The activity of indenylidene derivatives in olefin metathesis catalysts

• Maria Voccia,
• Steven P. Nolan,
• Luigi Cavallo and
• Albert Poater

Beilstein J. Org. Chem. 2018, 14, 2956–2963, doi:10.3762/bjoc.14.275

• is ortho-substituted, there might be present steric repulsion with the NHCs, which might in turn facilitate the departure of the indenyl ligand [36]. Apart from reducing decomposition [37][38], this steric pressure should lead to faster rates for the initiation step of the metathesis reaction. This

• hypothesis will be examined computationally in order to assist catalyst design efforts. Results and Discussion We have studied the initiation cycle involving the transformation of the indenylidene precatalysts into the active methylidene for a series of olefin metathesis relevant complexes 1–6, using

• lengths are given in Å). Catalysts studied by DFT calculations. Precatalyst initiation in olefin metathesis (L = NHC ligand). Precatalyst initiation reaction pathway for catalysts 1–6 (M06/TZVPsdd//BP86/SVPsdd; Gibbs free energies in kcal/mol). Structural analysis for species I–III for catalysts 1–6 (in

The influence of the cationic carbenes on the initiation kinetics of ruthenium-based metathesis catalysts; a DFT study

• Magdalena Jawiczuk,
• Angelika Janaszkiewicz and
• Bartosz Trzaskowski

Beilstein J. Org. Chem. 2018, 14, 2872–2880, doi:10.3762/bjoc.14.266

• different distances from the carbene carbon. We show that the predicted initiation rates of Grubbs, indenylidene, and Hoveyda–Grubbs-like complexes incorporating these carbenes show little variance and are similar to initiation rates of standard Grubbs, indenylidene, and Hoveyda–Grubbs catalysts. In all

• investigated cases the partial charge of the carbene carbon atom is similar, resulting in comparable Ccarbene–Ru bond strengths and Ru–P/O dissociation Gibbs free energies. Keywords: catalysts; cationic carbenes; DFT; initiation; metathesis; Introduction The isolation of the first stable N-heterocyclic

• , but also on the properties and initiation rates of the most important ruthenium-based metathesis catalysts, including Grubbs, indenylidene, and Hoveyda–Grubbs complexes, as well as carbene dimerization. We also considered two different solvents: dichloromethane, which is a standard solvent for

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• ether 7a in 92% yield. Two different paths can be invoked for metathesis of compound 7a. Metathesis initiation may occur by attack of the ruthenium alkylidene at the alkyne unit to produce the more substituted vinyl alkylidine intermediate 8a which may undergo concomitant ROM–RCM with the norbornene

• nucleus to provide the triene 9a (path 1). Alternatively the metathesis initiation may occur initially at the norbornene double bond to provide the ring-opened ruthenium alkylidine intermediate 10 (path 2). The latter then undergoes RCEYM to provide the tricycle 9a. With this background a solution of the

• acetylenic unit in 17 inhibits metathesis initiation at the acetylenic unit. The norbornene derivative 17 just remains inert under metathesis conditions. Thus metathesis in these examples proceeds through path 1 (Scheme 3). Conclusion In conclusion we have developed a protocol for the synthesis of condensed

Efficient catalytic alkyne metathesis with a fluoroalkoxy-supported ditungsten(III) complex

• Henrike Ehrhorn,
• Janin Schlösser,
• Dirk Bockfeld and
• Matthias Tamm

Beilstein J. Org. Chem. 2018, 14, 2425–2434, doi:10.3762/bjoc.14.220

• initially monitored over time through gas chromatography, affording the conversion versus time diagram depicted in Figure 4. Figure 4 clearly shows that both tungsten complexes are active in the metathesis of 1-phenyl-1-propyne, with the bimetallic compound W2F3 (grey) showing a slower initiation rate

• compared to the alkylidyne complex WPhF3. For the bimetallic complex W2F3, an additional initiation step is required, in which the W≡W triple bond is cleaved and catalytically active alkylidyne species are formed. Therefore, the conversion of the substrate with catalyst W2F3 is significantly slower at the

Visible light-mediated difluoroalkylation of electron-deficient alkenes

• Vyacheslav I. Supranovich,
• Vitalij V. Levin,
• Marina I. Struchkova,
• Jinbo Hu and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2018, 14, 1637–1641, doi:10.3762/bjoc.14.139

• boron-centered radical anion 5. After the initiation event, the reaction proceeds via a chain mechanism. Thus, radical addition at the double bond gives radical 6, which abstracts a hydrogen atom from cyanoborohydride to generate boryl radical anion 5. The latter species can readily abstract the iodine

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• exploited for developing targeted cytotoxic agents: Dysregulation of translation initiation factors and regulators [14]. Mutations in epigenetic regulatory genes [15]. Overexpression of surface receptors like HER2R [16], folate receptor [17], GnRH receptor [18][19] and amino acid transporters [20

• the initiation of a clinical trial based on various PDCs consisted of two novel peptides selected after phage display that target murine A20 leukemic cells (ClinicalTrials.gov Identifier: NCT02828774). These clinical trials will focus on chronic lymphocytic leukemia (CLL). Except these two PDCs, there

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• SF5X (X = Cl, Br, SF5) across π-bonds. The unconventional conditions usually required were overcome by Dolbier’s elegant triethylborane initiation [21]. Recently, the radical arylation of a SF5-substituted alkene was realized in order to gain access to SF5-containing dihydrobenzofurans and indolines

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• positions close to the HSP1 transcription initiation site. The results suggest that when TFAM binds to the DNA, it causes significant structural changes [80]. These changes are clearly visible in the tCO–tCnitro FRET data that also indicate that the conformational changes could be consistent with DNA

• breathing. Moreover, the data demonstrated that the structural changes upon binding of TFAM near the transcription initiation site are the result of sequence-independent binding to DNA. The investigation establishes the potential of using base–base FRET for studying nucleic acid conformations in vital

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• -TNF-α, interleukin 6 (IL-6) and IL-8) thereby triggering a downstream pro-inflammatory signaling cascade aimed at the clearance of infection [8]. Thus, LPS-induced TLR4·MD-2-mediated signaling largely contributes to the development of inflammation and initiation of the beneficial defensive host

• ) [36][37], followed by a soluble accessory protein MD-2 [38] and TLR4·MD-2 complex [39] (Figure 3) [40][41][42][43][44]. TLR4 is a germ-line encoded transmembrane protein composed of an ectodomain comprising leucin-rich-repeat motifs and a cytoplasmic domain responsible for the initiation of the pro

• and lipid IVa are fully inserted into the hydrophobic binding pocket of hMD-2 which results in an efficient binding without initiation of intracellular signaling (Figure 4A) [47][62]. In contrast, upon binding of hexaacylated E. coli LPS by the MD-2∙TLR4 complex, only five long-chain acyl residues of

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• bridge. This so-called cap0 serves as quality control for correct mRNA processing and contributes to stabilization of eukaryotic mRNA [1][2], splicing [3][4], nuclear export [5], initiation of translation [6][7] and mRNA decay [8]. The most important direct interaction partners of the 5′-cap are the cap

• binding complex (CBC) [9][10] in the nucleus required for nuclear export and the eukaryotic translation initiation factor 4E (eIF4E) [11] in the cytoplasm which is indispensable for cap-dependent translation. Additionally, capped RNA serves as a marker for the innate immune system to distinguish

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• positions of the heterocycles; however, it was noticed that the regioselectivity can be tuned simply by solvent choice. Langlois and others employed catalytic metal salts for reaction initiation but Baran’s group demonstrated that metal additives were not required for a productive reaction, only trace

• metals found in Langlois’ reagent could be responsible for reaction initiation. The scope was evaluated on pyridines, pyrroles, indoles, pyrimidines, pyrazines, phthalazines, quinoxalines, deazapurine, thiadiazoles, uracils, xanthenes and pyrazolino-pyrimidines (Scheme 35). The combination of previous

Synthesis of naturally-derived macromolecules through simplified electrochemically mediated ATRP

• Paweł Chmielarz,
• Tomasz Pacześniak,
• Katarzyna Rydel-Ciszek,
• Izabela Zaborniak,
• Paulina Biedka and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2017, 13, 2466–2472, doi:10.3762/bjoc.13.243

• ',5,6-pentahydroxyflavone-based core with 2-bromoisobutyryl bromide as initiation molecule, and grafting of the PtBA arms of the flavonoid-based moiety by facile seATRP technique. To demonstrate the possibility of temporal control, on-demand seATRP was carried out utilizing multiple-step potential

• initiation sites)]/[CuIIBr2]/[TPMA] = 110/1/0.011/0.022, [tBA] = 3.4 M, [CuIIBr2/TPMA] = 0.34 mM, [TBAP] = 0.2 M, T = 65 °C. Table 1, entry 1. (a) First-order kinetic plot of seATRP with periodically applied different values of potential, between −240 mV and 600 mV vs SCE, respectively; and (b) Mn and Mw/Mn

Mechanochemical Knoevenagel condensation investigated in situ

• Sebastian Haferkamp,
• Franziska Fischer,
• Werner Kraus and
• Franziska Emmerling

Beilstein J. Org. Chem. 2017, 13, 2010–2014, doi:10.3762/bjoc.13.197

• , prolonged milling after the initiation of the reaction is not necessary for a complete conversion to the product, but accelerates the reaction. The XRPD patterns of the product for both types of experiments are comparable and the crystals obtained in the in situ reactions are of sufficient quality for X-ray

Mechanochemistry-assisted synthesis of hierarchical porous carbons applied as supercapacitors

• Desirée Leistenschneider,
• Nicolas Jäckel,
• Felix Hippauf,
• Volker Presser and
• Lars Borchardt

Beilstein J. Org. Chem. 2017, 13, 1332–1341, doi:10.3762/bjoc.13.130

• of synthesis steps and to minimize waste accumulation, at best by avoiding any solvents [7][31]. Lately, mechanochemistry has gained momentum in organic chemistry [32][33][34]. The initiation of chemical reactions by mechanical forces enables organic and inorganic syntheses without the use of any

Kinetic analysis of mechanoradical formation during the mechanolysis of dextran and glycogen

• Naoki Doi,
• Yasushi Sasai,
• Yukinori Yamauchi,
• Tetsuo Adachi,
• Masayuki Kuzuya and
• Shin-ichi Kondo

Beilstein J. Org. Chem. 2017, 13, 1174–1183, doi:10.3762/bjoc.13.116

• initiation, γ-irradiation) from hydroxy groups [11][12][13][14]. However, as the polysaccharide backbone is unstable under these harsh and high temperature conditions, these compounds are not suitable for condensation polymerizations to synthesize graft copolymers [15]. In general a radical polymerization

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

• scale of the reaction and the scheme used for its initiation, time-resolved crystallography requires either the use of fast diffraction techniques such as Laue diffraction (polychromatic beam), or the capture of intermediates by trapping methods. These trapping strategies require the complementary use

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

• initiation of translation. All these observations can be considered as archives of past metabolism [54][59], with tRNA ancestors as key support molecules. Interestingly these processes must have started with molecules shorter than the ca. 76 nucleotide-long extant tRNA, which still display a variety of forms

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• and the subsequent HWE macrocyclization are remarkable. The Trauner group in turn effectively employed various ruthenium-catalyzed reactions, including a relay ring-closing metathesis, which demonstrates the powerfulness of such a tactic even for highly elaborate substrates with several initiation

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• synthases are classed according to their intron/exon pattern [47] and their diverse reaction initiation mechanisms [48]. Genomic analyses of plant terpene synthases by Trapp and co-workers [47] revealed general organization of 12–14 introns for Class I terpene cyclases, 9 introns for Class II and 6 introns

Cyclodextrins tethered with oligolactides – green synthesis and structural assessment

• Cristian Peptu,
• Mihaela Balan-Porcarasu,
• Alena Šišková,
• Ľudovít Škultéty and
• Jaroslav Mosnáček

Beilstein J. Org. Chem. 2017, 13, 779–792, doi:10.3762/bjoc.13.77

• oligomers can be justified by water initiation of L-lactide ring opening. The relative amount of homooligolactide species is highly exaggerated in the presented ESI chromatogram (Supporting Information File 1, Figure S22) due to mass discrimination of low-molecular-weight compounds (PLA) against co-eluting

How and why kinetics, thermodynamics, and chemistry induce the logic of biological evolution

• Addy Pross and
• Robert Pascal

Beilstein J. Org. Chem. 2017, 13, 665–674, doi:10.3762/bjoc.13.66

• organisms progressed through stages of increasing DKS, then the most important transitions very likely corresponded to the initiation of cooperative associations corresponding to both an increase in complexity of the system and its dynamic kinetic stability. The ground-breaking endosymbiotic theory put

• initiation of an evolutionary process driven by an increase in DKS. The precise nature of the chemical species involved in that process remains unknown. Interestingly, however, recent investigations [74][75] have demonstrated that some kind of selective chemistry can simultaneously yield, via photochemical

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

• sequence and the hydrophobic side chain were essential for the initiation of the conjugation tube formation [11]. Soon thereafter, the consensus sequence for the isoprenylation of the cysteine in the precursor peptide was identified as the CaaX motif, in which "a" refers to an aliphatic amino acid and "X

Versatile synthesis of the signaling peptide glorin

• Robert Barnett,
• Daniel Raszkowski,
• Thomas Winckler and
• Pierre Stallforth

Beilstein J. Org. Chem. 2017, 13, 247–250, doi:10.3762/bjoc.13.27

• numerous species of social amoebae such as Polysphondylium pallidum, Dictyostelium fasciculatum [11], and D. caveatum [12], amongst others respond chemotactically to glorin (1), the acrasin has only been isolated from P. violaceum [13]. Despite its crucial role in the initiation of multicellularity, little

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

• to the initiation of two human clinical trials, a phase I/IIa trial in 2013 and a phase IIb/III trial in 2015, by the National Institutes of Health (NIH), USA. However, the administration of high doses of HP-β-CD is inevitable to obtain the effects in vivo because HP-β-CD cannot enter the cells owing

Direct arylation catalysis with chloro[8-(dimesitylboryl)quinoline-κN]copper(I)

• Sem Raj Tamang and
• James D. Hoefelmeyer

Beilstein J. Org. Chem. 2016, 12, 2757–2762, doi:10.3762/bjoc.12.272

• begin the cycle anew. The mechanism explains the metal-free direct arylation catalysis, but there has been some question about the initiation step. As KO(t-Bu) does not have sufficient reducing power to generate ArI•−, it has been proposed that initiation could arise from the reaction of ArI and KO(t-Bu