Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• -step synthetic approach allowed the installation of a trimethylammonium (TA) head onto the 4FAB scaffold, by means of an alkyl spacer, to afford a free diffusible 4FABTA probe. TAs are known to agonize nicotinic receptors, so 4FABTA was tested on mouse brain slices and enabled reversible receptor

• . Keywords: acetylcholine receptors; bidirectional; photoswitchable drug; tetrafluoroazobenzene; visible light; Introduction Starting in 1937, azobenzenes (ABs) have attracted much attention because they undergo a photoreversible chemical transformation of the thermodynamically favored trans configuration

• regular AB-based photoswitch called "MAHoCh" [16]. The MAHoCh probe was originally designed [16] to activate nicotinic acetylcholine receptors in vivo. However, it was found that the trimethylammonium (TA) head group blocked acetylcholine binding when the photoprobe was cross-linked to the channel near

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• Wnt proteins is required for efficient binding to Frizzled receptors and the subsequent signal transduction. The carboxylesterase Notum has been shown to act as a key negative regulator of the Wnt signalling pathway by specifically mediating the depalmitoleoylation of Wnt proteins [3][4]. LP-922056 (1

Arylisoquinoline-derived organoboron dyes with a triaryl skeleton show dual fluorescence

• Vânia F. Pais,
• Tristan Neumann,
• Ignacio Vayá,
• M. Consuelo Jiménez,
• Abel Ros and
• Uwe Pischel

Beilstein J. Org. Chem. 2019, 15, 2612–2622, doi:10.3762/bjoc.15.254

• receptors for fluoride anions. Experimental General methods and materials 1H NMR spectra were recorded at 400 MHz or 500 MHz and 13C NMR spectra were recorded at 100 MHz or 125 MHz. Chloroform-d (CDCl3), acetone-d6 ((CD3)2CO) and benzene-d6 (C6D6) were used as solvents and the solvent peak was employed as

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• -protein receptors consisting of seven intermembrane domains [28]. The quaternary structure including the membrane set up the active site. Approximately 370 different G-type proteins are known, that are linked with the odour perception. Because molecules can bind to an array of olfactory receptors

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• full agonism. The compound class disclosed here can aid in new photopharmacology studies of CXCR3 signaling. Keywords: azo compounds; chemokine receptor; efficacy photoswitching; G protein-coupled receptors; photopharmacology; Introduction Photopharmacology is an emerging discipline at the interface

• activity and physiological events with light. A number of protein targets have been explored with photochromic small-molecule ligands, such as ion channels, microtubules, enzymes and GPCRs (G protein-coupled receptors) [1][10]. We focus our photopharmacology research on GPCRs [3][7][11], which constitute a

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

• Sachin S. Burade,
• Sushil V. Pawar,
• Tanmoy Saha,
• Navanath Kumbhar,
• Amol S. Kotmale,
• Manzoor Ahmad,
• Pinaki Talukdar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234

• different types of cyclic peptides as anion transporters. Gale, Luis, and co-workers [41] have separately reported the linear pseudopeptides as receptors and transporters of chloride and nitrate anions. Inspired by our recent ion transport studies with fluorinated acyclic and cyclic sugar derived peptides

Targeted photoswitchable imaging of intracellular glutathione by a photochromic glycosheet sensor

• Xianzhi Chai,
• Hai-Hao Han,
• Yi Zang,
• Jia Li,
• Xiao-Peng He,
• Junji Zhang and
• He Tian

Beilstein J. Org. Chem. 2019, 15, 2380–2389, doi:10.3762/bjoc.15.230

• ]. Compared to the conventional sensor, which is vulnerable towards the inherent background signals from the intracellular environment, the photochromic probe provides a smart strategy of well-discrimination from physiological interferences. Apart from the over-expressed ASGPr receptors on cell membranes, the

• intracellular GSH imaging in human hepatoma cell lines. The hybrid sensing system presented here provides the MnO2 nanosheets for GSH detection and Glyco-DTE reporter for dynamic fluorescence signal modulation. Besides, the high affinity of β-ᴅ-galactoside towards ASGPr receptors on the membrane of HepG2 cells

Azologization and repurposing of a hetero-stilbene-based kinase inhibitor: towards the design of photoswitchable sirtuin inhibitors

• Christoph W. Grathwol,
• Nathalie Wössner,
• Sören Swyter,
• Adam C. Smith,
• Enrico Tapavicza,
• Robert K. Hofstetter,
• Anja Bodtke,
• Manfred Jung and
• Andreas Link

Beilstein J. Org. Chem. 2019, 15, 2170–2183, doi:10.3762/bjoc.15.214

• optically control biochemical processes in the field of enzyme and ion channel modulation and recently 7TM-receptors also called GPCRs. Whereas in most approaches towards photoswitchable ligands the structure of the lead has to be changed considerable in order to incorporate a photoswitchable structural

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• receptors for molecular recognition of anionic species, pH sensors, mechanically interlocked molecules, molecular machines, and molecular reactors. Keywords: anion recognition; catenane; chalcogen bonding; click reaction; molecular reactor; hydrogen bonding; pH sensor; rotaxane; supramolecular; 1,2,3

• interactions such as hydrogen bonding, π–π stacking, electrostatic interactions, van der Waals forces, hydrophobic/solvatophobic effects and coordination bonds [2][3]. Advances in supramolecules from molecular to macroscopic size with pre-structured or functionalized receptors and multivalent binding positions

• imidazoles [8][9], polypyrroles [10][11], and indole moieties [12][13], as part of supramolecular receptors, triazole heterocycles containing macrocycles have recently been introduced as new host molecules for the selective recognition of ions, mechanically interlocked molecules (MIMs), supramolecular

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• and increase of lipophilicity are important approaches in the preparation of muramyl dipeptide analogues with improved pharmacological properties. Mannose receptors present on immunocompetent cells are pattern-recognition receptors and by mannose ligands binding they affect the immune system. Here we

• recognition receptors (PRRs) and therefore stimulate immune response and induce T cell differentiation [1][2][3]. They activate innate immune responses and contribute to the development of adaptive immunity. Immune response is initiated by the activation of PRRs located on the immune cell surface, by

• cytosolic or endosomal PRRs. PRRs are classified into: Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs) and C-type lectin receptors (CLRs) [4]. Muramyl dipeptide (MDP, N-acetylmuramyl-ʟ-alanyl-ᴅ-isoglutamine) is the smallest peptidoglycan fragment (Figure 1) capable of

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• agonist of S1P receptors while DS-SG-45 was found inactive. Dihydrosphingosines, e.g., safingol and sphinganine itself or as components of dihydroceramides are of interest as enzyme inhibitors [74][75]. Their common vicinal aminohydroxy fragment was efficiently synthesized from the aziridine ketone (2S,1

Synthesis, enantioseparation and photophysical properties of planar-chiral pillar[5]arene derivatives bearing fluorophore fragments

• Guojuan Li,
• Chunying Fan,
• Guo Cheng,
• Wanhua Wu and
• Cheng Yang

Beilstein J. Org. Chem. 2019, 15, 1601–1611, doi:10.3762/bjoc.15.164

• guest receptors [4][5]. Planar-chiral macrocyclic molecules are particularly interesting in the context of the host–guest complexation properties [6][7][8]. Pillararenes are typical examples of this type of compounds and have attracted considerable attention due to their facile chemical synthesis and

• chemical introduction of chromophores onto the rims of pillar[5]arene has been applied to allow its use as receptors for molecular sensing or biological applications [30][31][32][33]. It occurred to us that connecting fluorophores with strong absorptions in the visible range and with a high fluorescence

An azobenzene container showing a definite folding – synthesis and structural investigation

• Abdulselam Adam,
• Saber Mehrparvar and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2019, 15, 1534–1544, doi:10.3762/bjoc.15.156

• far, a series of receptors based on these macrocycles were synthesized. They have been designed for the selective recognition of sulfate ions [4][5][6], di- and triphosphate ions [7], for sensing of pyrophosphate ions in aqueous solutions [8], as receptors for phenols [9], α-chiral primary

• ][22]. Beside the usage of the side chains of the amino acids and the azole rings for molecular recognition, the functional groups of the scaffolds of these cyclopeptides have also been applied as receptors for Y-shaped anions [23] and as ligands for copper(II) complexes [24][25]. Of special interest

2,3-Dibutoxynaphthalene-based tetralactam macrocycles for recognizing precious metal chloride complexes

• Li-Li Wang,
• Yi-Kuan Tu,
• Huan Yao and
• Wei Jiang

Beilstein J. Org. Chem. 2019, 15, 1460–1467, doi:10.3762/bjoc.15.146

• –guest chemistry; macrocycles; molecular recognition; precious metal chloride complexes; Introduction Macrocyclic receptors are the major workhorses in supramolecular chemistry. Design and synthesis of new macrocyclic receptors with new properties is always attractive but is also challenging [1

• interesting new binding properties. During the last six years, our group have developed a series of naphthol-based macrocyclic receptors [24][25][26][27][28][29]. Of them, oxatub[4]arene [30][31] and zorb[4]arene [32][33] show multiple conformations due to the flipping of naphthalenes and thus resulted in a

Complexation of a guanidinium-modified calixarene with diverse dyes and investigation of the corresponding photophysical response

• Yu-Ying Wang,
• Yong Kong,
• Zhe Zheng,
• Wen-Chao Geng,
• Zi-Yi Zhao,
• Hongwei Sun and
• Dong-Sheng Guo

Beilstein J. Org. Chem. 2019, 15, 1394–1406, doi:10.3762/bjoc.15.139

• binding of the analyte gives rise to an extraordinary luminescence response of the reporter dye. Macrocyclic hosts constitute a family of well-studied artificial receptors with a discrete cavity that is selective for complementary binding to certain guests [9]. Modulation of properties of organic

• time, directed by exploring biomedical applications of these compounds. Recently, we developed a series of guanidinium-modified calixarenes as novel artificial receptors [13][14]. We achieved ultrasensitive and specific fluorescence detection of lysophosphatidic acid (a cancer biomarker) by executing

• , activatable phototheranostics could be realized via BDA when the complexed dyes are PSs, resulting in the lesion-selective imaging and targeted therapy concurrently. Besides biomedical applications, the complexation of macrocyclic receptors with dyes offers the opportunity in constructing advanced organic

Efficient resolution of racemic crown-shaped cyclotriveratrylene derivatives and isolation and characterization of the intermediate saddle isomer

• Sven Götz,
• Andreas Schneider and
• Arne Lützen

Beilstein J. Org. Chem. 2019, 15, 1339–1346, doi:10.3762/bjoc.15.133

• ][28]. Due to our interest in dissymmetric [29][30][31][32][33][34][35][36] and concave molecular building blocks [37] and their implementation in supramolecular architectures like (allosteric) receptors [38][39][40][41][42][43][44] or metallosupramolecular helicates and cages [45][46][47][48][49][50

Host–guest interactions between p-sulfonatocalix[4]arene and p-sulfonatothiacalix[4]arene and group IA, IIA and f-block metal cations: a DFT/SMD study

• Valya K. Nikolova,
• Cristina V. Kirkova,
• Silvia E. Angelova and
• Todor M. Dudev

Beilstein J. Org. Chem. 2019, 15, 1321–1330, doi:10.3762/bjoc.15.131

• between biological receptors and small ions. The complex formation behavior of water-soluble p-sulfonatocalix[4]arene and thiacalix[4]arene and group IA, IIA and f-block metal cations has been investigated computationally by means of density functional theory computations in the gas phase and in aqueous

• are not as good as those of other common macrocycles. Two positions (phenolic OH groups and p-positions) in the calixarenes’ structure can be easily modified by subsequent reactions [4]. As a result, calixarenes have a great potential as simple scaffolds to build molecular receptors and multivalent

Bambusuril analogs based on alternating glycoluril and xylylene units

• Tomáš Lízal and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2019, 15, 1268–1274, doi:10.3762/bjoc.15.124

• ; supramolecular chemistry; Introduction Macrocycles consisting of urea building blocks play an important role in supramolecular chemistry [1]. Urea N–H motifs provide macrocycles with the ability to act as anion receptors due to the stabilizing effect of N–H···anion hydrogen bonding [2][3][4]. Furthermore, the

• urea groups can participate in intermolecular hydrogen bonding resulting in the formation of tubular [5][6][7] or gel-like [8] structures. Ureas lacking of N–H hydrogen atoms such as ethyleneureas, glycolurils, and biotin are also important building blocks of macrocyclic receptors such as cucurbiturils

• with chromophore groups on their portals. However, the changes in the absorption spectra of these receptors upon anion binding were negligible since the groups on the portals were too distant from the anion binding site in the center of macrocycle. A different approach for the preparation of UV–vis

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• synthetic program towards steroid-based supramolecular receptors [28]. There, steroidal diamines and diisocyanides derived from bile acids were employed in a procedure known as MiBs, i.e., multiple multicomponent macrocyclization including bifunctional building blocks. In a series of subsequent reports

Molecular recognition using tetralactam macrocycles with parallel aromatic sidewalls

• Dong-Hao Li and
• Bradley D. Smith

Beilstein J. Org. Chem. 2019, 15, 1086–1095, doi:10.3762/bjoc.15.105

• shown that members of this tetralactam family are effective receptors for saccharides in water [65]. As shown by the X-ray crystal structure in Figure 7a, water-soluble versions of tetralactam B can nicely accommodate β-glucopyranose within the cavity [66]. There is a combination of hydrogen bonding

• elaborate lactam-based receptors with biphenyl and pyrenyl sidewalls [67][68][69], and also the tetralactam version F which has eight extra methoxy groups attached to the anthrylene sidewalls [70]. The methoxy groups provide the sidewalls with increased electron density, which leads to tighter CH···π

• cavity [71]. Conclusion The binding pockets within enzymes, lectins, and related protein receptors are amphiphilic; that is, they contain a mixture of polar and non-polar functional groups. The macrocyclic tetralactams highlighted in this review are biomimetic in that they are synthetic host molecules

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• respiratory depression and brain hypoxia [2]. Respiratory depression is a common side effect of opioid overdose and can lead to serious complications, including death. The current treatment for overdose is naloxone (NARCAN®), a competitive antagonist of µ-opioid receptors. Other treatments for opioid

• circulating in the blood stream can block the “high” by forming a drug–antibody complex incapable of passing through the blood brain barrier. Ancillary, the vaccine’s immune response can alleviate the potential for overdose by reducing the total amount of drug exposed to µ-opioid receptors that induce

Halogen bonding and host–guest chemistry between N-alkylammonium resorcinarene halides, diiodoperfluorobutane and neutral guests

• Fangfang Pan,
• Mohadeseh Dashti,
• Michael R. Reynolds,
• Kari Rissanen,
• John F. Trant and
• Ngong Kodiah Beyeh

Beilstein J. Org. Chem. 2019, 15, 947–954, doi:10.3762/bjoc.15.91

• chloride (2), and 1,4-diiodooctafluorobutane and accompanying small solvent guests (methanol, acetonitrile and water) are presented. The guests’ inclusion affects the geometry of the cavity of the receptors 1 and 2, while the divalent halogen bond donor 1,4-diiodooctafluorobutane determines the overall

• was confirmed from the increase shielding of the guest signals. These results adds to the literature of small organic guest compounds bound by N-alkylammonium resorcinarene halide receptors synergistically via HB and XB interactions. Tetravalent XB acceptor, Hex-NARBr 1, Cy-NARCl 2, divalent XB donor

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• receptor, while the other six members are G protein-coupled receptors (GPCRs). The 5-HT3 receptor is related to chemo-/radiotherapy provoked emesis and dysfunction leads to neurodevelopmental disorders and psychopathologies. Since the development of the first serotonin receptor antagonist in the early

• developmental stages my lead to altered cognitive ability, neurodevelopmental disorders, and increased incidence of psychopathologies such as autism and schizophrenia [15][16]. Serotonin operates via seven classes of 5-HT receptors of which six are G protein-coupled receptors (GPCRs) and only one, the 5-HT3R

• nicotinic acetylcholine receptors (nAChRs), γ-aminobutyric acid type A receptors (GABAARs), and glycine receptors (GlyRs). To date, five subunits of the 5-HT3 receptor are identified (5-HT3A–5-HT3E) [21]. Functional receptors are either constructed as 5-HT3A homopentamers or as heteropentamers containing 5

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• recognition by pathogen-recognition receptors during L. major-induced leishmaniasis. Keywords: adjuvant; carbohydrates; L. major; microparticle; PAMP; Introduction Recognition of parasite cell surface molecules by host immune cells initiates the first step in the immune response [1][2]. The host’s immune

• investigated how truncated oligosaccharide capping structures of LPG interact with macrophage pattern recognition receptors (PRRs) to modulate an innate immune response to L. major-induced leishmaniasis in vitro and in vivo [11][40][41][42]. These studies showed that a neutral α-1,2-trimannose capping

Design, synthesis and spectroscopic properties of crown ether-capped dibenzotetraaza[14]annulenes

• Krzysztof M. Zwoliński and
• Julita Eilmes

Beilstein J. Org. Chem. 2019, 15, 617–622, doi:10.3762/bjoc.15.57

• towards the cationic organic species [4] and ions of certain metal elements [5]. Particulary, synthetic receptors featuring crown ether moieties often equipped with extra side arms bearing pendant functional groups [6][7], have attracted a great deal of interest due to their outstanding binding ability

• whole ion pairs within the same superstructure [30], we decided to combine the two macrocyclic building blocks within the same rigidified architecture. Therefore, novel ‘crown-capped’ receptors 3a and 3b were designed to be composed of diaza-crown ether and DBTAA macrocycles. Arrangement of the two

• substituents protect the central cavity from collapsing. Simultaneously, the use of short but flexible aliphatic chains as part of the bridges make such receptors flexible enough to adjust the size of the crown cavity to the dimension of the charged entity. The new receptors 3a and 3b contain two apparently