Synthesis and bioactivity of analogues of the marine antibiotic tropodithietic acid

• Patrick Rabe,
• Tim A. Klapschinski,
• Nelson L. Brock,
• Christian A. Citron,
• Paul D’Alvise,
• Lone Gram and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2014, 10, 1796–1801, doi:10.3762/bjoc.10.188

• . 297963, Becton, Dickinson and Company, Sparks, MD, USA). The minimum inhibitory concentration (MIC) of the compounds was determined using the microdilution method according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI 2006) [21]. All compounds were dissolved in DMSO to stock

Why a diaminopyrrolic tripodal receptor binds mannosides in acetonitrile but not in water?

• Diogo Vila-Viçosa,
• Oscar Francesconi and
• Miguel Machuqueiro

Beilstein J. Org. Chem. 2014, 10, 1513–1523, doi:10.3762/bjoc.10.156

• : conformational analysis; constant-pH MD; mannose; multivalent glycosystems; pH; synthetic receptor; Introduction The recognition of specific carbohydrates is an important step in several biological processes [1]. To better understand these recognition processes, several synthetic receptors have been developed

• ][18][19][20][21][22][23][24]. Since MD simulations deal with pH in a limited way, simply by setting a fixed protonation state in the beginning of the simulation, the use of one of these methods is mandatory. The stochastic titration constant-pH MD method [15][21] takes advantage from the

• complementarity between molecular mechanics/molecular dynamics (MM/MD) simulations, that correctly samples the conformational space of a system according to a classic potential energy function, and Poisson–Boltzmann/Monte Carlo methods, that can efficiently treat multiple protonation equilibria on rigid

New sesquiterpene hydroquinones from the Caribbean sponge Aka coralliphagum

• Qun Göthel and
• Matthias Köck

Beilstein J. Org. Chem. 2014, 10, 613–621, doi:10.3762/bjoc.10.52

• DAD detector (Jasco MD-2010 Plus). Accurate mass spectra were acquired using a Bruker micrOTOFLC mass spectrometer equipped with an ESI source. Mass calibration was performed using a sodium formate cluster prior each experiment. The sponges were collected by SCUBA diving at a depth of 29 m off the

Structure elucidation of β-cyclodextrin–xylazine complex by a combination of quantitative ¹H–¹H ROESY and molecular dynamics studies

• Syed Mashhood Ali,
• Kehkeshan Fatma and
• Snehal Dhokale

Beilstein J. Org. Chem. 2013, 9, 1917–1924, doi:10.3762/bjoc.9.226

• . Full ROESY spectrum of a β-CD-xylazine 1:1 mixture showing intermolecular crosspeaks. Two probable modes of the inclusion of xylazine into the β-CD cavity. Coordinate system used to define the complexation process. The time evolution of the potential energy calculated from the MD run in vacuum from (a

• ) wide side and (b) narrow side of β-CD cavity. Snapshots showing the inclusion of xylazine into the β-CD cavity as obtained in the MD trajectory from wide side. Snapshots showing the inclusion of xylazine into the β-CD cavity as obtained in the MD trajectory from narrow side. Side and front views of the

The β-cyclodextrin/benzene complex and its hydrogen bonds – a theoretical study using molecular dynamics, quantum mechanics and COSMO-RS

• Jutta Erika Helga Köhler and
• Nicole Grczelschak-Mick

Beilstein J. Org. Chem. 2013, 9, 118–134, doi:10.3762/bjoc.9.15

• investigated by three different theoretical methods: classical quantum mechanics (QM) on AM1 and on the BP/TZVP-DISP3 level of approximation, and thirdly by classical molecular dynamics simulations (MD) at different temperatures (120 K and 273 to 300 K). The hydrogen bonds at the larger O2/O3 rim of empty β

• its O6 rim than on its O2/O3 side when all hydrogen bonds were arranged in a concerted mode. This static QM picture of the β-CD/benzene complex at 0 K was extended by MD simulations. At 120 K benzene was mobile but always stayed inside the cavity of β-CD. The trajectories at 273, 280, 290 and 300 K

• simulations displayed different hydrogen bond patterns of cyclodextrins in crystal and in solution and confirmed the experimental findings of soluble cyclodextrin complexes of cholesterol type versus precipitates of cis/trans-cyclohexadecenone//CDs [10][11][12]. MD with λ-dynamics and calculation of the

Hydrophobic analogues of rhodamine B and rhodamine 101: potent fluorescent probes of mitochondria in living C. elegans

• Laurie F. Mottram,
• Safiyyah Forbes,
• Brian D. Ackley and
• Blake R. Peterson

Beilstein J. Org. Chem. 2012, 8, 2156–2165, doi:10.3762/bjoc.8.243

• . Fluorescence measurements employed either a PTi MD-5020 or a Perkin-Elmer LS55 fluorescence spectrometer with a 10 nm excitation slit width. 5-(Diethylamino)-2-{[4-(diethylamino)-2-hydroxyphenyl](2-methylphenyl)methyl}phenol (13): 3-Diethylaminophenol (11, 500 mg, 3.0 mmol) and o-tolualdehyde (12, 175 µL, 1.5

Multivalent display of the antimicrobial peptides BP100 and BP143

• Imma Güell,
• Rafael Ferre,
• Kasper K. Sørensen,
• Esther Badosa,
• Iteng Ng-Choi,
• Emilio Montesinos,
• Eduard Bardají,
• Lidia Feliu,
• Knud J. Jensen and
• Marta Planas

Beilstein J. Org. Chem. 2012, 8, 2106–2117, doi:10.3762/bjoc.8.237

• (Bruker Daltonics). High-resolution mass spectrometry (HRMS) was recorded on a Bruker MicroToF-Q MALDI instrument by using a hybrid quadrupole time-of-flight mass spectrometer (University of Zaragoza). Circular dichroism (CD) measurements were obtained using a Jasco spectropolarimeter (J-810, Easton, MD

Influence of intramolecular hydrogen bonds on the binding potential of methylated β-cyclodextrin derivatives

• Gerhard Wenz

Beilstein J. Org. Chem. 2012, 8, 1890–1895, doi:10.3762/bjoc.8.218

• bonds) between the secondary hydroxy groups of adjacent anhydroglucose units, as depicted in Figure 3 [38]. This finding was confirmed by MD calculations of CDs in the crystalline state and in aqueous environment [39][40]. A stabilization energy due to all O3H∙∙∙∙O2’ hydrogen bonds of 14 to 23 kJ mol−1

Peptides presenting the binding site of human CD4 for the HIV-1 envelope glycoprotein gp120

• Julia Meier,
• Kristin Kassler,
• Heinrich Sticht and
• Jutta Eichler

Beilstein J. Org. Chem. 2012, 8, 1858–1866, doi:10.3762/bjoc.8.214

• binding properties of CD4-M1 and CD4-M2, molecular dynamics (MD) simulations of the peptides in complex with gp120 were carried out and compared to a simulation of the CD4–gp120 complex. Analysis confirmed that the linear peptide CD4-M1 is more flexible than the respective region in CD4 (Figure 5A

• above. Absorbances (A) were read at 492 nm, and corrected for the respective blanks (wells without X5). All binding assays were performed at least twice, each time in duplicate. MD simulation Computational analysis included modelling of peptide–gp120 complexes followed by molecular dynamics simulation

• 22–64 were deleted to obtain the starting structure for the linear peptide CD4-M1. To obtain the complex for CD4-M2, mutations of S23C and D63C and the connecting disulfide bridge were additionally introduced by using Sybyl 7.3 [27]. Final system preparation and MD simulation were carried out

Partial thioamide scan on the lipopeptaibiotic trichogin GA IV. Effects on folding and bioactivity

• Marta De Zotti,
• Barbara Biondi,
• Cristina Peggion,
• Matteo De Poli,
• Haleh Fathi,
• Simona Oancea,
• Claudio Toniolo and
• Fernando Formaggio

Beilstein J. Org. Chem. 2012, 8, 1161–1171, doi:10.3762/bjoc.8.129

• -range connectivities, diagnostic of the presence of mixed 310-/α-helical conformations. The conformational properties of ψ[CS-NH]9 were further investigated by simulated annealing (SA) and restrained molecular dynamics (MD) calculations. A total of 69 interproton distance restraints, derived from the

• the 18 lowest energy structures are listed in Table S-I, Supporting Information File 1). Due to heavily overlapped ROE signals, the helical structures originated from the MD calculations appear not to superimpose perfectly in correspondence with the first three residues of the sequence. Even with this

• ± 2.9°) was detected at the C-terminus. In conclusion, the MD calculations based on the restraints derived from the ROESY spectrum of ψ[CS-NH]9 reveal the marked preference of this analogue for a mixed α-/310- helical conformation, with a clear α-helical character at the C-terminus on which the

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

Beilstein J. Org. Chem. 2012, 8, 915–929, doi:10.3762/bjoc.8.104

• adopt several conformations with different populations. The conformational space of a glycan can be analyzed by molecular dynamics (MD) simulations (see in the following) [100]. For this purpose the models generated by the GLYCAM Biomolecules Builder are convenient, as this tool already provides the

• synthetic glycan mimetics [117][118][119]. Results can be improved by combinations of different modeling approaches, such as docking and MD simulations [101]. To run reliable MD simulations of carbohydrate 3D structures, force fields are necessary that contain parameters for carbohydrates. In the case of

• for a long time [13]. With increasing computational power, MD simulations of larger molecules become feasible; and timescales of simulations increase. One major bottleneck for the scientific use of MD simulations that involve carbohydrates is, therefore, the availability of tools to analyze these

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• interference with the adhesion of melanoma (Figure 2) and endothelial cells (Figure 7) to the extracellular matrix protein. In order to investigate the molecular interactions of GSF in the RGD binding site of the integrin molecule in more detail we performed molecular dynamics (MD) simulation in explicit water

• . The MD simulation was started from the docked position of the GSF ligand. GSF slightly changed its position during the MD simulation, in which the sulfate group moved to the position that was occupied by the carboxylate group of the aspartic acid in the cyclic peptide (Figure 4C). The galactose forms

• several hydrogen bonds with the protein. A surface-water density analysis based on a MD simulation of the unligated protein in water revealed that the furan oxygen atom in GSF occupies the position of a (predicted) surface water-binding site. Impact of (4-{[(β-D-galactopyranosyl)oxy]methyl}furan-3-yl

Enantioselective supramolecular devices in the gas phase. Resorcin[4]arene as a model system

• Caterina Fraschetti,
• Matthias C. Letzel,
• Antonello Filippi,
• Maurizio Speranza and
• Jochen Mattay

Beilstein J. Org. Chem. 2012, 8, 539–550, doi:10.3762/bjoc.8.62

• reaction carried out in a nano ESI-FT-ICR instrument, supported by a thermodynamic MS-study and molecular-mechanics and molecular-dynamics (MM/MD) computational techniques. The noncovalent ion–molecule complexes are ideal for the study of chiral recognition in the absence of complicating solvent and

• well as in water: The skew-boat conformation of catharanthine is about 1 kcal mol−1 more stable than the chair conformation (Figure 5). The skew-boat structure of both T and TH+ is persistent during all the MD simulations, while the chair→skew-boat interconversion very easily occurs in aqueous TH

• structure may increase. According to the MM and MD calculations, both the [VS/R∙H∙T]+ enantiomers of the host tend to orientate two adjacent carbonyl oxygen atoms to the basic site of the guest. This arrangement requires that the structure of the host is strongly distorted from the uncomplexed form, by

(How) does 1,3,5-triethylbenzene scaffolding work? Analyzing the abilities of 1,3,5-triethylbenzene- and 1,3,5-trimethylbenzene-based scaffolds to preorganize the binding elements of supramolecular hosts and to improve binding of targets

• Xing Wang and
• Fraser Hof

Beilstein J. Org. Chem. 2012, 8, 1–10, doi:10.3762/bjoc.8.1

• period. Faced with evidence that the barriers to exchange of “up” and “down” conformers in the sterically congested 1,3,5-triethylbenzene and 1,3,5-trimethylbenzene systems are too high to examine conveniently by MD simulations, we turned instead to a calculation of the barriers to bond rotation for a

•  7. The calculated rotation barriers for ethyl directed hosts are in the same range as previously reported values for related systems, which were determined by variable temperature NMR to be 9.3–11.8 kcal/mol [6][20]. As with the MD simulations, these results indicate that both ethyl and methyl ortho

Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

• Celso Almeida,
• Stefan Kehraus,
• Miguel Prudêncio and
• Gabriele M. König

Beilstein J. Org. Chem. 2011, 7, 1636–1642, doi:10.3762/bjoc.7.192

• (University of Tromsø, MabCent, Tromsø, Norway); the Ki determinations and antagonist functional data that was generously provided by the National Institute of Mental Health's Psychoactive Drug Screening Program, Contract # HHSN-271-2008-00025-C (NIMH PDSP). The NIMH PDSP is directed by Bryan L. Roth MD, PhD

• at the University of North Carolina at Chapel Hill and Project Officer Jamie Driscol at NIMH, Bethesda MD, USA; we kindly thank also the remaining antiviral bioactivity tests performed by the U.S. National Institute of Health drug discovery program, which were supported by contracts NO1-A1-30048

Dependency of the regio- and stereoselectivity of intramolecular, ring-closing glycosylations upon the ring size

• Patrick Claude,
• Christian Lehmann and
• Thomas Ziegler

Beilstein J. Org. Chem. 2011, 7, 1609–1619, doi:10.3762/bjoc.7.189

• , justifying a more profound conformational analysis of this product (Figure 6). Conformational molecular dynamics runs (MD) were performed on both anomers of the two regioisomers of 8d to simulate the behavior of the molecule during more than 5000 ps of molecular motion. Thereby, it was found that for the

• observed regio- and stereochemistry an alternative conformation with two ASIs (2 + 2 ASI) and two intramolecular hydrogen bonds is significantly (2.2 kcal/mol) more stable than the virtual β(1→3)-linked product 6d; however, the triad-stabilized starting conformation for the MD is energetically

• significantly higher (4.8 kcal/mol) than the MD optimized conformation, since the latter profits from two hydrogen bonds and also two ASIs, even though it is decoupled. Thus, for the product constitution 8d with the highest relative macrocyclic ring constraint, the observed regio- and stereoselectivity can be

Evaluation of a commercial packed bed flow hydrogenator for reaction screening, optimization, and synthesis

• Marian C. Bryan,
• David Wernick,
• Christopher D. Hein,
• James V. Petersen,
• John W. Eschelbach and
• Elizabeth M. Doherty

Beilstein J. Org. Chem. 2011, 7, 1141–1149, doi:10.3762/bjoc.7.132

• Figure 1. The injector was a 6-port manual injector (Model C2-2006, Valco Instruments, Houston, TX) and the injection loop was obtained from Valco with a fixed volume of 2 mL. An LC-10A UV–vis detector (Shimadzu Corp., Columbia, MD) with a prep flow cell (0.1 mm path length) was connected downstream of

Catalysis: transition-state molecular recognition?

• Ian H. Williams

Beilstein J. Org. Chem. 2010, 6, 1026–1034, doi:10.3762/bjoc.6.117

• (PMF), computed from MD simulations at the AM1/CHARMM/TIP3P level with umbrella sampling along a reaction coordinate defined as the difference in bond lengths from Cα to the nucleophile and nucleofuge, predicted a 44 kJ mol−1 increase ΔG‡enz in free energy in going from the enzymic reactant complex

• exhibits no detectable enzyme activity [22], and so it is an intriguing question to investigate the nature of this OYHY…Oring interaction. MD simulations with the hybrid AM1/OPLS-AA/TIP3P method showed that both 4C1 chair and 2,5B boat conformers of phenyl β-xyloside remained stable in water during the

• course of 30 ps trajectories, even in the presence of propionate and propionic acid moieties to mimic Glu78 and Glu172 [23]. In contrast, analogous MD simulations for the 4C1 conformer of the reactant complex of phenyl β-xylobioside with BCX showed spontaneous transformation to the 2,5B conformer (Figure

EPR and pulsed ENDOR study of intermediates from reactions of aromatic azides with group 13 metal trichlorides

• Giorgio Bencivenni,
• Riccardo Cesari,
• Daniele Nanni,
• Hassane El Mkami and
• John C. Walton

Beilstein J. Org. Chem. 2010, 6, 713–725, doi:10.3762/bjoc.6.84

• packages. Pulsed EPR and ENDOR were performed using a pulsed EPR X-band spectrometer (Bruker Elexsys E580) equipped with a Dice-ENDOR accessory, a radio frequency (rf) amplifier and a dielectric-ring ENDOR resonator (Bruker EN4118X-MD-4-W1). Samples were maintained at 50 K using liquid helium in an Oxford

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• , temperature coefficient (Δδ/ΔT) measurements of amide protons and constrained MD simulations revealed that all the cyclic oligomers had symmetrical structures, although none of the unprotected cyclic oligomers displayed any ability to transport ions across model membranes according to ion flux studies. Cyclic

Ring strain and total syntheses of modified macrocycles of the isoplagiochin type

• Andreas Speicher,
• Timo Backes,
• Kerstin Hesidens and
• Jürgen Kolz

Beilstein J. Org. Chem. 2009, 5, No. 71, doi:10.3762/bjoc.5.71

• conformational analysis and MD investigations clearly confirmed the biaryl axis A to be configurationally stable at room temperature due to the second (more flexible) biaryl axis B, an (even more flexible) helical stilbene unit C and their combination with the ring-strain of the entire molecule. By experimental

Radical carbonylations using a continuous microflow system

• Takahide Fukuyama,
• Md. Taifur Rahman,
• Naoya Kamata and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2009, 5, No. 34, doi:10.3762/bjoc.5.34

• Takahide Fukuyama Md. Taifur Rahman Naoya Kamata Ilhyong Ryu Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan 10.3762/bjoc.5.34 Abstract Radical-based carbonylation reactions of alkyl halides were conducted in a microflow reactor under

The development and evaluation of a continuous flow process for the lipase- mediated oxidation of alkenes

• Charlotte Wiles,
• Marcus J. Hammond and
• Paul Watts

Beilstein J. Org. Chem. 2009, 5, No. 27, doi:10.3762/bjoc.5.27

• data was obtained using a Shimadzu QP5050A instrument with an EI ionisation source. Batch reactions were conducted using a carousel reactor/rotator (SB2, Stuart) to reduce mechanical degradation of the immobilised enzyme. Flow reactions were conducted using a displacement pump (MD-1001, Bioanalytical

Facile synthesis of two diastereomeric indolizidines corresponding to the postulated structure of alkaloid 5,9E- 259B from a Bufonid toad (Melanophryniscus)

• Angela Nelson,
• H. Martin Garraffo,
• Thomas F. Spande,
• John W. Daly and
• Paul J. Stevenson

Beilstein J. Org. Chem. 2008, 4, No. 6, doi:10.1186/1860-5397-4-6

• Institutes of Health, Bethesda, MD 20892-0820, USA 10.1186/1860-5397-4-6 Abstract A short synthesis of the postulated structure for indolizidine alkaloid 259B with the hydrogens at C5 and C9 entgegen has been achieved with complete control of stereochemistry at C5. Both diastereoisomers at C8 were obtained

Flexible synthetic routes to poison- frog alkaloids of the 5,8-disubstituted indolizidine- class I: synthesis of common lactam chiral building blocks and application to the synthesis of (-)-203A, (-)-205A, and (-)-219F

• Naoki Toyooka,
• Dejun Zhou,
• Hideo Nemoto,
• H. Martin Garraffo,
• Thomas F. Spande and
• John W. Daly

Beilstein J. Org. Chem. 2007, 3, No. 29, doi:10.1186/1860-5397-3-29

• Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, USA 10.1186/1860-5397-3-29 Abstract Background The 5,8-disubstituted indolizidines are the largest class of poison-frog alkaloids found in anuran skin, and are of considerable interest because of their inhibitory effects on the neuronal