Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• both catalysts gave the Michael adduct in excellent yields, high ees were obtained only when 54b was used as organocatalyst (up to 94% ee, Scheme 16). During the last decade, squaramide catalysts have become a powerful alternative to the urea/thiourea and guanidine catalysts as multiple hydrogen bond

A three-armed cryptand with triazine and pyridine units: synthesis, structure and complexation with polycyclic aromatic compounds

• Claudia Lar,
• Adrian Woiczechowski-Pop,
• Attila Bende,
• Ioana Georgeta Grosu,
• Natalia Miklášová,
• Elena Bogdan,
• Niculina Daniela Hădade,
• Anamaria Terec and
• Ion Grosu

Beilstein J. Org. Chem. 2018, 14, 1370–1377, doi:10.3762/bjoc.14.115

• cryptand 2 they were 3.27 Å and 3.21 Å, respectively. Since the 3,5-dicyanopyridine fragment contains hydrogen-bond acceptor nitrogen atoms it might be possible to select a guest system which besides the stacking interaction could establish extra hydrogen bonds to enhance the complex stability. Accordingly

• , the O–H···N fragment did not preserve its hydrogen-bond arrangement, as the aromatic fragment rather preferred the so-called “antiparallel-displaced” configuration [40][41] (see Figure 6). The intermolecular interaction energy between 1,5-dihydroxynaphthalene and cryptand 2 is −29.28 kcal/mol, while

• -dihydroxynaphthalene. The higher affinity for anthracene and pyrene than for the dihydroxylated aromatic guest is explained by the influence of the polar solvent (DMSO). Molecular modelling revealed the preference for aryl–aryl stacking instead of a hydrogen bond between the donor OH groups of the guest and the

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• the vinca domain (Lys176, Val177 and Tyr210). Other than previously reported [52], the methoxy group of subunit B forms a hydrogen bond with Lys176 (Figure 2). Another binding mode of 2 with high binding affinity and hydrogen bond formation did not involve any interaction of subunit B, yet it was

• the other derivatives 23 and 24 (Figure 4). Besides hydrogen bond formation and binding affinity of inhibitors 2, 23 and 24, π-interactions and hydrophobic contacts with the binding pocket of the vinca domain were detected that would in turn increase the affinity of the inhibitor and its effect on the

• magenta. Docking of 22 to the vinca domain of β-tubulin. Surface and backbone of β-tubulin are shown in blue, GDP in yellow. No hydrogen bond formation was detected. The orientation of the azidoethoxy-ethoxyethyl substituent prevents the inhibitor from the correct interaction with the protein. The epoxide

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• substituent (3-quinolinyl nitrogen forming a hydrogen bond with a guanine amino group at the base of the minor groove) and a low pKa tail group. This drug was further selected for the treatment of Gram-positive bacteria Clostridium difficile infections and is currently in the phase II clinical trials

• selectively bind mixed G·C and A·T sequences of DNA. They hypothesized that thiophene (positive electrostatic potential) and the electron-donor nitrogen of N-MeBI should pre-organize the conformation for accepting hydrogen bond from G-NH2, which was validated by replacing the thiophene moiety with other

• ) were designed and synthesized by Dervan et al. and followed by other groups. It was observed that pyrrole/imidazole polyamides were able to bind side-by-side in the minor groove of DNA with high affinity and in a sequence-specific manner. Crystal structure studies confirmed the existence of a hydrogen

Correlation effects and many-body interactions in water clusters

• Andreas Heßelmann

Beilstein J. Org. Chem. 2018, 14, 979–991, doi:10.3762/bjoc.14.83

• explicitly or implicitly influenced by a water environment. An example for this is the hydrogen-bond cooperativity effect that can have a significant impact on the properties of the bare solute molecules [1]. In order to describe such phenomena, computer simulations have become an indispensable tool, since

Local energy decomposition analysis of hydrogen-bonded dimers within a domain-based pair natural orbital coupled cluster study

• Ahmet Altun,
• Frank Neese and
• Giovanni Bistoni

Beilstein J. Org. Chem. 2018, 14, 919–929, doi:10.3762/bjoc.14.79

• . This information is used to rationalize the trend of stability of various conformers of the water and hydrogen fluoride dimers. Keywords: DLPNO-CCSD(T); hydrogen-bond interaction; interaction energy; local energy decomposition; London dispersion; Introduction Hydrogen bonds are of fundamental

Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies

• Elias Christoforides,
• Andreas Papaioannou and
• Kostas Bethanis

Beilstein J. Org. Chem. 2018, 14, 838–848, doi:10.3762/bjoc.14.69

• numerous van der Waals and C–H···O interactions mainly between the guest and the inner dimeric host cavity. The observed host–guest interactions along with the extended hydrogen bond network between water molecules, hosts and guest are listed analytically in Supporting Information File 1, Table S1. In

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• malonate catalyzed by hydrogen-bond-donating organocatalysts (Scheme 2). We have also briefly investigated Meldrum´s acid as a donor, instead of dimethyl malonate, but we have obtained a complicated reaction mixture, which was difficult to purify. Therefore, we have focused our attention on the Michael

• synthesized binaphthol-squaramide catalysts (Sa,R,R)-C8, and (Sa,S,S)-C8 (Scheme 3). Results of the initial catalyst screening are summarized in Table 1. The binaphthyl structural motif has already been employed in the hydrogen-bond-donating organocatalysis [35][36]. However, the binaphthol moiety possessing

• an additional hydrogen bond donor group was not tested in too much depth. Therefore, we have synthesized two binaphthol-based diastereomeric squaramide catalysts (Sa,R,R)-C8 and (Sa,S,S)-C8 (Scheme 3). Starting from (S)-BINOL (8), amine 9 was obtained in five steps following literature procedures

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• moiety as monodentate hydrogen bond donor to activate the electrophile (anhydride), whilst retaining the tertiary amine functionality to activate the nucleophile (alcohol, Figure 2). As part of our ongoing research program on chloramphenicol base organocatalysis, herein, we report a new class of

• Lingjun Xu Shuwen Han Linjie Yan Haifeng Wang Haihui Peng Fener Chen Department of Chemistry, Fudan University, Shanghai 200433, PR China 10.3762/bjoc.14.19 Abstract A family of novel chloramphenicol base-amide organocatalysts possessing a NH functionality at C-1 position as monodentate hydrogen

• bond donor were developed and evaluated for enantioselective organocatalytic alcoholysis of meso-cyclic anhydrides. These structural diversified organocatalysts were found to induce high enantioselectivity in alcoholysis of anhydrides and was successfully applied to the asymmetric synthesis of (S

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• ) appending a fluorophore onto a natural nucleobase and (iii) the use of unnatural, intrinsically fluorescent nucleobases. They can be divided into fluorescent nucleobases capable of hydrogen bond formation, which can form specific base pairs with canonical nucleobases, and those that cannot (i.e., universal

• they will be non-responsive to the base pairing similar to PNA carrying tC or tCO [177]. Pyrrolocytosine is another intrinsically fluorescent hydrogen-bond-forming nucleobase that has been extensively studied in a DNA context [188][189]. When incorporated into PNA, the simple phenyl-substituted

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• C–F activation of benzylic fluorides for nucleophilic substitutions and Friedel–Crafts reactions, using a range of hydrogen bond donors such as water, triols or hexafluoroisopropanol (HFIP) as the activators. This study examines the stereointegrity of the C–F activation reaction through the use of

• demonstrated that both associative and dissociative pathways operate to varying degrees, according to the nature of the nucleophile and the hydrogen bond donor. Keywords: benzylic fluorides; C–F activation; chiral liquid crystal; 2H NMR; PBLG; stereochemistry; Introduction The C–F bond is the strongest

• ]. Protocols using water/isopropanol [3], optimally coordinated triols [4][5], and hexafluoroisopropanol (HFIP) [6][7] as the corresponding hydrogen bond donors have shown considerable success. This mode of activation has been demonstrated for amination [3][4][5] and Friedel–Crafts reactions [6][7] on benzylic

Polarization spectroscopy methods in the determination of interactions of small molecules with nucleic acids – tutorial

• Tamara Šmidlehner,
• Ivo Piantanida and
• Gennaro Pescitelli

Beilstein J. Org. Chem. 2018, 14, 84–105, doi:10.3762/bjoc.14.5

Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279

• -branched topology. The S3’ pocket in elastase is known to have a high aromatic specificity [74]. Interestingly, in our cases Phe in P3’ was less favored. Instead, mainly Lys occupied this position. Ala is favored in P2. Its carboxyl group can form a hydrogen bond with the amide nitrogen of Gly193 in the S2

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

• pentapeptide salts 1b–4b were obtained in quantitative yield. Conformational studies. The conformational properties of the eight pentapeptides (1a–4a and 1b–4b) were examined by NMR analyses in a protic solvent, which is more challenging than in aprotic organic solvents for maintaining intramolecular hydrogen

• bond network. Methanol was used because of the limited solubility of these compounds in aqueous solutions. The 1H and 13C chemical shifts of these pentapeptides were assigned using 1D 1H, 2D 1H,1H-TOCSY, 2D 1H,1H-ROESY, 2D 1H,13C-HSQC, and 2D 1H,13C-HMBC spectra. The 1H and 13C chemical shift

Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays

• Marco Russo,
• Daniele La Corte,
• Annalisa Pisciotta,
• Serena Riela,
• Rosa Alduina and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271

• binding between AmCD and Alg does not involve the host cavity, but implies a different mechanism, i.e., external electrostatic and hydrogen bond interactions. Therefore, it is not comparable with the interaction with p-nitroanilines. Moreover, it must be considered that the three AmCDs differ for both the

Binding abilities of a chiral calix[4]resorcinarene: a polarimetric investigation on a complex case of study

• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2698–2709, doi:10.3762/bjoc.13.268

• progressive deprotonation, and the consequent presence of an increasing negative charge, are reasonable. It is worth recalling here that the cone conformation of the resorcinarene scaffold is stabilized by the possible formation of a hydrogen-bond network between pairs of phenol groups on adjacent arene units

Ring-size-selective construction of fluorine-containing carbocycles via intramolecular iodoarylation of 1,1-difluoro-1-alkenes

• Takeshi Fujita,
• Ryo Kinoshita,
• Tsuyoshi Takanohashi,
• Naoto Suzuki and
• Junji Ichikawa

Beilstein J. Org. Chem. 2017, 13, 2682–2689, doi:10.3762/bjoc.13.266

• afford difluoromethylated dihydrophenanthrene derivative 4a in almost quantitative yield [29][30]. A difluoromethyl group functions as a hydrogen-bond donor and a bioisostere of a hydroxy group, as a result of which difluoromethyl-bearing compounds attract much attention as bioactive materials [31][32

Metal-mediated base pairs in parallel-stranded DNA

• Jens Müller

Beilstein J. Org. Chem. 2017, 13, 2671–2681, doi:10.3762/bjoc.13.265

• comprising one hydrogen bond only and in addition a destabilizing steric clash between two opposing amino groups (Scheme 1b). As a result, most reports on parallel-stranded DNA involving reversed Watson–Crick base pairs focus on A:T rich-sequences. The presence of interspersed G:C base pairs within a duplex

• [10][25]. A comparison of this cisoid base pair with its transoid counterpart (Scheme 4b) suggests that the latter geometry may be additionally stabilized by a synergistic hydrogen bond. Indeed, computations indicate that the transoid base pair is favoured by 7.6 kcal mol−1 in the gas phase [57]. It

• vs ΔTm = 5.5 °C) [62]. Even though this difference is not significant, it may be assumed that it is the result of one synergistic hydrogen bond, just like in the case of C–Ag(I)–C. In this study, the parallel-stranded alignment of the duplex was achieved by enforcing reversed Watson–Crick base pairs

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• located on the oxygen atom and the dipole moment of the amide bond is 3.6 D [7]. The amide bond can also perform hydrogen bonds, with the oxygen atom as the hydrogen bond acceptor and N–H as hydrogen bond donor. This characteristic is important for the formation of secondary structures and folding into

• negative charge, with a dipole moment of 1.4 D. Finally, the monofluoroalkene has the ability to accept a hydrogen bond through the fluorine atom [9]. Geometrically, the monofluoroalkene is quite similar to the amide bond. The C=O bond of the amide is 1.228 Å, compared to 1.376 Å for the C–F bond, and the

• obtain Tyr-Gly-Gly-ψ[(Z)-CF=CH]-Phe-Leu. The fluorinated Leu-enkephaline presented a 6-fold decreased binding affinity towards the DOPr receptor that the non-fluorinated analogue, showing that a hydrogen bond acceptor is necessary at this position of the peptide (Figure 6). The fluorinated peptide also

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• is the highly mannosylated glycoprotein uroplakin 1a (UPIa) [35][36]. The binding pocket of FimH accommodates a single α-D-mannose (1) with an extended hydrogen-bond network [37][38]. Accordingly, any modifications on the hydroxy groups of the mannose virtually abolish binding affinity [37][38][39

• Å2 for G, 262 Å2 for H, and 310 Å2 for I. The decreased dielectric constant ε in the deep cavities of H and I, as well as the resulting occlusion of the ligand from surrounding water molecules, leads to a more stable hydrogen-bond network and thus to higher affinities. Furthermore, the binding site

• calcium ions. During MD simulations, the number of ligand–protein hydrogen-bond interactions for lectins A–F varied from 1.5 to 3.5, and subsequently increased to 4.5 and 5.4 for LecB (G) and BC2L-A (H), respectively. Lastly, FimH (I) forms on average 7.9 hydrogen bonds with methyl α-D-mannopyranoside (2

Pyrene–nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies

• Artur Jabłoński,
• Yannic Fritz,
• Hans-Achim Wagenknecht,
• Rafał Czerwieniec,
• Tytus Bernaś,
• Damian Trzybiński,
• Krzysztof Woźniak and
• Konrad Kowalski

Beilstein J. Org. Chem. 2017, 13, 2521–2534, doi:10.3762/bjoc.13.249

• /C17/C18/O26 atoms and non-hydrogen atoms of the pyrenyl group are inclined by an angle of 17.26(5)°. The carbonyl oxygen atom O26 is involved in the intramolecular hydrogen bond with the hydrogen atom H3 of the pyrenyl group. The C3–H3···O26 hydrogen bond length is 2.879(2) Å. In the solid state, each

Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors

• Mukta Shaw,
• Yogesh Kumar,
• Rima Thakur and
• Amit Kumar

Beilstein J. Org. Chem. 2017, 13, 2385–2395, doi:10.3762/bjoc.13.236

• by the introduction of a cocatalyst such as an aryl thiourea derivative, which has the ability to form a dual hydrogen bond with the carboxylate and the alkoxy group of the ammonium salt [42][43][44]. To ensure our postulation, a 1H NMR spectroscopic study was carried out with a mixture of glycosyl

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• molecules (Figure 5b and Supporting Information File 1, section 7). Compound 5 may serve as a model for the crystal structure description. The molecules of 5 are linked by one C–H∙∙∙N hydrogen bond, so forming a dimer via eighteen-membered ring (e.g., see Figure 5c for 5) which can be described by graph-set

• notation as R22(18) [54]. Although the same motif formed by the analogous hydrogen bond is observed in other three structures (Table S3, Supporting Information File 1), the final supramolecular structures of 5–8 differ, from one-dimensional chains to three-dimensional network. It should be mentioned that

• gray. c) Capped-stick representation of 5, showing the dimer formed by C–H∙∙∙N hydrogen bond (orange stippled lines). Synthetic procedures for preparation of p-halogen-substituted and non-substituted phenyl-1,2,3-triazole 6-phenyl-2-(trifluoromethyl)quinolines. Reaction conditions and yields for the

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• yields. The X-ray analysis showed that products 53 obtained with primary amines are Z-configured whereas those derived from secondary amines, 54, display E-configuration [58] (Scheme 18). The observed different configurations demonstrate the importance of the intramolecular hydrogen-bond between the NH