule was 24. The ECD spectra were generated by the program SpecDis [31] using a Gaussian band shape from dipole-length dipolar and rotational strengths. Equilibrium population of each conformer

• at 298.15 K was calculated from its relative free energies using Boltzmann statistics. The calculated spectra were generated from the low-energy conformers according to the Boltzmann weighting of each conformer in MeOH solution. For theoretical investigations on the photoinduced interconversion

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

• (NCI) analyses were used. Results and Discussion Esterified derivatives of L-Met and L-Cys The lowest-energy conformers of 1 and 2 and their calculated parameters (ωB97X-D/aug-cc-pVTZ) in gas phase and in solution (IEF−PCM) are shown in the Figure 1 and Table 2, respectively. Each conformer of 1 and 2

• investigated media. As well as for 1, geometries of 2 do not present significant variations when ε is increased. It also demonstrates that the solvent effect does not affect the conformer populations of 2. To obtain more details about the solvent effect in the conformational isomerism of the studied compounds

• on the dihedral angle H−C−C−H, according to the well-known Karplus relationship [25]. As the observed 3JHH,obs coupling constant represents a weighted average of the contribution of each conformer, the calculated 3JHH,calc spin−spin coupling constant represents the individual 3Ji coupling constant

The effect of cyclodextrin complexation on the solubility and photostability of nerolidol as pure compound and as main constituent of cabreuva essential oil

• Joyce Azzi,
• Pierre-Edouard Danjou,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2017, 13, 835–844, doi:10.3762/bjoc.13.84

• narrow side of CD. Molecular modelling The theoretical molecular modelling is useful to illustrate the most energetically favorable three-dimensional structure of the inclusion complex in solution. The inclusion complex conformer that presents the weakest relative binding energies (ΔE) (i.e., the most

• stable conformer) is represented in Figure 4b. The results showed that the formation of the β-CD/trans-Ner inclusion complex is an energetically favorable process and that the inclusion mode is coherent with the experimental NMR results. Photodegradation studies of Ner To the best of our knowledge, no

• diagrams of CD/trans-Ner inclusion complexes. Phase solubility profile of cabreuva EO obtained by the TOC method. a) 2D ROESY spectrum of β-CD/trans-Ner inclusion complex in D2O and b) representation of the most stable inclusion complex conformer. Photodegradation kinetics of cis-Ner (a), trans-Ner (b

Inclusion complexes of β-cyclodextrin with tricyclic drugs: an X-ray diffraction, NMR and molecular dynamics study

• Franca Castiglione,
• Fabio Ganazzoli,
• Luciana Malpezzi,
• Andrea Mele,
• Walter Panzeri and
• Giuseppina Raffaini

Beilstein J. Org. Chem. 2017, 13, 714–719, doi:10.3762/bjoc.13.70

• comparison of the X-ray structure and the MD simulations in water of 2/β-CD complex showed that 2 is present as single conformer in the crystal and in two conformations in the solution state. Materials and Methods X-ray diffraction Single crystals of 1/β-CD and 2/β-CD were obtained after many attempts by

Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study

• Michael L. McKee,
• Grzegorz Mlostoń,
• Katarzyna Urbaniak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 410–416, doi:10.3762/bjoc.13.44

• computational methods. The preferred formation of the unusual macroheterocycle, competitive with the 1,3-ring closure leading to a thiirane and the head-to-head dimerization yielding a 1,4-dithiane derivative, respectively, was explained based on the analysis of the structure of the favored conformer of the

• a 1.2 kcal/mol activation barrier (TS2) forming a C–C bond to give the intermediate, delocalized diradical 12 in a spontaneous reaction (∆G = −50.5 kcal/mol, Figure 3). This diradical can adopt a number of conformations. While the conformer surface was not fully explored, five conformers were

• density at the two corresponding C atoms and the strain required to reach the transition state. The spin densities of the two C atoms in conformer 12F, which is the precursor of the final product 9, is 0.25 e–, which is smaller than that of the two C atoms that do not form a new C–C bond (0.55 e−, Figure

Synthesis and optical properties of new 5'-aryl-substituted 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles

• Anastasia S. Kostyuchenko,
• Tatyana Yu. Zheleznova,
• Anton J. Stasyuk,
• Aleksandra Kurowska,
• Wojciech Domagala,
• Adam Pron and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2017, 13, 313–322, doi:10.3762/bjoc.13.34

• applied. Figure 3 shows a general representation of the compounds studied in this work. At the initial stage, a systematic conformational analysis of the series of substituted 1,3,4-oxadiazoles was conducted with the goal to determine the lowest-energy conformer(s). It has been found that 15c and 15d can

• exist only as a single conformer of planar structure. An increasing conformational variety has been observed for derivatives with substituents of increasing size. Thus, 15e can exist in two conformations with different orientation of the terminal substituents with respect to the central core. At the

• of 5'-aryl-substituted 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazoles 15b–g in DCM. Selected geometrical parameters (bond lengths, B and dihedral angles, D) for all found conformers of the studied compoundsa, as well as relative energies, Erel, for each conformer in the ground state obtained

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• also cause an enhancing effect by favoring conformational inversion to the stereoelectronically more stable conformer in the transition state. The reactivity of TBS-protected thioglycosides was further investigated by Scanlan and co-workers who made the fucosyl donor 34 (Scheme 6) [28]. Interestingly

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

• - and 4’-OH protons and the condensed hetero ring had M helicity with envelope conformation and C-2 pointing out of the plane (ωC-8a,O-1,C-2,C-3 = −51.6°, ωC-8a,C-4a,C-4,C-3 = 0.4° for the lowest-energy conformer). The C-2 aryl group was nearly coplanar with the C-2–H-2 bond and the ωH-2,C-2,C-1’,C-2

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

• second conformer). Radio-TLC (eluent: ethanol) of [18F]5b (Rf = 0.50; reaction mixture). (Radio)HPLC of 5a (tR = 7.7 min, UV trace, red), 5b (tR = 6.7 min, UV trace: blue) and [18F]5b (tR = 7.1 min, γ-trace, green). The differences in the retention times of 5b and [18F]5b occurs due to the setup of UV

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

• Felicia D’Andrea,
• Giorgio Catelani,
• Lorenzo Guazzelli and
• Venerando Pistarà

Beilstein J. Org. Chem. 2016, 12, 2343–2350, doi:10.3762/bjoc.12.227

• and 2.3 Hz) agree with four substituents in the equatorial position for the preferred conformer. A comparable example of intramolecular aldol condensation of a 1,5-dicarbonyl derivative has been reported by Tadano et al. [39]. Almost a sole aldol product was obtained in a good yield and was

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

• ’–c’), shared the same minimum energy conformer in which the phenyl ring in position 2 and the N-3 side group are in anti-axial orientation (exemplarily shown for compound 8a in Figure 7a) while the other compounds (neutral form: 8d,f, 9b,c; protonated form: 8f’, 9b’,c’) adhere to a conformer of

• : 177049 [46], 717617 [49], 778079 [50], 722943 [51], 820149 [52]; and for equatorial motif: 177050, 177052 [46]). Interestingly, the least stable compound 13b and the significantly more stable compound 8e were found to share the same anti-axial conformer in the neutral and in the N-3 protonated form

• using Molecular Mechanics (MM). For this purpose, the conformer of minimal energy for compounds 9b and 13b,c was kept frozen, while the N-side groups were changed into a methyl residue. The resulting structures were therefore identical with compound 8a, thus differences in potential energy are

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

• = 298 K). DFT-calculated minimum conformer of the 2,5-bis(terphenothiazinyl)thiophene 3c (calculated with the B3LYP functional and the 6-311G(d,p) basis set). Relevant Kohn–Sham FMOs contributing to the S1 states that are assigned to the longest wavelengths absorption bands of thienyl-bridged

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

• Cotton effects (CEs) had the same sign for conformer A and B, while the lower-wavelength (<250 nm) CEs were significantly different. The hindered rotation along the biaryl linkage may have implied an additional stereogenic element, which would have enabled atropodiastereomers with axial chirality. In

• order to explore the possibility of axial chirality, torsional angle scans were performed on the lowest-energy M (conformer A) and P (conformer B) helicity gas-phase conformers or atropodiastereomers. Rotational energy barriers between the two isomers were estimated to be ca. 35–42 kJ/mol for TS1 (ωC12

• compound 1. Structure and population of the low-energy B3LYP/6-31G(d) conformers (>2%) of (2R,3R)-1. Experimental ECD spectrum of 1 in MeCN compared with the computed PBE0/TZVP spectra of the lowest-energy M (ωC12−C13−C3’−C9’ = –46.1°, conformer A) and P (ωC12−C13−C3’−C9’ = 133.4°, conformer B) helicity

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

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

• approximately a 9:1 ratio, according to the relative area of the signals. Some authors have claimed that this effect could be due to a conformational equilibrium of s-cis and s-trans species that is shifted toward the s-trans conformer at lower temperatures [18][19][20][21]. Similar studies were carried out for

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

• ) ≈ 13:4. The antiperiplanar lone pair hypothesis (ALPH) proposes that the axial anomer of 4 constitutes the major conformer in solution [28], perhaps affording some stereoelectronic advantage to an early transition state which appears operative in the case of such acid-catalysed processes [29]. The

• 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

• enthalpy. No such flattened conformer exists for 5. The calculations are consistent with the model presented earlier in Figure 4. The increasing steric demand of substituent R [i.e., R = H (5); → Et (9); → iPr (12) → t-Bu (16)] leads to transannular clashing with axial C(3)/(4)–H atoms and subsequent

Unusual traits of cis and trans-2,3-dibromo-1,1-dimethylindane on the way from 1,1-dimethylindene to 2-bromo-, 3-bromo-, and 2,3-dibromo-1,1-dimethylindene

• Rudolf Knorr,
• David S. Stephenson,
• Ernst Lattke,
• Petra Böhrer and
• Jakob Ruhdorfer

Beilstein J. Org. Chem. 2016, 12, 1178–1184, doi:10.3762/bjoc.12.113

• conformer holds a pseudodiaxial, vicinal Br/H anti relationship and hence is (presumably) able to react somewhat faster. We abstained from separating trans-1 and cis-1 since the availability of two different mixtures facilitated the NMR assignments and because any cis-1/trans-1 mixture or the ensuing 3/4

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

• bonding is not a decisive interaction for the conformational equilibrium of isoflurane. Using a solvation model with explicit water, where specific solute–solvent interactions take place, conformer 1 is again the most stable form, suggesting that implicit solvation describes satisfactorily the actual

• differences in the Cl–C–O–C and C–O–C–H dihedral angles (±8° and 17°, respectively), the isoflurane structure bound to apoferritin (PDB code: 1XZ3 [9]) does not match any optimized conformer (Figure 1). So, does it make sense to use enzyme-free optimized conformations to obtain biochemical insights from 3D

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

• energy the 3,4-double bond increased the relative stability of the s-trans conformer by 0.2–0.3 kJ/mol, whereas the 4-CF3-group demonstrated an opposite effect of about 0.3 kJ/mol (standard error ±0.1 kJ/mol). Despite both effects being rather marginal, this indicates that the increase of the