Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• important feature of P&ID is that it provides a graphical representation of the control structure of the process [68][69][70]. In industry, P&ID is always made before actually implementing process automation and control for any process. More importantly, P&ID is also used for doing and evaluating HAZOP

Interactions between shape-persistent macromolecules as probed by AFM

• Johanna Blass,
• Jessica Brunke,
• Franziska Emmerich,
• Cédric Przybylski,
• Vasil M. Garamus,
• Artem Feoktystov,
• Roland Bennewitz,
• Gerhard Wenz and
• Marcel Albrecht

Beilstein J. Org. Chem. 2017, 13, 938–951, doi:10.3762/bjoc.13.95

• chains and their maximum length. Interaction of a shape-persistent CD polymer with ditopic guests. Schematic representation of tip and surface modifications realized in this study (bottom). Blue lines symbolize the CD polymers, red circles the complexed ditopic linkers. Absorption spectra of monomer 7

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

• 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

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• alkynes, i.e., capillary, packed-bed, honeycomb and monolithic reactors. A schematic representation of these reactors is shown in Figure 1. Other reactor types (e.g., fluidized bed reactor, wherein the solid catalyst is suspended in a fluid) have not been reported for liquid-phase alkyne hydrogenations

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• post-translational isoprenylation of tryptophan. (A) Schematic representation of pheromone-induced conjugation tube formation for mating in Tremella mesenterica. (B) Chemical structures of tremerogens A-10 and a-13. The isoprenyl side chains are shown in red. (C) C-terminal amino acid sequences of the

• in boldface and colored blue. (B) Chemical structures of acyl homoserine lactones. The acyl side chains are shown in boldface. (A) Schematic representation of the signal transduction cascade of quorum sensing stimulated by the ComX pheromone in B. subtilis. (B) Amino acid sequences of the aspartate

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

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• optimization, will extend and popularize the application of these methodologies. Graphical representation of (a) conventional flow cell with a saddle-shaped RF coil and (b) flow capillary with a solenoid coil. Possible geometries of NMR coils. The NMR pulse sequence used for NOESY with WET solvent suppression

Efficient access to β-vinylporphyrin derivatives via palladium cross coupling of β-bromoporphyrins with N-tosylhydrazones

• Vinicius R. Campos,
• Ana T. P. C. Gomes,
• Anna C. Cunha,
• Maria da Graça P. M. S. Neves,
• Vitor F. Ferreira and
• José A. S. Cavaleiro

Beilstein J. Org. Chem. 2017, 13, 195–202, doi:10.3762/bjoc.13.22

• ’), 112.7 (C-5’,7’), 55.2 (OCH3); UV–vis (CH2Cl2) λmax (log ε): 421 (5.90) 550 (4.19) 587 (3.46) nm. HRMS–ESI: m/z: M+• calcd for C53H36N4OZn, 808.2175; found, 808.2174. 1H NMR of β-alkenylporphyrin derivative 3a. Green arrows illustrate principal COSY correlations. Schematic representation of palladium

Dynamics and interactions of ibuprofen in cyclodextrin nanosponges by solid-state NMR spectroscopy

• Monica Ferro,
• Franca Castiglione,
• Nadia Pastori,
• Carlo Punta,
• Lucio Melone,
• Walter Panzeri,
• Barbara Rossi,
• Francesco Trotta and
• Andrea Mele

Beilstein J. Org. Chem. 2017, 13, 182–194, doi:10.3762/bjoc.13.21

• initial excitation pulse of the I spins, when the Hartmann–Hahn condition is met the magnetization is transferred from the I spins to the observed S spins. The schematic representation of the CP process is shown in the left-hand part of Figure 1. The enhanced signal of the S spins detected as a function

• fast enough so that the I spins do not behave as a whole spin system. The I*–S spin pairs are isolated from the spin network and exchange polarization in an oscillatory mode. The oscillations are damped by the spin-diffusion contact with the whole I spin system. A schematic representation of the

Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2017, 13, 10–18, doi:10.3762/bjoc.13.2

• -specific cholesterol-lowering agent. The schematic representation of the synthesis of multi-Lac-β-CD (5) is shown in Figure 1. Briefly, per-NH2-β-CD (4) was synthesized by chlorination (per-chloro-β-CD (2)) and azidation (per-azido-β-CD (3)) of primary hydroxy groups of β-CD 1, as reported previously [17

• significant. Schematic representation for synthesis of multi-Lac-β-CD (5), β-CD (1), per-chloro-β-CD (2), per-azido-β-CD (3), per-amino-β-CD, (4), multi-Lac-β-CD (DSL5.6), DSL, degree of substitution of lactose, DMAc, dimethylacetamide. MALDI–TOFMS (A) and 1H NMR spectra (B) of multi-Lac-β-CD (DSL5.6

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

• cubic arrangement of [60]fullerene dodecaacids for frameworks a) HFF-1 [57], b) HFF-2 and c) HFF-3: ORTEP representation of fullerene monomers (top, thermal ellipsoids set to 50% probability, carbon grey, oxygen red, hydrogen atoms omitted for clarity), side view indicating ABC-type packing (center) and

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• carbon atoms were found to be syn oriented. ORTEP representation of compounds 7a and 7f obtained by single crystal XRD study. Synthesis of N-alkyl vinylindoles and N-alkyl vinylindazoles (3). Retrosynthetic strategy used for the synthesis of 7 and 8. Synthesis of spiropyrrolidine compounds 7a–k and 8a

Synthesis of acylhydrazino-peptomers, a new class of peptidomimetics, by consecutive Ugi and hydrazino-Ugi reactions

• Angélica de Fátima S. Barreto,
• Veronica Alves dos Santos and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2016, 12, 2865–2872, doi:10.3762/bjoc.12.285

• ) azapeptoid, (f) hydrazinopeptide and (g) hydrazinopeptoid. Some biologically active peptoids. Biologically active hydrazinopeptides and representation of the hydrazino turn. General structure of the acylhydrazino-peptomers synthesized in this study. Retrosynthetic analysis. Synthesis of hydrazides 3a–c

Biochemical and structural characterisation of the second oxidative crosslinking step during the biosynthesis of the glycopeptide antibiotic A47934

• Veronika Ulrich,
• Clara Brieke and
• Max J. Cryle

Beilstein J. Org. Chem. 2016, 12, 2849–2864, doi:10.3762/bjoc.12.284

• cryoprotectant solution). (a) Schematic representation of the biosynthesis of A47934 by the heterotetrameric non-ribosomal peptide synthetase; the 7 modules of the A47934 NRPS machinery are distributed over 4 proteins (StaA to StaD) and exhibit the typical NRPS domain architecture with adenylation (A; purple

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• probe CA2. Library of HHQ and PQS analogues. Competitive profiling platform. A) Schematic representation of the competitive labelling strategy with an alkyne probe (green) and potential inhibitors (blue). Rh = rhodamine. B) Initial screening of our small library of HHQ (1–9) and PQS (10–16) analogues

The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot

• Philip J. Kitson,
• Stefan Glatzel and
• Leroy Cronin

Beilstein J. Org. Chem. 2016, 12, 2776–2783, doi:10.3762/bjoc.12.276

• -printing section of the robotic set-up with a 3D-printed reaction vessel showing the PP feedstock for reaction-vessel printing. Top: The three reaction vessels printed for ibuprofen synthesis on different scales; bottom left: isometric representation of a reaction vessel; bottom right: reaction vessel in

Benzothiadiazole oligoene fatty acids: fluorescent dyes with large Stokes shifts

• Lukas J. Patalag and
• Daniel B. Werz

Beilstein J. Org. Chem. 2016, 12, 2739–2747, doi:10.3762/bjoc.12.270

• case. Frontier orbital energies (DFT) and their pictorial representation for the chromophoric cores (cc) of 3, 7, and 11. Synthesis of fatty acid 3 with one olefinic unit. Synthesis of fatty acid 7 with two olefinic units. Synthesis of fatty acid 11c with three olefinic units. Spectroscopic data of

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

• [72]. Freely available CABS-FOLD uses a reduced representation approach and lets the user provide experimental distant restraints in ab initio structure prediction [66]. This method was successful when tested in CASP6 for targets for which the necessary NMR data already existed [69]. NMR data is not

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

Thiazol-4-one derivatives from the reaction of monosubstituted thioureas with maleimides: structures and factors determining the selectivity and tautomeric equilibrium in solution

• Alena S. Pankova,
• Pavel R. Golubev,
• Alexander F. Khlebnikov,
• Alexander Yu. Ivanov and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2016, 12, 2563–2569, doi:10.3762/bjoc.12.251

• can be used for the targeted synthesis of various aminothiazolidinones. OLEX2 representation of the crystal structure of thiazolidine 3b. Thermal ellipsoids are given at the 50% probability level. Fragments of the 1H NMR spectra of thiazolidine 3g at −20 °C (1), 23 °C (2) and 120 °C (3). Spectrum (1

A self-assembled cyclodextrin nanocarrier for photoreactive squaraine

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2016, 12, 2535–2542, doi:10.3762/bjoc.12.248

• , 17-C), 29.47, 29.38 (2CH2, 14-C), 28.38 (2CH, 22-C), 26.09, 26.02 (2CH2, 15-C), 25.99, 25.76 (2CH2, 16-C), 18.69 ppm; MALDI–MS (m/z): calcd for [C54H68N2O4S2]+: 872,46; found: 872,47. Schematic representation of adamantane-substituted squaraine (AdSq) binding as a divalent guest to the surface of

Construction of bis-, tris- and tetrahydrazones by addition of azoalkenes to amines and ammonia

• Artem N. Semakin,
• Aleksandr O. Kokuev,
• Yulia V. Nelyubina,
• Alexey Yu. Sukhorukov,
• Petr A. Zhmurov,
• Sema L. Ioffe and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2016, 12, 2471–2477, doi:10.3762/bjoc.12.241

• amine, 3.1 equiv of 1a, 3 equiv of K2CO3; D. 1 equiv of amine, 4.2 equiv of 1a, 4 equiv of K2CO3. Yield based on the amine used. General view of 13b in representation of atoms with thermal ellipsoids at 50% probability level; all hydrogen atoms (except for those of the NH groups) are omitted for clarity

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

• showed that benzimidazoles, Biginelli adducts, dihydropyridines, furans, pyrans, pyridinones, and thiophenes had a high representation of intrinsic greenness; whereas, a high proportion of MCRs producing chromene-4-ones, coumarins, indoles, and pyrazoles had low probabilities of achieving intrinsic

• representation of the algebraic, more abstract, problem of integer partitioning. There are two central questions that are considered in integer partitioning. The first is the determination of the total number of 2-, 3-, and 4-partitions of a ring system. In this presentation, we focus exclusively on monocyclic

• and rotating the fragment framework around the ring, either in a clockwise or anti-clockwise sense. The number and list of permutations of these dissection maps defines the chemical space of possibilities for building up a specified ring framework and is the precise visual representation of the

Solvent-free, visible-light photocatalytic alcohol oxidations applying an organic photocatalyst

• Martin Obst and
• Burkhard König

Beilstein J. Org. Chem. 2016, 12, 2358–2363, doi:10.3762/bjoc.12.229

• a stirrer, and an LED frame with 5 LEDs (λ = 455 nm). Figure 1 shows a schematic representation and photographs. Before reaction, the solid substrate and photocatalyst are gently homogenized with a spatula, followed by grinding with pestle and mortar. The reaction mixture is then filled into the

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• ), isatins 3 (0.5 mmol), and sarcosine (0.5 mmol) in the mixture of acetonitrile (30 mL) and chloroform (10 mL) for 72 h. Key interactions in {1H-13C}HMBC spectrum of 4f. General view of 4c in the crystal in thermal ellipsoids representation (50% probability). Hydrogen atoms connected to carbon atoms are

• omitted for clarity. General view of 4e in the crystal in thermal ellipsoids representation (40% probability). Hydrogen atoms connected to carbon atoms are omitted for clarity. General view of 4r in the crystal in thermal ellipsoids representation (50% probability). Hydrogen atoms connected to carbon