Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

• Natascha Breuer,
• Irina Gruber,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 2684–2703, doi:10.3762/bjoc.15.262

• achieved [4]. Small molecule organic fluorophores are particularly advantageous due to the potential of a tailored fine-tuning of their photophysical properties through synthetic modifications [5]. Based on their structural features, functionalized organic chromophores, containing N-, O- or S-atoms, are

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

• VUF16216, a compound we have previously communicated as a small-molecule efficacy photoswitch for the peptidergic chemokine GPCR CXCR3. A series of photoswitchable azobenzene ligands was prepared through various synthetic strategies and multistep syntheses. Photochemical and pharmacological properties were

• of medicinal chemistry and photochemistry. Classical medicinal chemistry approaches make use of small-molecule ligands binding a target protein, thereby modifying its activity. Photopharmacological approaches use light-sensitive photochromic ligands that provide an advantageous and more precise

• 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

Experimental and computational electrochemistry of quinazolinespirohexadienone molecular switches – differential electrochromic vs photochromic behavior

• Eric W. Webb,
• Jonathan P. Moerdyk,
• Kyndra B. Sluiter,
• Benjamin J. Pollock,
• Amy L. Speelman,
• Eugene J. Lynch,
• William F. Polik and
• Jason G. Gillmore

Beilstein J. Org. Chem. 2019, 15, 2473–2485, doi:10.3762/bjoc.15.240

• small molecule organic electrochromism [6][7][9]. One example that combines photochromic and electrochromic behavior (the latter of an unusual sort) is the class of perimidinespirohexadienones 1 (PSHDs) whose synthesis, electrochemistry and UV–vis spectroscopy were reported by Minkin and co-workers [10

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• coefficient >0.8). The dye is suitable for live cell STED nanoscopy imaging and shows a nontoxic profile which makes it an appropriate candidate for medical imaging. Conclusions: We present a biocompatible, nontoxic, small molecule near-infrared dye with the option of subsequent radiolabelling and excellent

• and SiR-Mito 8 offering nontoxic, specific mitochondrial staining in live cell STED imaging. In summary, we present a biocompatible, nontoxic, small molecule near-infrared dye with the option of subsequent radiolabelling and excellent optical properties for biomedical imaging. As a compound with

• analysis of the proposed small molecule bimodal probe [18F]16 for both optical and PET imaging of cancer cells with up-regulated mitochondrial activity. Optimization of the HD rearrangement of 19 and subsequent reaction with xanthone 17 to the silicon rhodamine dye 15. Comparison of optical properties of

Isolation and biosynthesis of an unsaturated fatty acid with unusual methylation pattern from a coral-associated bacterium Microbulbifer sp.

• Amit Raj Sharma,
• Enjuro Harunari,
• Tao Zhou,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2327–2332, doi:10.3762/bjoc.15.225

• second report on the small molecule from this underexplored taxon. According to the genome sequence database, biosynthetic genes for NRPS and siderophore are present in Microbulbifer species which will be pursued in our future investigation. Experimental General experimental procedures The UV spectrum

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• small molecule size, there are few examples of its use not only in diastereoselective synthesis but also in enantioselective reactions [9][10]. Inspired by Cόrdova’s work [11][12][13], we explored the idea of merging enamine catalysis with photocatalytic oxygenation with singlet oxygen for α

Identification of optimal fluorescent probes for G-quadruplex nucleic acids through systematic exploration of mono- and distyryl dye libraries

• Xiao Xie,
• Michela Zuffo,
• Marie-Paule Teulade-Fichou and
• Anton Granzhan

Beilstein J. Org. Chem. 2019, 15, 1872–1889, doi:10.3762/bjoc.15.183

• structures appear to be biologically relevant, although a complete understanding of their roles is still missing [1][2][3]. At the same time, they represent versatile building blocks for artificial nano-architectures and nanodevices [4][5]. In this context, small-molecule fluorescent probes find applications

• ][21][22][23]. Also, there have been promising reports on cellular imaging of G4-DNA [24][25][26][27][28][29] and G4-RNA [30][31][32][33] structures using small-molecule probes. A large number of fluorescent probes for G4-DNA and RNA have thus emerged in the last years, as summarized in several recent

Mechanochemical synthesis of poly(trimethylene carbonate)s: an example of rate acceleration

• Sora Park and
• Jeung Gon Kim

Beilstein J. Org. Chem. 2019, 15, 963–970, doi:10.3762/bjoc.15.93

• on destructive approaches [7][8][9]. Recently, along with rapid progress in mechanochemical small molecule syntheses, the constructive polymeric material synthesis also succeeded. In 2014, Swager and co-workers demonstrated that poly(phenylene vinylene) could be obtained without any solvent after

Mechanochemistry of supramolecules

• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2019, 15, 881–900, doi:10.3762/bjoc.15.86

• -assembly with a high degree of compartmentalization [2]. In addition, the same building units are often used across an enormous number of structures in a reversible fashion through thermodynamic control [3]. Conversely, small-molecule synthesis is generally performed under kinetically controlled reaction

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• form the binding pocket (Figure 4) [58][59]. Utilizing a virtual screening of two different databases (i.e., the National Cancer Institute [60] and an in-house collection of 32,000 compounds), Wijfells et al. were able to identify a small-molecule mimic of the des-amino-Leu-Phe (dLF) component of the

• between FtsZ and ZipA is essential for cell division in E. coli and other Gram-negative bacteria, and therefore, it has been suggested that disruption of the ZipA/FtsZ interaction can be exploited to develop potential antibacterial molecules [83][86]. The development of a small-molecule antibiotic that

• –protein interaction, nonetheless considering the challenges involved in targeting PPIs, it is significant that the authors demonstrated by NMR that compounds from this library bind to ZipA at the FtsZ binding site and that small molecule disruptors of the ZipA/FtsZ interaction could inhibit cell division

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis

• Daniel F. Sauer,
• Johannes Schiffels,
• Takashi Hayashi,
• Ulrich Schwaneberg and
• Jun Okuda

Beilstein J. Org. Chem. 2018, 14, 2861–2871, doi:10.3762/bjoc.14.265

• and challenges and opportunities in this emerging field are shown from simple small-molecule transformations over ring-opening metathesis polymerizations to in vivo olefin metathesis. Keywords: artificial metalloprotein; β-barrel protein; metathease; olefin metathesis; ruthenium; Introduction Olefin

Copolymerization of epoxides with cyclic anhydrides catalyzed by dinuclear cobalt complexes

• Yo Hiranoi and
• Koji Nakano

Beilstein J. Org. Chem. 2018, 14, 2779–2788, doi:10.3762/bjoc.14.255

• . However, there are some burdensome requisites, such as a precise stoichiometric balance between the carboxy and hydroxy groups and an efficient removal of small molecule byproducts, for the high conversion. Another conventional method for polyester synthesis is the chain-growth ring-opening polymerization

• (ROP) of lactones and cyclic diesters [5][6][7][8][9][10]. In contrast to the step-growth polymerization, the ROP does not give any small molecule byproducts and proceeds under mild conditions. In addition, high molecular weight polyesters with narrow polydispersity can be prepared even at a low

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• Discussion PSMA has a very high affinity [39] for a small molecule homing ligand called DUPA or 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid with an inhibition constant Ki of 8 nM. Folate protein binds to folic acid and their derivatives [40] such as pteroate ligand [41] with high degree of specificity

• [42] of PSMA reveals that small molecule ligands such as DUPA would reach the PSMA active site through a gradually narrowing tunnel of amino acids of 20 Å length. Moreover, the inner surface of the PSMA tunnel possesses two hydrophobic pockets suitable for hydrophobic interactions with the amino acids

• folate receptors. The in vitro uptake study has been performed using laser scanning confocal microscopy and the bioconjugates are found to be delivered specifically to cells expressing corresponding cell surface proteins. The small molecule targeted imaging probes prepared in this study are designed for

Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor in Salmonella enterica serovar Typhimurium

• Matthew J. Styles and
• Helen E. Blackwell

Beilstein J. Org. Chem. 2018, 14, 2651–2664, doi:10.3762/bjoc.14.243

• ][48][49][50]. The majority of these compounds have been based on the AHL scaffold. The development of small molecule probes for SdiA has lagged relative to these prior studies. Indeed, to our knowledge, there have only been two reports of experimental studies of AHL-type ligand activity in SdiA in any

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• assumedly may not need to target the active site of the enzyme, but rather a different pocket or surface. To this end, further research on the exact molecular mechanism of the regulatory activity of PqsE is needed. PqsBC The small molecule 2-AA (27), which is also a secondary metabolite generated in the AQ

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• galactoside moieties are optimally oriented in space to simultaneously bind to two of the four binding sites in LecA [41]. This optimal geometric match to LecA resulted in low nanomolar inhibition of LecA. LecB has been studied in detail using multivalent and small molecule approaches. Interestingly, the

• , Titz et al. have developed small molecule LecB inhibitors derived from mannose and obtained potent monovalent inhibitors (compound 15) of LecB-mediated bacterial adhesion [47]. The sulfonamide 15 and cinnamide 16 were developed to take advantage of interactions with a nearby shallow pocket, and indeed

• plasma and liver microsomes, absence of cytotoxicity, and excellent oral bioavailability in mice. 4. Direct toxin inhibition Numerous bacteria secrete toxins that are responsible for acute virulence. Various small molecule and antibody approaches target the inhibition of bacterial toxins in order to

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• (Ac)]-GnRH-III(Dau=Aoa). Dau served as a positive control in this experiment and showed a high level of intracellular fluorescence. Considering that Dau is a small molecule and can diffuse through the plasma membrane while the conjugates can enter the cells by receptor-mediated endocytosis with low

Chiral bisoxazoline ligands designed to stabilize bimetallic complexes

• Deepankar Das,
• Rudrajit Mal,
• Nisha Mittal,
• Zhengbo Zhu,
• Thomas J. Emge and
• Daniel Seidel

Beilstein J. Org. Chem. 2018, 14, 2002–2011, doi:10.3762/bjoc.14.175

• catalyzing certain types of reactions [4][5][6]. Serving as a main source of inspiration in the design of chiral small-molecule systems, nature utilizes a variety of bimetallic and multi-metallic protein complexes to perform a host of biological functions [7]. Urease [8], hemerythrin [9], methane

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• ’-phosphitylation; phosphodiester bonds; Introduction Peptides and oligonucleotides are of exceptional importance since they are promising pharmaceutical candidates for the treatment of a range of diseases that are beyond traditional small molecule drugs [1][2][3][4][5][6][7]. Due to their iterative structures

Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae

• Bimal Koirala,
• Robert A. Hillman,
• Erin K. Tiwold,
• Michael A. Bertucci and
• Yftah Tal-Gan

Beilstein J. Org. Chem. 2018, 14, 1769–1777, doi:10.3762/bjoc.14.151

• , swarming, biofilm formation, virulence factor production and competence [3][4][5]. As such, QS has attracted significant attention as a means to control bacterial behaviors (i.e., promote productive processes while attenuating harmful traits). Extensive work aimed at developing small molecule-based QS

• gallolyticus subsp. gallolyticus [18], Streptococcus pneumoniae [19], and Lactobacillus plantarum. These circuitries are usually centered on a peptide signal, rather than a small molecule, and are fruitful ground for the development of peptide-based therapeutics. S. pneumoniae is an opportunistic human

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• -radical mediated “click” process with diverse applications in small molecule and polymer synthesis and has been reviewed [74][75][76]. The importance of the thiol-ene reaction in the synthesis of β-hydroxy sulfides is exemplified by the work of Scanlan and co-workers as shown in Scheme 41 [77][78

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• discovered and designed to competitively inhibit such interactions. Additionally, molecules that are capable of insertion between the DNA base pairs can also disfavor DNA–protein interactions directly or allosterically. Consequently, small molecule DNA binders have been in the limelight of drug-discovery

• play a significant role in target selectivity and specificity. Several focused reviews on small molecule DNA binding agents have been published in recent years. A few have updated the progresses made in disease specific DNA binders [14][15] while others have included class specific or site-specific DNA

• relevant small molecule MGBs with immense biological applications is the aryl bisamidine class related to diminazene, DAPI and pentamidine as shown in Figure 11. Minor groove complex formation between DNA duplex and pentamidine is shown in Figure 7c [83]. These small molecules are known to bind A·T-rich

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

• prodrug with enhanced plasma stability and/or cell permeability [27] and in the same time diminished toxicity for normal cells; c) covalent attachment of a drug on a tumor-targeting element (small molecule, peptide or antibody) able to selectively target and permeate cancer cells. The conjugation is being

Electrochemically modified Corey–Fuchs reaction for the synthesis of arylalkynes. The case of 2-(2,2-dibromovinyl)naphthalene

• Fabiana Pandolfi,
• Isabella Chiarotto and
• Marta Feroci

Beilstein J. Org. Chem. 2018, 14, 891–899, doi:10.3762/bjoc.14.76

• reaction under milder conditions. 2-Ethynylnaphthalene (2a) is a small molecule with a high and selective biological activity. In particular, this molecule has been demonstrated to be a selective inactivator of cytochrome P-450 2B4 [26] and an inhibitor also of other cytochrome P-450 isoforms [27]. We thus

Methyl isocyanide as a convertible functional group for the synthesis of spirocyclic oxindole γ-lactams via post-Ugi-4CR/transamidation/cyclization in a one-pot, three-step sequence

• Amarendar Reddy Maddirala and
• Peter R. Andreana

Beilstein J. Org. Chem. 2018, 14, 875–883, doi:10.3762/bjoc.14.74

• chromatography (EtOAc/hexanes) to yield pure compounds 8a–j. ORTEP diagram of compound 7a. Readily and synthetically accessible starting materials. Small molecule library of spiro[indoline-3,2'-pyrrolidine]-2,5'-dione analogs. Previously reported post-Ugi-4CR methods for the synthesis of 2-oxindoles and