The synthesis of well-defined poly(vinylbenzyl chloride)-grafted nanoparticles via RAFT polymerization

• John Moraes,
• Kohji Ohno,
• Guillaume Gody,
• Thomas Maschmeyer and
• Sébastien Perrier

Beilstein J. Org. Chem. 2013, 9, 1226–1234, doi:10.3762/bjoc.9.139

• conducted at 110 °C in the presence of the RAFT agent 2-(butylthiocarbonothioylthio)propionic acid (PABTC) without any additional initiator. In addition to targeting a high-molecular-weight polymer by choosing a high degree of polymerization (DP), we also prepared polymers of lower molecular weights (DP 100

• case proceeded at almost identical rates (although Figure 2B shows slight retardation at DP 100, as expected for RAFT polymerization targeting lower DPs, see above), irrespective of the DP, while similar linear semilog kinetics plots for each experiment suggest that the radical flux is constant over

• adversely affects the Mw/Mn values of the polymers at DP 4,100, which are consistently higher than those at DP 100 (compare experiments 6–10 with experiments 1–5 in Table 1). However, this is an unavoidable consequence of RAFT polymerization under these conditions, when targeting such extremely high DPs

Copper-catalyzed aerobic aliphatic C–H oxygenation with hydroperoxides

• Pei Chui Too,
• Ya Lin Tnay and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2013, 9, 1217–1225, doi:10.3762/bjoc.9.138

• present aerobic strategy for the synthesis of 1,4-diols by targeting methylene C–H oxygenation with various tertiary hydroperoxides 1 (Table 2). Generally, oxygenation of benzylic methylene C–H bonds proceeded smoothly to give the corresponding 1,4-diols 3 in good to moderate yields (77–51% yields) (Table

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• Brad M. Loertscher Yu Zhang Steven L. Castle Department of Chemistry and Biochemistry, Brigham Young University, C100 BNSN, Provo, UT, 84602, USA 10.3762/bjoc.9.132 Abstract In the context of synthetic efforts targeting the alkaloid lyconadin A, scalemic epoxide 25 was prepared by a highly

• location of the trityl ether in 26, they do provide compelling evidence that the carbon backbone of this compound is correct as drawn and is produced by a Payne rearrangement of some type. Conclusion In the context of synthetic efforts targeting the polycyclic alkaloid lyconadin A, we prepared scalemic

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• identification of small molecules targeting specific mechanisms of neuronal pathology, including glutamate excitotoxicity, mutant protein aggregation, endoplasmic reticulum (ER) stress, loss of trophic factors, oxidative stress, or neuroinflammation. Herein, we review recent advances in the discovery and

• the targeting of these mechanisms of cellular dysfunction. Currently, several drugs are in phase III clinical trials for the treatment of ALS (comprehensively reviewed in Glicksman, 2012 [3] and Dunkel et al., 2012 [5]). These drugs include dexpramipexole (2), a mitochondrial stabilizer; arimoclomol

• ]. Targeting SOD1 mutations Due to the role of SOD1 mutations in fALS and the reproduction of human ALS pathology in mouse models carrying mutant SOD1 genes, one strategy to attenuate ALS pathology is to develop small molecules that reduce SOD1 protein levels. Support for targeting SOD1 protein expression has

Synthesis of meso-substituted dihydro-1,3-oxazinoporphyrins

• Satyasheel Sharma and
• Mahendra Nath

Beilstein J. Org. Chem. 2013, 9, 496–502, doi:10.3762/bjoc.9.53

• tissue, and efficiency in generating reactive oxygen species by the absorption of photons in the visible or near IR region make them ideal candidates for developing effective photodynamic agents. These findings have encouraged researchers to design and synthesize potential targeting anticancer drugs

Synthesis of 5-(ethylsulfonyl)-2-methoxyaniline: An important pharmacological fragment of VEGFR2 and other inhibitors

• Miroslav Murár,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2013, 9, 173–179, doi:10.3762/bjoc.9.20

• . Compound 5 is used for the development of small organic compounds, i.e., modulators targeting a broad spectrum of important human protein receptors or enzymes, e.g., VEGFR2, EGFR, PDGFR, TEK kinase, ckit, EphB4, ErbB-2 receptor tyrosine kinase, cyclin-dependent kinases 2 and 4, neu receptor, polo-like

Chemical–biological characterization of a cruzain inhibitor reveals a second target and a mammalian off-target

• Jonathan W. Choy,
• Clifford Bryant,
• Claudia M. Calvet,
• Patricia S. Doyle,
• Shamila S. Gunatilleke,
• Siegfried S. F. Leung,
• Kenny K. H. Ang,
• Steven Chen,
• Jiri Gut,
• Juan A. Oses-Prieto,
• Jonathan B. Johnston,
• Michelle R. Arkin,
• Alma L. Burlingame,
• Jack Taunton,
• Matthew P. Jacobson,
• James M. McKerrow,
• Larissa M. Podust and
• Adam R. Renslo

Beilstein J. Org. Chem. 2013, 9, 15–25, doi:10.3762/bjoc.9.3

• covered here, there appears to be little rationale for targeting both cruzain and TcCYP51. On the other hand, the surprising potency of analogue 8 does suggest this as a new lead scaffold for the development of novel TcCYP51 inhibitors. We next sought to define the minimal pharmacophore within 8 required

Cyclodextrin-based nanosponges as drug carriers

• Francesco Trotta,
• Marco Zanetti and
• Roberta Cavalli

Beilstein J. Org. Chem. 2012, 8, 2091–2099, doi:10.3762/bjoc.8.235

• swelling properties. The polarity and dimension of the polymer mesh can be easily tuned by varying the type of cross-linker and degree of cross-linking. Nanosponge functionalisation for site-specific targeting can be achieved by conjugating various ligands on their surface. They are a safe and

• diagnostic applications. The surface engineering of nanosponges could lead to prolonged residence time in the blood or increased efficiency and specificity with ligands for targeting sites. In conclusion, nanosponges can be considered as multifunctional nanoscale systems suitable for the delivery of active

Preparation of mixed trialkyl alkylcarbonate derivatives of etidronic acid via an unusual route

• Petri A. Turhanen,
• Janne Weisell and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2012, 8, 2019–2024, doi:10.3762/bjoc.8.228

• metabolism, e.g., osteoporosis [2][4]. BPs are also used as bone imaging agents when linked to a gamma-emitting technetium isotope; as bone-targeting promoieties, e.g., for anti-inflammatory drugs [5]; as solvent extraction reagents for actinide ions [6]; and as a new class of herbicides [7]. Recently, BPs

Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups

• H. Bauke Albada,
• Alina-Iulia Chiriac,
• Michaela Wenzel,
• Maya Penkova,
• Julia E. Bandow,
• Hans-Georg Sahl and
• Nils Metzler-Nolte

Beilstein J. Org. Chem. 2012, 8, 1753–1764, doi:10.3762/bjoc.8.200

• and antimicrobial peptides with bacteria-specific membrane targeting modes of action (MOA) to which resistance cannot easily develop has led to high expectations in the treatment of bacterial infections [2][3][4]. Whereas host-defense peptides are found in many multicellular organisms as part of their

• activities of these RW-based synAMPs and their organometallic conjugates into perspective, two reference peptides were included, i.e., membrane-targeting gramicidin S derivative GS(K2Y2) and cell wall precursor lipid II-targeting vancomycin. For the calculations of the MIC values in µM, molecular weights of

A simple and efficient dual optical signaling chemodosimeter for toxic Hg(II)

• Sabir H. Mashraqui,
• Sapna A. Tripathi,
• Sushil S. Ghorpade and
• Smita R. Britto

Beilstein J. Org. Chem. 2012, 8, 1352–1357, doi:10.3762/bjoc.8.155

• optical targeting of toxic Hg2+ in buffered aqueous DMSO. The Hg2+-mediated desulfurization of the probe is translated into selective dual signaling of Hg2+ by means of color bleaching and fluorescence amplification while several other metal ions, including potentially competing Ag+, Cu2+ and Pb2+, afford

• conclusion, 10-methylthioacridone constitutes one of the simplest and most easily accessible chemodosimeters affording dual colorimetric and fluorescence switch-on responses for the selective and sensitive targeting of toxic Hg2+. Other merits of the chemodosimeter include visible-light excitation and

Organocatalytic asymmetric allylic amination of Morita–Baylis–Hillman carbonates of isatins

• Hang Zhang,
• Shan-Jun Zhang,
• Qing-Qing Zhou,
• Lin Dong and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2012, 8, 1241–1245, doi:10.3762/bjoc.8.139

• Hang Zhang Shan-Jun Zhang Qing-Qing Zhou Lin Dong Ying-Chun Chen Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China 10.3762/bjoc.8.139 Abstract The

An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines

• Zhiyuan Ma,
• Feng Ni,
• Grace H. C. Woo,
• Sie-Mun Lo,
• Philip M. Roveto,
• Scott E. Schaus and
• John K. Snyder

Beilstein J. Org. Chem. 2012, 8, 829–840, doi:10.3762/bjoc.8.93

• existing indole framework. In general, applications of this construction sequence fall into two major camps, namely condensations routed through a 2-aminoindole synthon [49][50][51][52][53][54][55][56], and those targeting pyridine closures onto a 2-oxindole [57][58]. In addition, intramolecular Hartwig

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• -toxin–GM1 complex is one of the most well characterized protein–carbohydrate interactions [95][96][97][98][99]. Development of inhibitors targeting the cholera-toxin protein–carbohydrate binding events is a novel strategy for disease prevention and therapy as well as for detection of the toxin in

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• but with the intention of targeting a piperidin-2-one ring-containing polycyclic scaffold, cyclic imine 5a was added at the second stage. Tetracyclic spiro-lactam 2a was isolated in high enantiomeric purity (90% ee) in good chemical yield (62%, Scheme 8) [111][112]. For the products of the nitro

Cyanoethylation of the glucans dextran and pullulan: Substitution pattern and formation of nanostructures and entrapment of magnetic nanoparticles

• Kathrin Fiege,
• Heinrich Lünsdorf,
• Sevil Atarijabarzadeh and
• Petra Mischnick

Beilstein J. Org. Chem. 2012, 8, 551–566, doi:10.3762/bjoc.8.63

• polymer particle allows for control by magnetic fields. Magnetic separation techniques or magnetic particle imaging can be performed. Applications, such as drug delivery or targeting, hyperthermia and biosensing can be realized [16][17][18]. Binding of stabilizing organic shells to ferric oxide

Synthesis and biological evaluation of nojirimycin- and pyrrolidine-based trehalase inhibitors

• Davide Bini,
• Francesca Cardona,
• Matilde Forcella,
• Camilla Parmeggiani,
• Paolo Parenti,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2012, 8, 514–521, doi:10.3762/bjoc.8.58

• further insights into the recognition requirements of the catalytic site of porcine (as the mammalian counterpart) and insect trehalase from Chironomus riparius. Both nojirimycin and pyrrolidine derivatives fall into the class of catalysis-site-targeting inhibitors [19]. On the basis of these

Mutational analysis of a phenazine biosynthetic gene cluster in Streptomyces anulatus 9663

• Orwah Saleh,
• Katrin Flinspach,
• Lucia Westrich,
• Andreas Kulik,
• Bertolt Gust,
• Hans-Peter Fiedler and
• Lutz Heide

Beilstein J. Org. Chem. 2012, 8, 501–513, doi:10.3762/bjoc.8.57

• . Escherichia coli XL1 Blue MRF, E. coli SURE (Stratagene, Heidelberg, Germany), E. coli BW 25113, and E. coli ET 12567 (pUB307) were used for cloning and were grown in liquid or on solid (1.5% agar) Luria-Bertani or SOB medium at 37 °C. The REDIRECT technology kit for PCR targeting was obtained from Plant

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

• María Martín-Rodríguez,
• Carmen Nájera,
• José M. Sansano,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2011, 7, 988–996, doi:10.3762/bjoc.7.111

• evaluation, the compounds targeting HCV replication being the most promising candidates to achieve a sustained virological response [1][4]. Several years ago, a high-throughput screening of the GlaxoSmithKline compound collection identified a series of small pyrrolidine molecules, e.g., 1 (Figure 1), able to

Advances in synthetic approach to and antifungal activity of triazoles

• Kumari Shalini,
• Nitin Kumar,
• Sushma Drabu and
• Pramod Kumar Sharma

Beilstein J. Org. Chem. 2011, 7, 668–677, doi:10.3762/bjoc.7.79

• infections even with antifungal therapy is still unacceptably high. Therefore, the development of new antifungal agents targeting specific fungal structures or functions is being actively pursued. Rapid developments in molecular mycology have led to a concentrated search for more target antifungals. Although

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• represented by three drugs targeting hypertension losartan (157, Cozaar), olmesartan (158, Benicar), eprosartan (159, Eprozar) as well as nausea (ondansetron (119, Zofran)) (Figure 5). All of these drugs aptly highlight a different synthetic approach to the imidazole core. Early antagonists of the angiotensin

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• -carboxylate (39) and 2-bromobenzaldehyde O-benzyl oxime (38), and only a moderate yield (53%) using CuI [59]. Targeting the same product, Ma et al. used copper catalysis some years previously. The coupling of 1,4-diiodobenzene (41) and (S)-ethyl 3-amino-6-hydroxyhexanoate (42), and subsequent esterification

• catalytic synthetic sequence is an inexpensive and efficient route to the target compounds (Scheme 12) [64]. A three-component coupling reaction of 2-bromobenzenethiol 57, a primary amine 58 and 1-bromo-2-iodobenzenes 59, also targeting promazine derivatives 60, was successfully under palladium catalysis

New amphiphilic glycopolymers by click functionalization of random copolymers – application to the colloidal stabilisation of polymer nanoparticles and their interaction with concanavalin A lectin

• Otman Otman,
• Paul Boullanger,
• Eric Drockenmuller and
• Thierry Hamaide

Beilstein J. Org. Chem. 2010, 6, No. 58, doi:10.3762/bjoc.6.58

• addition to the hydrophilicity conferred by the carbohydrate moiety, specific targeting may be result from coating nanoparticles with oligo- or polysaccharide chains since the carbohydrate moieties play an essential role in molecular recognition processes. Although the carbohydrate ligands occur naturally

• [1] whilst mannose units can be used for nerve cells targeting [2]. Besides naturally occurring polysaccharides, macromolecular engineering allows quite interesting possibilities for modelling of synthetic glycopolymers [3]. The hydrophobic component can be introduced by any convenient polymer moiety

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32