The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• -regulation of Bim. Furthermore, the suggested interaction of mycolactone A/B with FKBP12 is supported by the protective effects of an excess of FK506 against mycolactone-induced apoptosis. However, further experimental validation of the mycolactone-FKBP12 interaction, e.g., by SPR, NMR or X-ray

• crystallography, would be highly appreciable. Finally, we also demonstrated the key role of mycolactone-triggered Bim-mediated apoptosis in vivo. To this end, the food pads of wild-type (WT) and homozygous Bim and Fas knockout mice (Bim−/− and Fas−/−) were infected with M. ulcerans. Intriguingly, WT and Fas

Molecular recognition of N-acetyltryptophan enantiomers by β-cyclodextrin

• Spyros D. Chatziefthimiou,
• Mario Inclán,
• Petros Giastas,
• Athanasios Papakyriakou,
• Konstantina Yannakopoulou and
• Irene M. Mavridis

Beilstein J. Org. Chem. 2017, 13, 1572–1582, doi:10.3762/bjoc.13.157

• constants, K, of the L- to the D-enantiomer) shows an increasing order (1.04, 1.1 and 1.34, respectively). X-ray crystallography, on the other hand, can improve our understanding of chiral recognition by CDs at the atomic level by providing insight into the interactions and the fit of the guest in the

• diagrams [15], NMR spectroscopy [16] and electrochemical methods [17], as well as by X-ray crystallography [18]. Detailed structures of β-CD with L- and D-N-acetylphenylalanine (NAcPhe) grown separately [18] has shown that although the two complexes are isomorphous (same space group, very similar unit cell

• percentage cannot be excluded. X-ray crystallography studies In the crystalline state, the structure of the inclusion complex of L-NAcTrp in β-CD comprises dimers. The asymmetric unit of the complex contains two crystallographically independent β-CD hosts (A and B) forming a dimer (Figure 2), in which two

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

• [1][28] but never isolated) was characterized by means of 1H and 13C NMR spectroscopy as well as X-ray crystallography. The isolation, for the first time, of the Mannich-type adduct 13 between HPA and an imine clearly attests to the viability of mechanistic pathway (b) shown in Scheme 3. When left at

• spectrometry and X-ray crystallography and certain regularities in the NMR behavior have been established, leading a set of rules for stereochemical assignment based on the NMR data. A Mannich-type adduct between HPA and an imine (previously only postulated as a crucial intermediate en route to CCR products

Nitration of 5,11-dihydroindolo[3,2-b]carbazoles and synthetic applications of their nitro-substituted derivatives

• Roman A. Irgashev,
• Nikita A. Kazin,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2017, 13, 1396–1406, doi:10.3762/bjoc.13.136

• nature of the target product and concomitant impurities. In addition to the data of 1H and 13C NMR and elemental analysis, the structure of nitro-substituted ICZs 9 and 10 has been confirmed unequivocally by X-ray crystallography analysis of derivatives 9b and 10b (Figure 4). Taking into account that

• performed by using the Suzuki–Miyaura cross-coupling reaction with phenylboronic acid under Pd catalysis (Scheme 5). The location of the formyl group and bromine atoms in ICZ derivatives 12 and 13 has been established by X-ray crystallography analysis, performed for single crystals of 12b and 13b (Figure 5

• desired product in 88% yield. At the same time, in the experiment with fuming nitric acid (5 equiv), used instead of acetyl nitrate (Table 1, entry 5), we have obtained a mixture of compound 2a and byproducts again. The molecular structure of compound 2a has been proved unequivocally by X-ray

Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• , anticancer, anti-HIV, antithrombotic, analgesic and antidiabetic [1][2][3]. Substitution on C(3) of quinoxalin-2(1H)-ones 1 by substituents that possess a carbonyl group in a β side chain position 2, 3 significantly alters their chemical properties as suggested by 1H NMR, IR spectra and X-ray crystallography

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• hydrolases; glycosyl transferases; kinetic crystallography; lectins; polysaccharides; powder diffraction; small-angle X-ray scattering; starch; synchrotron radiation; transporters; X-ray crystallography; Introduction Over the last decade, glycoscience has greatly benefited from the development of structural

• recognition with the elucidation of glycosyl hydrolases mechanism by X-ray crystallography, but the scope of applications in glycobiology is much broader: it encompasses the range of glycan containing (macro)-molecules and their conjugates. The present article reviews the application of synchrotron radiation

• thrombin and antithrombin at 2.5 Å resolution. For the time being, this is one of the largest oligosaccharide structures ever established throughout macromolecular X-ray crystallography (Figure 12) [59]. Transporters: Soluble sugars serve many purposes in complex organisms. Their cellular exchange relies

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• , so that the low number of structures being published represents the output of a major worldwide research effort to obtain structures for receptors that unfortunately require considerable ingenuity (and luck) to obtain suitable crystals for X-ray crystallography [6]. Not only has the paucity of

Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• 1H and 13C NMR spectra for final compounds. Supporting Information File 248: Crystallographic data. Acknowledgements The project described was supported by Award R35 GM118055 from the National Institute of General Medical Sciences. X-ray crystallography was performed by Dr. Peter White.

Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif

• Tetiana Bykova,
• Nawaf Al-Maharik,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2017, 13, 728–733, doi:10.3762/bjoc.13.72

• with Et3N·3HF at 120 °C generated the tetrafluorocyclohexane 11a, the structure of which was confirmed by X-ray crystallography (Scheme 2). Although the conversion of 10a to 11a was high as judged by 19F NMR, the isolated yield was modest as the compound was volatile and sublimed easily under reduced

• pressure. Hydrogenation of 11a over 10% Pd/C in ethyl acetate gave the desired amine 5a but in very low yield (0–15%) [18][19][20]. The structure of 5a was confirmed by X-ray crystallography (Scheme 2). Adding a few drops of formic acid and triethylamine (molar ratio 37:1) to the hydrogenation, furnished

• formamide 12 in 78% yield, a compound also confirmed by X-ray crystallography [20]. Ultimately treatment of nitrile 11a with nickel boride generated in situ from nickel chloride and sodium borohydride, resulted in its full reduction to amine 5a in 50% yield (Scheme 2) [21][22]. The analogous protocol was

Unpredictable cycloisomerization of 1,11-dien-6-ynes by a common cobalt catalyst

• Abdusalom A. Suleymanov,
• Dmitry V. Vasilyev,
• Valentin V. Novikov,
• Yulia V. Nelyubina and
• Dmitry S. Perekalin

Beilstein J. Org. Chem. 2017, 13, 639–643, doi:10.3762/bjoc.13.62

• diastereomer, however, it was not possible to unambiguously determine whether it was the cis- or the trans-isomer by NMR (including various correlation techniques) because of the high symmetry of both possible isomers. Attempts to grow crystals of 2c or its Br2 adduct for X-ray crystallography were also

• -spectrometry (for ethers, which are oils) or elemental analysis (for tosylamides, which are crystalline solids). The structures of the starting dienyne 1h and the cyclohexene trans-2b were established by X-ray crystallography. The structures of cis-2b and 3b had been reported previously [11][43]. Conclusion To

Highly bulky and stable geometry-constrained iminopyridines: Synthesis, structure and application in Pd-catalyzed Suzuki coupling of aryl chlorides

• Yi Lai,
• Zhijian Zong,
• Yujie Tang,
• Weimin Mo,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen,
• Liqun Jin,
• Wen-hua Sun and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 213–221, doi:10.3762/bjoc.13.24

• -ray crystallography were performed on a Bruker Smart Apex CCD area detector diffractometer using graphite-monochromated Mo Kα radiation (λ = 0.71073 Å). Details of the X-ray structure determinations and refinements are provided in Table 5. According to the synthetic procedures in the literature, the

• (30 m × 0.32 mm (i.d.), 0.25 μ). High-resolution mass spectra were recorded in the EI mode on Agilent 6210 TOF mass spectrometry. Flash column chromatography was performed on neutral SiO2 (200–300 mesh) with ethyl acetate/petroleum as eluent. Melting points were determined on BÜCHI M-565 apparatus. X

Supramolecular frameworks based on [60]fullerene hexakisadducts

• Andreas Kraft,
• Johannes Stangl,
• Ana-Maria Krause,
• Klaus Müller-Buschbaum and
• Florian Beuerle

Beilstein J. Org. Chem. 2017, 13, 1–9, doi:10.3762/bjoc.13.1

• . Experimental Hexakisadduct C3 [55] and malonate 1 [59] were synthesized according to literature procedures. X-ray crystallography: Bruker D8 Quest diffractometer with Photon 100 CMOS APS detector and Montel multilayer optics monochromated Cu Kα radiation. PXRD diffraction: Bruker D8 Discovery with 1D-Lynxeye

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• are used as reactive glycosyl donors in the syntheses of oligosaccharides. In addition, such heavy atom analogs of natural glycosides are useful tools for structure determination of their lectin receptors using X-ray crystallography. Some lectins, e.g., members of the tectonin family, only bind to

• -glucosamine, have been described in rats as metabolites for detoxifying inorganic selenite intake [12][13]. Selenium-containing compounds are also widely used as tools for protein X-ray crystallography in structural biology. The determination of a protein structure depends on the correct phase recovering

• mushroom Laccaria bicolor (Lb-Tec2) [28], a protein that belongs to the tectonin family of β-propeller lectins and plays an important role in fungal defense against bacteria and nematodes. The determination of the Lb-Tec2 structure by X-ray crystallography promised to be difficult since no suitable model

cis-Diastereoselective synthesis of chroman-fused tetralins as B-ring-modified analogues of brazilin

• Dimpee Gogoi,
• Runjun Devi,
• Pallab Pahari,
• Bipul Sarma and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2016, 12, 2816–2822, doi:10.3762/bjoc.12.280

• evidences for the structural assignment were sought from X-ray crystallography. Fortunately, we got the single crystals of (±)-5k by slow evaporation of a solution of 5k in hexane/EtOAc, and its molecular structure was confirmed by X-ray diffraction analysis (Figure 3). The 1H and 13C NMR spectra of all the

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

• to be known. Target information is usually obtained experimentally by X-ray crystallography or NMR (nuclear magnetic resonance). When neither is available, computational methods such as homology modeling may be used to predict the three-dimensional structures of targets. Knowing the structure makes

• 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

• , cryo-electron microscopy (cryoEM) has experienced a ‘resolution revolution’, leading to an increasing number of near-atomic resolution structures [18]. Experimental methods such as X-ray crystallography and NMR spectroscopy are associated with cost and time constraints, and are also limited by

Radical polymerization by a supramolecular catalyst: cyclodextrin with a RAFT reagent

• Kohei Koyanagi,
• Yoshinori Takashima,
• Takashi Nakamura,
• Hiroyasu Yamaguchi and
• Akira Harada

Beilstein J. Org. Chem. 2016, 12, 2495–2502, doi:10.3762/bjoc.12.244

• to studying the polymerization of vinyl monomers, we investigated the complex formation of CDs with vinyl monomers. When mixing α-CD and DMA, we obtained single crystals suitable for X-ray crystallography analysis. The X-ray crystallography analysis is important to understand the complex in the

• polymerization of water-soluble vinyl monomers using CD-CTA with molecular recognition property. α-CD was found to include a DMA monomer in a 1:1 manner, which was characterized using single X-ray crystallography analysis. The polymerization of DMA with α-CD-CTA resulted in poly(DMA) with a narrow distribution

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• stoichiometric coefficients in balanced chemical equations, as oxidation states of elements, as Miller indices and space groups in X-ray crystallography, as quantum numbers in atomic orbitals, as exponents in concentration terms in rate laws, as topological indices in knot theory applied to polymers, and as peak

New furoisocoumarins and isocoumarins from the mangrove endophytic fungus Aspergillus sp. 085242

• Ze’en Xiao,
• Senhua Chen,
• Runlin Cai,
• Shao’e Lin,
• Kui Hong and
• Zhigang She

Beilstein J. Org. Chem. 2016, 12, 2077–2085, doi:10.3762/bjoc.12.196

• accordance with the deduction from the X-ray crystallography analysis. Therefore, the structure of compound 2 was established as depicted in Figure 3 and named asperisocoumarin B. Asperisocoumarin C (3) was obtained as a pale yellow crystalline solid and displayed an [M + H]+ ion in HRESIMS at m/z 245.1174

• those reported in the literature as well as to the specific rotation. The structures of ustusorane B (7) and penicisochroman A (8) were analyzed by X-ray crystallography analysis (Figure 6) for the first time. Numerous isocoumarin and 3,4-dihydroisocoumarin derivatives have been isolated from various

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• isopropylation, and only around 40% of the starting material 13 was converted. Interestingly, the major product from the reaction was the O-iPr imine 15b as indicated by a low field 1H chemical shift of the isopropyl proton (5.39 ppm), and later confirmed by X-ray crystallography (the crystal structure is shown

• detector. Apodization = Happ General. Probe: Prob A DiComp (Diamond) connected via KAgX 9.5 mm × 2 m Fiber (Silver Halide); Sampling 2000–650 at 8 cm−1 resolution; Scan option: auto select, gain 1X. X-ray crystallography Single-crystal diffraction experiments were conducted on a Bruker APEX-II CCD

Synthesis and properties of fluorescent 4′-azulenyl-functionalized 2,2′:6′,2″-terpyridines

• Adrian E. Ion,
• Liliana Cristian,
• Mariana Voicescu,
• Masroor Bangesh,
• Augustin M. Madalan,
• Daniela Bala,
• Constantin Mihailciuc and
• Simona Nica

Beilstein J. Org. Chem. 2016, 12, 1812–1825, doi:10.3762/bjoc.12.171

• full-matrix least squares techniques based on F2 [46]. The non-H atoms were refined with anisotropic displacement parameters. Atomic scattering factors were taken from the international tables for X-ray crystallography. Hydrogen atoms were included but not refined. Calculations were performed using

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• potential binding sites have been described in the literature [17][18]. According to the X-ray crystallography, kinetics and mutagenesis studies, four effectors have been identified for binding in the effector site 1. The activation of the site 2 is more questionable as solid data is still required to

Stereodynamic tetrahydrobiisoindole “NU-BIPHEP(O)”s: functionalization, rotational barriers and non-covalent interactions

• Golo Storch,
• Sebastian Pallmann,
• Frank Rominger and
• Oliver Trapp

Beilstein J. Org. Chem. 2016, 12, 1453–1458, doi:10.3762/bjoc.12.141

• phase for seven days. Investigation of “NU-BIPHEP(O)” 1b. A) Solid-state structure determined by X-ray crystallography. Hydrogen atoms and methanol solvent molecules are omitted for clarity. B) Interaction studies in solution with soluble Okamoto phase 4 by 31P{1H} NMR spectroscopy. Black: spectrum of

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

• , bearing a phenyl group, the absorption of the CH2 group was found at 31.2 ppm. The structures of the ferrocenyl-substituted 1,3-dithiolanes 5b, 5e, 5f, and 5g have been established unambiguously by X-ray crystallography (see Figure 1 for 5b and 5f). The space group of 5b is non-centrosymmetric with a

Ring-whizzing in polyene-PtL₂ complexes revisited

• Oluwakemi A. Oloba-Whenu,
• Thomas A. Albright and
• Chirine Soubra-Ghaoui

Beilstein J. Org. Chem. 2016, 12, 1410–1420, doi:10.3762/bjoc.12.135

• the uncoordinated portion of the polyene having alternating C–C bond lengths of ≈1.45 and 1.35 Å. This is in fact the structure of an analogous Ni complex as determined by X-ray crystallography [56]. The haptotropic rearrangement of 28 to 30 does not permute all of the carbon atoms in the COT ring

Selective bromochlorination of a homoallylic alcohol for the total synthesis of (−)-anverene

• Frederick J. Seidl and
• Noah Z. Burns

Beilstein J. Org. Chem. 2016, 12, 1361–1365, doi:10.3762/bjoc.12.129

• (−)-anverene (1, see below), the absolute configuration of which was determined by the isolation chemists on natural material by X-ray crystallography [10]. Interestingly, using the same enantiomer of ligand, the bromochlorides derived from prenol and homoprenol (5) have the same absolute configuration. This