Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• , good flexibility in terms of substitution, and an unprecedented fusion pattern of the produced heterocycles. In view of the fact that the constructed 1,2,4-triazolobenzodiazepines represent a class of N-containing fused heterocycles with a new type of scaffold that is biologically interesting, the

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• calculated R-values, which were 0.83 for N50-sC18* and 0.70 for NrTP-sC18* [25]. In agreement with our recent studies sC18* exhibited an α-helical character in TFE solution (data not shown) [19]. Thus, the helical character of the novel fusion peptides likely results from the sC18* part. Furthermore, N50

• accumulated particularly around the nucleus. In addition to that, a large fraction was also centered within the nuclei and nucleoli. For the fusion peptide NrTP-sC18* a strong accumulation within the nucleoli of both cell lines was visible. Thus, former results about the preferential localization within the

• whole cell, we performed experiments using a lower peptide concentration of 1 μM. Next to this, also the shorter peptides, namely sC18*, N50 and NrTP alone were tested at these concentrations for 30 and 120 min. Hereby, no uptake at all was detected (data not shown). In contrast, both fusion peptides

Biocatalytic synthesis of the Green Note trans-2-hexenal in a continuous-flow microreactor

• Morten M. C. H. van Schie,
• Tiago Pedroso de Almeida,
• Gabriele Laudadio,
• Florian Tieves,
• Elena Fernández-Fueyo,
• Timothy Noël,
• Isabel W. C. E. Arends and
• Frank Hollmann

Beilstein J. Org. Chem. 2018, 14, 697–703, doi:10.3762/bjoc.14.58

• ABTS·+ by an excess of POD (500 U mL−1). The reactions were performed at 30 °C in oxygen-saturated 50 mM KPi buffer at pH 7.0. Flow reactor experiments PFA microreactor coils (750 μm ID) with a volume of 3 and 6 mL were constructed. The reaction mixture was introduced via a syringe pump (Fusion 200

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• (t = 0), that in creamed emulsions after 1 day reaches as high as 0.7–0.8. Such excellent stability to coalescence in high internal phase emulsions is due to the particle layer on droplet interfaces acting as a barrier to drop fusion. Between 0.20 and 0.50 wt % (middle), although an emulsion forms

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• -turns [43][44][45] and are also known to bind to a number of biological targets [46][47][48]. Interestingly, the fusion of a triazole ring to a 1,4-benzodiazepine core has resulted in an increase in the biological activity as evident from the different drugs with triazolobenzodiazepine structure such as

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• directly by fusion of thiourea/urea with 5-aminopyrazole 126 in an oil bath at 120 °C. N-Thiocarbamoyl pyrazole derivatives 180 and 183 underwent cyclization with hydrazine hydrate to give 5-(N-triazolyl)aminopyrazole derivative 182 and hydrazinopyrazolo[3,4-d]pyrimidines 185, respectively (Scheme 51). El

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

• dipeptide isostere Lys-ψ[(Z)-CF=CH]-Lys into a fusion inhibitory peptide active against HIV 1, SC29EK, was investigated [49]. Weak to moderate anti-HIV activity was observed for the fluorinated analogues, but the potency was always lower than for SC29EK. This suggested than the H-bonding behaviour was

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• (JCN). However, the fusion of the azine ring to an azolo fragment increases the number of possible alkylation sites and considerably complicates the analysis of the JCN patterns. This issue, together with the inherently low sensitivity of natural abundance 15N NMR spectroscopy, does not always permit

• -triazolo[1,5-a]pyrimidine [30], 1,2,4-triazolo[5,1-c][1,2,4]triazinone [31] and tetrazolo[1,5-b][1,2,4]triazinone [32] can be obtained by the fusion of an azine ring to an azole fragment. This method can be used for the selective incorporation of 15N atoms in different azolo-azines. Recently, we tested

• . The couplings between adamantane carbons and the nitrogens of the heterocycles are shown in Schemes 1–3. The JCN couplings observed for the C6, C7 and C8a atoms in the heterocyclic moieties of compounds 13-15N2 and 15a,b-15N2 confirmed the [1,5-b]-type fusion between the azole and azine rings in these

Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by ¹H NMR spectroscopy

• Yoshihiro Nishida,
• Mengfei Yuan,
• Kazuo Fukuda,
• Kaito Fujisawa,
• Hirofumi Dohi and
• Hirotaka Uzawa

Beilstein J. Org. Chem. 2017, 13, 1999–2009, doi:10.3762/bjoc.13.196

• glycerophospholipids are around 90%, which permits the presence of the tg conformer by ca. 10%. Note, that the tg conformer is crucial [32][33] because the antiperiplanar relation is thought to deform lamellar phases and trigger membrane fusion. With respect to the antiperiplanar tg conformer, Hauser et al. [10

A recursive microfluidic platform to explore the emergence of chemical evolution

• David Doran,
• Marc Rodriguez-Garcia,
• Rebecca Turk-MacLeod,
• Geoffrey J. T. Cooper and
• Leroy Cronin

Beilstein J. Org. Chem. 2017, 13, 1702–1709, doi:10.3762/bjoc.13.164

• , selection, fusion, and propagation. As a proof of principle, in addition to the working individual modules, we present data showing the osmotic exchange of glycylglycine containing and pure aqueous droplets, showing that the fittest droplets exhibit higher osomolarity relative to their neighbours, and

Framing major prebiotic transitions as stages of protocell development: three challenges for origins-of-life research

• Ben Shirt-Ediss,
• Sara Murillo-Sánchez and
• Kepa Ruiz-Mirazo

Beilstein J. Org. Chem. 2017, 13, 1388–1395, doi:10.3762/bjoc.13.135

• generation. Nevertheless, such division would be still stochastic, producing a significant amount of non-viable progeny, in a context in which protocell fusion and mixing would still be rife [43]. At later stages (Figure 1c) protocells getting closer to LUCA (the ‘last universal common ancestor’ species

• collaborative interactions that probably played non-trivial roles in that sense. In fact, those collective dynamics could trigger (through protocell fusion and recombination of complementary components) functional (re-)integration events beyond the minimal compartmentalized chemistries that were under primary

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• set of 48 chromosomes (their number in apes) to 46 (their number in man) in a sexed species. Starting with accidental fusion of two chromosomes, a ratchet-like continuum of changes must have distanced us from our ape ancestors. In the same way, it is implausible that there was only one origin of life

Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

• Simon Drescher,
• Vasil M. Garamus,
• Christopher J. Garvey,
• Annette Meister and
• Alfred Blume

Beilstein J. Org. Chem. 2017, 13, 995–1007, doi:10.3762/bjoc.13.99

• distributed within the disks or not. It is also conceivable that a partial demixing occurs inside the disk and that bolalipid molecules are accumulated at the rim of this disk stabilizing them against fusion into larger aggregates. With increasing amount of bolalipid, micellar structures became dominant. It

Expression, purification and structural analysis of functional GABA transporter 1 using the baculovirus expression system

• Jing Hu,
• Chris Weise,
• Christoph Böttcher,
• Hua Fan and
• Jian Yin

Beilstein J. Org. Chem. 2017, 13, 874–882, doi:10.3762/bjoc.13.88

• (GFP) fusion protein was functionally expressed in insect Sf9 cells by the BAC-TO-BAC® baculovirus expression system. A two-step procedure to purify the GAT1/GFP fusion protein from insect Sf9 cells has been established and involves immunoaffinity chromatography using self-prepared anti-GFP antibodies

• and size-exclusion fast protein liquid chromatography (SE-FPLC). A yield of 200–300 μg of the GAT1/GFP protein could be purified from 400–600 mL of infected Sf9 cells. The purified protein was analyzed by transmission electron microscopy (TEM), which revealed that the GAT1/GFP fusion protein was

• efficient observation of the expression of the protein of interest, and has a known crystal structure [28][29] for future structural studies. Results and Discussion Expression and characterization of the GAT1/GFP fusion protein in insect cells Construction and analysis of the GAT1/GFP recombinant

A novel method for heterocyclic amide–thioamide transformations

• Walid Fathalla,
• Ibrahim A. I. Ali and
• Pavel Pazdera

Beilstein J. Org. Chem. 2017, 13, 174–181, doi:10.3762/bjoc.13.20

• -one (A1) [18] was prepared by Niementowski reaction by fusion of anthranilic acid with formamide at 120 °C for 5 h. A number of quinazoline derivatives A2–A6 [19][20][21] were prepared via sequential steps starting from easily available carboxylic acid chlorides. The acid chlorides reacted with

3D printed fluidics with embedded analytic functionality for automated reaction optimisation

• Andrew J. Capel,
• Andrew Wright,
• Matthew J. Harding,
• George W. Weaver,
• Yuqi Li,
• Russell A. Harris,
• Steve Edmondson,
• Ruth D. Goodridge and
• Steven D. R. Christie

Beilstein J. Org. Chem. 2017, 13, 111–119, doi:10.3762/bjoc.13.14

• photopolymerisation [4], sheet lamination [5], powder bed fusion [6], binder jetting and direct energy deposition [7][8]. AM has gained widespread academic and industrial use for a diverse set of applications ranging from biological to aeronautical [9][10]. However, more recent research has demonstrated the benefits

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

• -Hpg7 peptide as well as the mono- and bicyclic products based on P450-catalysed turnover have been analysed in earlier studies [13][16][17]. Prior to the activity assay the substrate was loaded onto the A47934 PCP-X di-domain construct exhibiting maltose binding protein as N-terminal fusion partner

• the low levels of StaH activity [12]. In order to analyse if this effect is maintained over the subsequent amino acid cyclisation reactions in A47934 biosynthesis, we tested StaF activity using the same constructs all exhibiting MBP as N-terminal fusion partner: a PCP-X construct from A47934

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

• natural products, significant efforts have been devoted for their stereoselective syntheses [9][10][11][12][13][14][15][16]. Nevertheless, many possibilities remain unexplored especially for executing new design and synthetic strategies to generate their analogues [17][18]. On the other hand, the fusion

• [2,1-c]chromen-6a-ols 5 (Figure 1) as B-ring-modified analogues of brazilin through the fusion of chroman and tetralin motifs to generate new bioactive molecules. To the best of our knowledge, the stereoselective synthesis of such chroman-fused tetralins has never been reported. Based on the continuous

A non-canonical peptide synthetase adenylates 3-methyl-2-oxovaleric acid for auriculamide biosynthesis

• Daniel Braga,
• Dirk Hoffmeister and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 2766–2770, doi:10.3762/bjoc.12.274

• . Independently, E. coli KRX was transformed with both constructs for heterologous production of the respective N-terminally hexahistidine fusion proteins, which were purified by metal affinity chromatography (Supporting Information File 1, Figure S1). To probe their enzymatic activity, the two purified AulA

• fusion proteins were subjected to the ATP-[32P]pyrophosphate exchange assay. In this assay, the protein is incubated with a potential substrate, ATP and radioactive pyrophosphate. The reversible back exchange of [32P]pyrophosphate into ATP is quantified by scintillation counting after solid phase capture

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

• features and interesting biological activities. They have been widely isolated from fungi, lichens, bacteria, plants, and insects [1][2]. Furoisocoumarins combining a furan ring and an isocoumarin moiety are divided into two subclasses depending on their fusion type: linear furo[2,3-g]isocoumarins and

The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors

• Faith M. Akwi and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 1987–2004, doi:10.3762/bjoc.12.186

• was dipped into a temperature control bath and delivery of the reactants to the plates was enabled by two Chemyx fusion 100 classic syringe pumps. Preparation of reactant solutions Solution A (diazotized primary aromatic amine): 2,4-dimethylaniline (0.2918 g) was dissolved in approximately 0.8 mL of

• ) joined by PTFE tubing (i.d. 0.5 mm). The delivery of the reactants was enabled by three Chemyx Fusion 100 classic syringe pumps as shown in Figure 7. The reaction temperature for the diazotization (0 °C) and azo coupling (25 °C) reactions was maintained with the aid of an ice and water bath respectively

• , respectively). Using three SGE glass syringes and two 3-Way-Tee mixers (Omnifit labware, Pore size: 8.0 mm i.d., 0.5-4 mm OD), the delivery of reactant solutions A (amine + HCl solution), B (sodium nitrite solution) and C (coupler) into the PTFE tubing (i.d. 1.5 mm) was enabled by three Chemyx Fusion 100

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

• ], a crown-ether-based cyclotransferase [8], membrane fusion of small unilamellar vesicles to form giant unilamellar vesicles [9], modular methods for the affinity labeling of targeting proteins [10][11][12], and reaction acceleration on micelle interfaces [13][14]. Thus, various types of molecular

Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• uptake would result in identical rates of uptake, leading us to surmise that uptake occurred through a membrane fusion process. Driven by the desire to deliver biological payloads directly to the cytosol, we tested our system for the very challenging goal of protein delivery using green fluorescent

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

• fusion. Our calculations on octafluoronaphthalene–Ni(dpe) and –Pt(dpe) (as well as naphthalene–Pt(dpe) itself) are in good agreement with experiment. A top view of the structure is shown by 48 in Figure 14. This offers a good overlap between the LUMO in C10F8, 49, and the b2 HOMO, 5, in Pt(dpe). It was

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• formed by the head-to-tail cyclisation of two nonapeptides that are themselves derived from the C-terminal region of precursor peptides, and both heterodimers or homodimers can be formed in this process [84][144]. Along with their antimicrobial activity, these peptides can inhibit fusion of HIV-1 to host