Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• of glaucoma and was developed using structure-based tools (Figure 3) [7][8]. Protein structure determination All structure-based methods rely on the three-dimensional target structure. The most common way to determine a protein structure is by X-ray crystallography and NMR spectroscopy. Recently

• used in structure determination are mostly X-ray crystallography and NMR spectroscopy. As of 2016, the PDB databank contains around 120,000 biological macromolecular structures that have been deposited. It has structural information on over 20,000 bound ligand molecules as well. Swiss-Prot is a

• the target structure that are relevant to the biological function which are not accessible by experimental structure determination, can be obtained. The trajectories can be clustered to obtain a set of representative conformations. The difference here is that instead of using one structure, an

A direct method for the N-tetraalkylation of azamacrocycles

• Andrew J. Counsell,
• Angus T. Jones,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2016, 12, 2457–2461, doi:10.3762/bjoc.12.239

• via recrystallization or by passing the product through a short silica plug (see Table 1 and Supporting Information File 1 for details). Recrystallisation of 3 from a methanolic solution containing KClO4 yielded large, colourless, crystalline prisms. Single crystal X-ray structure determination

Potent triazine-based dehydrocondensing reagents substituted by an amido group

• Munetaka Kunishima,
• Daiki Kato,
• Nobu Kimura,
• Masanori Kitamura,
• Kohei Yamada and
• Kazuhito Hioki

Beilstein J. Org. Chem. 2016, 12, 1897–1903, doi:10.3762/bjoc.12.179

• ). Substrate scope of carboxylic acids 1 and amines 2. Supporting Information General information, synthesis of triazines I–X and structure determination, spectral data of amides 3, attempted synthesis of I from 6, amide-forming reaction with VI in the absence of NMM, and copies of 1H and 13C NMR spectra of

Methylpalladium complexes with pyrimidine-functionalized N-heterocyclic carbene ligands

• Dirk Meyer and
• Thomas Strassner

Beilstein J. Org. Chem. 2016, 12, 1557–1565, doi:10.3762/bjoc.12.150

• analysis. All energies reported are Gibbs free energies at standard conditions (T = 298 K, p = 1 atm) using unscaled frequencies. For visualization GaussView [75] was used. Solid-state structure determination of 9, 12 and 13 Preliminary examination and data collection were carried out on an area detecting

Synthesis of ferrocenyl-substituted 1,3-dithiolanes via [3 + 2]-cycloadditions of ferrocenyl hetaryl thioketones with thiocarbonyl S-methanides

• Grzegorz Mlostoń,
• Róża Hamera-Fałdyga,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 1421–1427, doi:10.3762/bjoc.12.136

• compounds 5 and 6, details of the crystal structure determination, and the original 1H and 13C NMR spectra for all products. Acknowledgements The authors thank the National Science Center (Cracow, Poland) for generous financial support (Grant Maestro–3 (Dec–2012/06/A/ST5/00219)). Skillful performance of

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

• 21% (3) to 81% (6). The ligand L3 as well as the pre-catalysts 4–8 were studied by single crystal X-ray analysis. A selection of molecular structures is presented in Figure 1 and details of the structure determination are presented in Table S1 (see Supporting Information File 1). Due to the rigid and

Synthesis of 2-oxindoles via 'transition-metal-free' intramolecular dehydrogenative coupling (IDC) of sp² C–H and sp³ C–H bonds

• Nivesh Kumar,
• Santanu Ghosh,
• Subhajit Bhunia and
• Alakesh Bisai

Beilstein J. Org. Chem. 2016, 12, 1153–1169, doi:10.3762/bjoc.12.111

• efficient one-pot formation of three consecutive carbon–carbon bonds. X-ray crystal structure determination of (±)-19b proved the outcome of the reaction unambiguously. It was noteworthy to observe Pd-catalyzed highly enantio-, chemo-, and diastereoselective double decarboxylative allylations on dimeric β-N

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• single X-ray crystal diffraction data of 14. Acknowledgements This work was supported by the EPSRC (Leadership Fellowship to D.J.D., Post-Doctoral Fellowship to P.J. and Doctoral Training Grant [EP/M50659X/1] to A.J.M.F.). We also thank Matt Rattley, Jinchao Yang for X-ray structure determination and

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• cysteine as a result of substrate incubation prior to crystallization. This was only possible with a very short substrate mimic which renders more similarity to the eastern chain. Using the longer western chain mimic no suitable crystals for structure determination could be produced (neither for CorB, nor

Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

• Jochen Kraft,
• Martin Golkowski and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 166–171, doi:10.3762/bjoc.12.18

• . The absolute configuration was assigned by comparison of the optical rotation values with literature data [29] which are based on the chemical correlation method leading to (+)-(S)-2-phenylsuccinate [30] and by X-ray structure determination of (R,E)-3,5-diphenylpent-4-enyl camphor-10-sulfonate [31

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

• least-squares technique using SHELXH [22]. With only a single complex unit DIMEB·2ME in the crystal asymmetric unit, structure solution was fairly straightforward. However, the structure determination and refinement of the TRIMEB inclusion complex proved to be considerably more challenging due to the

Bromotyrosine-derived alkaloids from the Caribbean sponge Aplysina lacunosa

• Qun Göthel,
• Thanchanok Sirirak and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2334–2342, doi:10.3762/bjoc.11.254

• ), 113.1 (C-2), 120.9 (C-4), 131.1 (C-5), 147.1 (C-3), 154.3 (C-8), and 159.0 (C-9) together with 1H,13C-HMBC correlations revealed that 2 consist of only one spirocyclohexadienylisoxazoline moiety in comparison with 1. The structure determination of 2 was accomplished based on 1H,1H-COSY and 1H,13C-HMBC

Hexacoordinate Ru-based olefin metathesis catalysts with pH-responsive N-heterocyclic carbene (NHC) and N-donor ligands for ROMP reactions in non-aqueous, aqueous and emulsion conditions

• Shawna L. Balof,
• K. Owen Nix,
• Matthew S. Olliff,
• Sarah E. Roessler,
• Arpita Saha,
• Kevin B. Müller,
• Ulrich Behrens,
• Edward J. Valente and
• Hans-Jörg Schanz

Beilstein J. Org. Chem. 2015, 11, 1960–1972, doi:10.3762/bjoc.11.212

• ; N, 12.41; found: C, 58.26; H, 6.49, N, 11.74. Crystal structure determination of complex 12. Crystals suitable for X-ray diffraction were obtained by layer diffusion of heptane into a THF solution of complex 12 at ambient temperatures over a period of 3 d to yield dark brown prisms. The crystals do

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• in the fusion of aromatic rings, which makes this assignment a difficult task. An initial solution for structure determination might be to associate a single crystal X-ray structure to the NMR data. Unfortunately, the development of a suitable crystal for the crystallographic analysis is not an easy

The chemical behavior of terminally tert-butylated polyolefins

• Dagmar Klein,
• Henning Hopf,
• Peter G. Jones,
• Ina Dix and
• Ralf Hänel

Beilstein J. Org. Chem. 2015, 11, 1246–1258, doi:10.3762/bjoc.11.139

• investigation was carried out. Although the quality of the structure determination was disappointing because of high residual electron density, it sufficed to determine the connectivity of the atoms in the compound and to demonstrate that the double bond configuration was E (Figure 1). The molecule possesses no

TTFs nonsymmetrically fused with alkylthiophenic moieties

• Rafaela A. L. Silva,
• Bruno J. C. Vieira,
• Marta M. Andrade,
• Isabel C. Santos,
• Sandra Rabaça,
• Dulce Belo and
• Manuel Almeida

Beilstein J. Org. Chem. 2015, 11, 628–637, doi:10.3762/bjoc.11.71

• electrolyte. Crystal structure determination X-ray diffraction studies were performed with a Bruker APEX-II CCD detector diffractometer using graphite-monochromated Mo Kα radiation (λ = 0.71073 Å), in the φ and ω scans mode. A semi empirical absorption correction was carried out using SADABS [25]. Data

Hetero-Diels–Alder reactions of hetaryl and aryl thioketones with acetylenic dienophiles

• Grzegorz Mlostoń,
• Paulina Grzelak,
• Maciej Mikina,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2015, 11, 576–582, doi:10.3762/bjoc.11.63

• sulfoxide. No attempts were made to isolate this product. The same oxidation protocol was applied to convert thiopyranes 5a, 4b, and 5b into the corresponding sulfones 6b–6d in 94, 70, and 80% yield, respectively. The structure of 6d was established by X-ray single crystal structure determination (Figure 2

• , details of the crystal structure determination, and the original 1H and 13C NMR spectra for all products. CCDC-1038599 and 1038600 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via http

• polycyclic thiopyran derivatives 4b and 4c, respectively, were obtained in 90 and 46% yield (Scheme 2). In the 1H NMR spectra of both compounds the low-field shifted CHS signal appeared at 5.82 and 4.49 ppm. Finally, the 2H-thiopyran structure of 4b was established by X-ray single crystal structure

Attempts to prepare an all-carbon indigoid system

• Şeref Yildizhan,
• Henning Hopf and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 363–372, doi:10.3762/bjoc.11.42

• not the hoped-for diene 22, but an isomer, the hydrocarbon 23 (Scheme 5). The structure of hydrocarbon 23 was established by the usual spectroscopic data (see experimental section) and also by an X-ray crystal structure determination (Figure 3). The molecule of 23 is planar (mean deviation 0.03 Å) and

• structure determination had to await X-ray crystallographic analysis. The required single crystals were obtained from the different chromatographic fractions (which contained either isomer in enriched form only) by recrystallization from chloroform and dichloromethane/chloroform, respectively. As can be

• observed (H5···π 2.76 Å, H9A···π 2.83 Å). The structure determination of 25 was of limited accuracy because of twinning and disorder problems (indeed, there may be a small amount of contamination by 24) and we therefore do not discuss it in detail. Both independent molecules display non-crystallographic

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• barriers. Supporting Information Supporting Information contains the experimental procedures, characterization of new compounds, copies of 1H, 13C and 31P NMR spectra, IR spectra, details of the X-ray structure determination, and details of the DFT calculations. Supporting Information File 189

Efficient deprotection of F-BODIPY derivatives: removal of BF₂ using Brønsted acids

• Mingfeng Yu,
• Joseph K.-H. Wong,
• Cyril Tang,
• Peter Turner,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 37–41, doi:10.3762/bjoc.11.6

• structure determination is available as Supporting Information File 2 and is also available on request from the Cambridge Crystallographic Data Centre as deposition 1018518. Conversion of F-BODIPYs 1 to the parent dipyrrins 2. Synthesis of the triazolyl-cyclam/F-BODIPY conjugates 3 (A) and 4 (B). Reagents

Inclusion of trans-resveratrol in methylated cyclodextrins: synthesis and solid-state structures

• Lee Trollope,
• Dyanne L. Cruickshank,
• Terence Noonan,
• Susan A. Bourne,
• Milena Sorrenti,
• Laura Catenacci and
• Mino R. Caira

Beilstein J. Org. Chem. 2014, 10, 3136–3151, doi:10.3762/bjoc.10.331

• , permethylated β-CD and 2,6-dimethylated β-CD) are described. Isolation of the corresponding crystalline 1:1 inclusion compounds enabled their full structure determination by X-ray analysis for the first time, revealing a variety of guest inclusion modes and unique supramolecular crystal packing motifs. The

Reversibly locked thionucleobase pairs in DNA to study base flipping enzymes

• Christine Beuck and
• Elmar Weinhold

Beilstein J. Org. Chem. 2014, 10, 2293–2306, doi:10.3762/bjoc.10.239

• , as we demonstrated for the DNA MTase M.TaqI, but could also be used to determine their site and mechanism of action by introducing cross-linked base pairs at different positions within the DNA, or stall proteins on the DNA in a pre-flipped complex for structure determination to reveal the initial

A new charge-tagged proline-based organocatalyst for mechanistic studies using electrospray mass spectrometry

• J. Alexander Willms,
• Rita Beel,
• Martin L. Schmidt,
• Christian Mundt and
• Marianne Engeser

Beilstein J. Org. Chem. 2014, 10, 2027–2037, doi:10.3762/bjoc.10.211

• to the reported procedure [54] and obtained as orange oil (using L-proline: 83%, using 1: 80%). Crystal structure determination: X-ray crystallographic analysis of 7 was performed on a Nonius KappaCCD diffractometer using graphite monochromated Mo Kα radiation (λ = 0.71073 Å). Intensities were

• X-ray structure determination and Prof. A. C. Filippou for providing X-ray infrastructure.

Five-membered ring annelation in [2.2]paracyclophanes by aldol condensation

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2014, 10, 2021–2026, doi:10.3762/bjoc.10.210

• were obtained by recrystallization from pentane/chloroform to allow their X-ray structure determination in the solid state. The results are shown in Figure 2. The molecule displays crystallographic inversion symmetry (which precludes the use of standard cyclophane numbering to some extent). It shows

Macrocyclic bis(ureas) as ligands for anion complexation

• Claudia Kretschmer,
• Gertrud Dittmann and
• Johannes Beck

Beilstein J. Org. Chem. 2014, 10, 1834–1839, doi:10.3762/bjoc.10.193

• planar ligand, as was shown by indole-based macrocycles [9]. This ligand system represents a stiff ring of two bis(indole) units connected via two ethynylene groups as linkers. As proven by a crystal structure determination, a chloride ion fits into the cavity bound via four N−H∙∙∙Cl bonds and strong

• in good yields. The quest for the molecular conformation is challenging for both molecules. Since the bis(triazenide) congeners of 1 and 2 are planar, one can presume an analogous molecular shape for the bis(ureas). All attempts to obtain single crystals of 1 for a structure determination failed