(CF₃CO)₂O/CF₃SO₃H-mediated synthesis of 1,3-diketones from carboxylic acids and aromatic ketones

• JungKeun Kim,
• Elvira Shokova,
• Victor Tafeenko and
• Vladimir Kovalev

Beilstein J. Org. Chem. 2014, 10, 2270–2278, doi:10.3762/bjoc.10.236

• JungKeun Kim Elvira Shokova Victor Tafeenko Vladimir Kovalev Laboratory of Macrocyclic Receptors, Department of Chemistry, Moscow State University, Lenin’s Hills, Moscow 119991, Russia 10.3762/bjoc.10.236 Abstract A very simple and convenient reaction for 1,3-diketone preparation from carboxylic

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• confirming the proposed stereochemistry [49]. Glutamate metabotropic receptor agonists (2000, 2007) The metabotropic glutamate receptors (mGluRs) are members of the vast family of G-protein coupled receptors which are expressed throughout the central nervous system. They consist of at least eight sub-types

Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

• Vincent Fagan,
• Istvan Toth and
• Pavla Simerska

Beilstein J. Org. Chem. 2014, 10, 1741–1748, doi:10.3762/bjoc.10.181

• specific pattern recognition receptors (PRRs) found on immune cells. PRRs recognize conserved pathogen-associated molecular patterns. This leads to activation of cells of the innate and adaptive immune system, resulting in significantly enhanced immune responses [6]. By preparing agonists for a particular

Bifunctional dendrons for multiple carbohydrate presentation via carbonyl chemistry

• Davide Bini,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2014, 10, 1686–1691, doi:10.3762/bjoc.10.177

• ; Introduction Recognition processes between glycans and their receptors are of paramount relevance in several biological phenomena, both in physiological [1][2] and in pathological [3][4][5] conditions. These processes can be exploited in diagnostic tools [6][7], in nanobiotechnology applications [8], and in

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• kinase receptors and play an important role in related drug discovery [15]. To facilitate the discovery of lead compounds as anticancer reagents from marine nucleosides [16][17][18], the total synthesis of trachycladines A and trachycladines B are reported herein allowing to assemble their unique

Photoswitchable precision glycooligomers and their lectin binding

• Daniela Ponader,
• Sinaida Igde,
• Marko Wehle,
• Katharina Märker,
• Mark Santer,
• David Bléger and
• Laura Hartmann

Beilstein J. Org. Chem. 2014, 10, 1603–1612, doi:10.3762/bjoc.10.166

• azobenzene unit allows for the photosensitive control of glycoligand binding to protein receptors. These stimuli-sensitive glycoligands promote the understanding of multivalent binding and will be further developed as novel biosensors. Keywords: azobenzene; glycopolymer; lectin binding; multivalency

Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

• Candace K. Goodman,
• Mark L. Wolfenden,
• Pratima Nangia-Makker,
• Anna K. Michel,
• Avraham Raz and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2014, 10, 1570–1577, doi:10.3762/bjoc.10.162

• , apoptosis, angiogenesis, and B cell activation [8][9][10]. Galectin-3 has been reported to be involved in mechanisms that cluster cell surface glycoproteins [10][11], cross-link receptors [12], and form lattices and larger aggregates [13]. Structurally, galectin-3 is composed of one carbohydrate recognition

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

• Scientifico e Tecnológico, 50019 Sesto Fiorentino, Firenze, Italy 10.3762/bjoc.10.156 Abstract Intermolecular interactions involving carbohydrates and their natural receptors play important roles in several biological processes. The development of synthetic receptors is very useful to study these recognition

• : 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

• already successfully applied to peptides and proteins in recent years [15][21][27][28][29][30][31][32][33][34][35][36]. The interaction of sugar molecules with receptors has been studied and shown that the recognition process involves many hydrogen bonds between the two molecules [1][37]. Aqvist et al

Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• years the study of pattern recognition receptors (PRRs) and associated ligands has evolved tremendously [1]. The discovery of Toll-like receptors (TLRs) [2] in the late 1990s has had a major impact on the field of immunology. This is reflected in the exploration of conjugates consisting of a PRR-ligand

• -binding oligomerization domain (NOD) receptors [17] NOD1 [18] and NOD2 [19] were discovered to be intracellular PRRs [20][21]. NOD1 and NOD2 recognize specific parts of peptidoglycan (PG), found in the bacterial cell wall [22][23]. PG consists of a polysaccharide chain of β-(1–4) linked N

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• higher affinity for receptors as described for Shiga-like toxins [16] and other systems [17]. Several excellent reviews have been published on PEGylation of proteins, including PEG-drugs in the market [2][18][19][20][21]. However, PEGylation of carbohydrate molecules has been less exploited and studies

• been PEGylated and introduced in the surface of polystyrene nanoparticles in order to increase the interaction with galactose receptors. p-Aminophenyl β-D-galactopyranoside was coupled with a bifunctional PEG activated on one end with NHS for the combination with the aniline and a FMOC-protected amino

• ]. Mannose was also PEGylated in order to target drugs specifically to mannose receptors present in liver endothelial cells. Mannosyl PEGylated polyethylenimine (PEI) conjugates were synthesized either by direct coupling the mannose and the PEG chain to the PEI backbone (Figure 3A) or by attaching the

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives

• Giordano Lesma,
• Fiorella Meneghetti,
• Alessandro Sacchetti,
• Mattia Stucchi and
• Alessandra Silvani

Beilstein J. Org. Chem. 2014, 10, 1383–1389, doi:10.3762/bjoc.10.141

• receptors [5]. In particular, 3,3-disubstituted 3-amino-2-oxindoles are present in several drug candidates. They exhibit various types of bioactivity, such as the potent gastrin/CCK-B receptor antagonist I [6], the vasopressin VIb receptor antagonist II [7][8], the CRTH2 (DP2) receptor antagonist

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• wide range of physiological processes and the development of synthetic carbohydrate receptors (“synthetic lectins”) constitutes a key advance in biomedical technology. In this article we report a synthetic lectin that selectively binds to carbohydrates immobilized in a molecular monolayer. Inspired by

• spots, high-edge resolution, good reproducibility and short reaction times can be easily achieved by using µCP. These advantages render this method a versatile tool for the fabrication of simple carbohydrate microarrays. “Synthetic lectins” as artificial carbohydrate receptors would be highly valuable

• biomimetic carbohydrate receptors [39]. To this end, we explored a dynamic combinatorial library of cyclic peptides to select receptors that are assembled from tripeptides under thermodynamic equilibrium. Amongst others, we identified a synthetic lectin (HisHis) that binds N-acetylneuraminic acid (NANA) [18

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• 1 mg of GNPs was calculated to be ~0.1 μmol (the detailed calculation is given in Supporting Information File 1). Cellular experiments with lamivudine (3TC) and abacavir (ABC)-GNPs TZM-bl cells (derived HeLa-cell immortalized cell line that expresses high levels of CD4 and co-receptors CXCR4 and

• assay: The ability of lamivudine and abacavir-GNPs to block HIV-1 infection was tested using a luciferase reporter cell line (TZM-bl) as described in [36]. TZM-bl is a Hela cell line that stably expresses CD4, CCR5 and CXCR4 (viral receptor and co-receptors). These cells also contain separate integrated

Human dendritic cell activation induced by a permannosylated dendron containing an antigenic GM₃-lactone mimetic

• Renato Ribeiro-Viana,
• Elena Bonechi,
• Javier Rojo,
• Clara Ballerini,
• Giuseppina Comito,
• Barbara Richichi and
• Cristina Nativi

Beilstein J. Org. Chem. 2014, 10, 1317–1324, doi:10.3762/bjoc.10.133

• they are able to control self-tolerance as well as induce an effective immune response [13][14]. They provide an essential link between innate and adaptive immune responses [13]. They survey the environment and, based on the typical non-clonal recognition receptors of the innate immune system, they

• strategies is to arm DCs with tumor-specific antigens. This issue has successfully been achieved by either culturing ex vivo DCs [16][17] from bone marrow precursors or more recently by targeting in vivo DC receptors with specific mAbs conjugated to tumor antigens [18][19]. In both cases, the development of

• persistence, the timing and the pathways essential for enhancing DC maturation and for licensing the antigen-loaded DCs in the T cell zone of lymph nodes [10]. Concerning the DCs maturation step, triggering C-type lectin receptors (CLRs) is crucial to enhance the antitumor immunity [10][20]. In particular

Homochiral BINOL-based macrocycles with π-electron-rich, electron-withdrawing or extended spacing units as receptors for C₆₀

• Marco Caricato,
• Silvia Díez González,
• Idoia Arandia Ariño and
• Dario Pasini

Beilstein J. Org. Chem. 2014, 10, 1308–1316, doi:10.3762/bjoc.10.132

• macrocycles [16], and urea-based structures [17] have all been exploited to develop the nanotube concept. Efficient supramolecular receptors for C60 and higher fullerenes have been already reported in the literature and research in this area is still very active [18][19]. Jasti and co-workers have

Synthesis of a sucrose dimer with enone tether; a study on its functionalization

• Zbigniew Pakulski,
• Norbert Gajda,
• Magdalena Jawiczuk,
• Jadwiga Frelek,
• Piotr Cmoch and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2014, 10, 1246–1254, doi:10.3762/bjoc.10.124

• designed for such receptors, sugars are the most promising due to their availability and biocompatibility. Up to date only monosaccharides have found a wide application in the synthesis of crown ether analogs [5][6]. The disaccharide scaffold is much less pronounced [7]. During the past decade we have

• ; Figure 1). Such receptors exhibit interesting complexing properties towards chiral ammonium salts including amino acids [10][11][12][13][14]. More complex sucrose macrocycles, such as 5, are available, although in rather low yield [15]. In this paper we present an approach to other derivatives containing

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• as food intake, energy homeostasis, cancer, cell proliferation, blood pressure and epilepsy [122][123]. Those effects are mediated by four distinct G protein-coupled receptors (Y1, Y2, Y4, Y5) that are expressed in central and/or peripheral tissues. SPPS offers a great opportunity to synthetically

• substitutions by alanine [124] or hydrophobic/ionic monomers [125] can help to identify key binding sites of peptides and their individual receptors. In addition, it is possible to perform cyclization [126] or modification of NPY with unnatural amino acids [127]. Cabrele et al. reported on a tyrosine methyl

Synthesis of zearalenone-16-β,D-glucoside and zearalenone-16-sulfate: A tale of protecting resorcylic acid lactones for regiocontrolled conjugation

• Hannes Mikula,
• Julia Weber,
• Dennis Svatunek,
• Philipp Skrinjar,
• Gerhard Adam,
• Rudolf Krska,
• Christian Hametner and
• Johannes Fröhlich

Beilstein J. Org. Chem. 2014, 10, 1129–1134, doi:10.3762/bjoc.10.112

• cause problems of the reproductive tract (e.g., impaired fertility) in animals [7]. Physiological studies revealed binding of ZEN to recombinant human estrogen receptors [8] and have furthermore shown a ZEN-induced stimulation of the growth of human breast cancer cells [9]. Additionally, masked

Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• the identification of new potent and selective ligands of ionotropic and metabotropic glutamate receptors (GluRs). To this aim, bicycle compound Ib was designed and synthesised from D-serine as novel [2.3]-spiro analogue of L-Glu. This frozen amino acid derivative was designed to further limit the

• ; Introduction L-Glutamic acid (L-Glu) is the primary excitatory neurotransmitter in the mammalian central nervous system (CNS) playing a critical role in the learning and memory process [1][2][3]. L-Glu receptors can be subdivided in ionotropic receptors (NMDA, AMPA and kainite receptors) [4][5] and G-protein

• coupled or metabotropic glutamate receptors (mGluRs) [6][7]. To date, eight different metabotropic receptor subtypes (mGluR1–8) have been identified. Compounds that modulate the function of the mGluRs might be useful for treating a wide range of CNS disorders including schizophrenia, depression, anxiety

Molecular recognition of isomeric protonated amino acid esters monitored by ESI-mass spectrometry

• Andrea Liesenfeld and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 825–831, doi:10.3762/bjoc.10.78

• acid derivatives. The performance of the receptors was evaluated by ESI-mass spectrometry using the isomer labelled guest method (ILGM). This method revealed the preferred binding of L-norleucine and L-leucine compared to L-isoleucine for both receptors. Furthermore, non-covalent isotope effects

• to use this motif to achieve binding of the leucine isomers as their protonated ester derivatives. This provides the major part of the overall binding energy. However, to distinguish the three isomers the receptors need to provide further elements that either provide additional binding sites for the

• scaffold that has been demonstrated to be a valuable part of some receptors [12][13], we decided to employ this motif. Therefore, we designed the two compounds 1 and 2 shown in Figure 2 that differ only in the bridging element between the crown ether group and the spirobifluorene. The synthesis of 1 and 2

Towards allosteric receptors – synthesis of β-cyclodextrin-functionalised 2,2’-bipyridines and their metal complexes

• Christopher Kremer,
• Gregor Schnakenburg and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 814–824, doi:10.3762/bjoc.10.77

• bringing together or separating the cyclodextrin moieties from each other. Keywords: allosteric receptors; 2,2’-bipyridines; β-cyclodextrin; supramolecular chemistry; metal complexes; Introduction In biological systems, recognition events play a major role to guarantee the selectivity of essential

• ]. Depending on the substitution pattern for the central 2,2’-bipyridines, three conceptually different types of allosteric receptors can be obtained: 4,4’- or 6,6’-substitution, both leading to positive allosteric receptors, meaning that they adopt an open anti-conformation in the free state where the two

• for our allosteric receptors [20][21][22]. Hence, we also started with these here. Unfortunately, silver(I) ions turned out to be not effective in this case. Although, they seem to form complexes with compounds 1–3, we did not observe any of the characteristic shifts of the signals assigned to the

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Studies toward bivalent κ opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity

• Thomas A. Munro,
• Wei Xu,
• Douglas M. Ho,
• Lee-Yuan Liu-Chen and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2013, 9, 2916–2924, doi:10.3762/bjoc.9.328

• affinity for opioid receptors [1]. In particular, most modifications of the furan ring tested to date dramatically reduce affinity for κ-OR [1], although small substituents at C-16 have little effect (Figure 1). Unexpectedly, epimerization at C-12, inverting the configuration of the furan ring, reduces

• ), naltrindole [10], β-funaltrexamine [11], and the NOP antagonist C-24 [16]. Beyond opioids, ionic H-bonds to Asp3.32 are conserved across biogenic amine receptors; indeed, this residue3.32 interacts with the ligand in almost all GPCR crystal structures reported to date [17]. In summary, 1 appears to bind

Novel supramolecular affinity materials based on (−)-isosteviol as molecular templates

• Christina Lohoelter,
• Malte Brutschy,
• Daniel Lubczyk and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2013, 9, 2821–2833, doi:10.3762/bjoc.9.317

• significant application as receptors and chemical sensors in the detection of aromatic compounds [16][17][18][19][20]. Thus, the first artificial receptor for caffeine had been established [21][22]. The introduction of chiral information onto a supramolecular entity gave rise for enantiofacial differentiation

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• the FPR2 and GPR32 types of G-Protein-coupled receptors, the receptor(s) for RvD2 remain to be identified. Identification of the receptors mediating the combined anti-inflammatory and antimicrobial actions would facilitate efforts to identify ligands that have better drug-like properties than RvD2 or