Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• the complex interactions between cells and pathogens, e.g., the human immunodeficiency virus (HIV-1) [6]. The HIV-1 envelope protein is present as a C3-symmetric trimer on the viruses’ surface [7], and the virus entry into the cell is mediated by its interactions with cellular receptors. To explore

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• as the neurotransmitter is best recognized. For detailed studies of interactions with receptors a number of structural analogues of glutamic acid are required to map their active sides. This review article summarizes syntheses of nonracemic hydroxyglutamic acid analogues equipped with functional

• ]. Several derivatives of L-glutamic acid functioning as anticancer agents have been reported [4]. But primarily L-glutamic acid is known as the major excitatory neurotransmitter in central nervous system which acts by binding to glutamate receptors [5][6][7]. However, these interactions are linked to

• several neurodegenerative diseases (Alzheimer [8], Huntington [9], Parkinson [10]) as well as to stroke [11] and epilepsy [12]. Two main classes of receptors, each of them containing three subclasses which are further divided into subtypes have been established for glutamic acid. To understand the

First synthesis of cryptands with sucrose scaffold

• Patrycja Sokołowska,
• Michał Kowalski and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2019, 15, 210–217, doi:10.3762/bjoc.15.20

• ’,4,4’-penta-O-benzylsucrose and 1’,2,3,3’,4,4’-hexa-O-benzylsucrose. Keywords: cryptands; macrocyclization; sucrose; Introduction The design and synthesis of macrocyclic receptors is one of the main challenges of supramolecular chemistry [1][2]. These artificial systems exhibit interesting properties

• ]. There are also reports on the preparation of ‘distorted’ cyclodextrins in which diverse fragments are incorporated into the original oligosaccharide ring(s) [5]. Another class of sugar receptors is represented by macrocyclic derivatives with the carbohydrate unit being a part of a crown or aza-crown

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• targeting of the conjugate towards a specific molecular structure that has been identified to be characteristic for a diseased state of cells and tissues. Particularly G protein-coupled receptors (GPCRs) that are endogenously activated by agonistic peptide or protein ligands can be suitable target

• structures. Many peptide or protein ligand receptors have been associated with various diseases, e.g., cancer malignancies [17]. Amongst the GPCRs, the neuropeptide Y (NPY) receptor family comprises four closely related receptor subtypes in human (hY1R, hY2R, hY4R, and hY5R) that have been discussed in the

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• pili on the cell surface (discussed further below). C-Type lectin C-Type lectins are one of the largest and most diverse lectin families, including the Mtb-recognizing eukaryotic host immune receptors DC-SIGN, Dectin-1/2, Mincle, MCL, and MR, mentioned before. These lectins bind carbohydrates in a

N-Acylated amino acid methyl esters from marine Roseobacter group bacteria

• Hilke Bruns,
• Lisa Ziesche,
• Nargis Khakin Taniwal,
• Laura Wolter,
• Thorsten Brinkhoff,
• Jennifer Herrmann,
• Rolf Müller and
• Stefan Schulz

Beilstein J. Org. Chem. 2018, 14, 2964–2973, doi:10.3762/bjoc.14.276

• receptors in roseobacters [21]. Instead, they show moderate antialgal activity [21]. In contrast to AHLs, the acyl chain can also be terminally oxidized [24]. During our analyses of different Roseobacter isolates, we encountered several compounds, which mass spectra show similarities to known NAMEs. These

• on the LuxR type receptors for AHLs in bacteria [23][24]. Other potential functions are antimicrobial or cytotoxic activity of the tested derivatives. Roseovarius sp. D12_1.68 showed antimicrobial activity against a Rhodobacteraceae sp. TL and antialgal activity against Skeletonema costatum while

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

• the HTS approaches used to identify small molecules which will typically target enzymes (e.g., kinases and proteases) or extracellular receptors [79]. Recently, a HTS strategy to identify inhibitors of the Klebsiella pneumonia SSB PPI was reported. Starting from a library of more than 72,000 compounds

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• ]. Poirier et al. proved that 13α-derivatives of 3,17-estradiols have reduced binding affinity for estrogen receptor alpha and display no uterotropic activity [19]. The conformational change resulting from the inversion at C-13 leads to an epimer unable to bind to its nuclear receptors. We have recently

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

• the cell surface of prostate, brain, bladder and breast cancers. Whereas folate receptors are attached to the cell membrane by a glycophosphatidylinositol anchor and over-expressed on several cancers as well as activated macrophages during inflammation. Moreover, folate receptors were also discovered

• which express neither PSMA nor folate receptors [panels (iv) and (viii)]. The absence of any rhodamine B bioconjugates 13 and 17 uptake in the cytoplasm of negative cell line, PC-3 cells, show that the bioconjugates are very specific which is an important criterion in targeted drug delivery systems for

• avoiding off-site toxicity. In vitro specificity of bioconjugates, 13 and 17 were further examined by prior incubation of LNCaP cells and CHO-β cells with 100-fold excess of 2-PMPA and folic acid to block PSMA and folate receptors, respectively. Receptor blocked LNCaP and CHO-β cells display minimal uptake

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

• , host colonization, and biofilm formation at high population densities. This cell–cell signaling process is regulated by N-acyl L-homoserine lactone (AHL) signals, or autoinducers, and LuxR-type receptors in Gram-negative bacteria. SdiA is an orphan LuxR-type receptor found in Escherichia, Salmonella

• , Klebsiella, and Enterobacter genera that responds to AHL signals produced by other species and regulates genes involved in several aspects of host colonization. The inhibition of QS using non-native small molecules that target LuxR-type receptors offers a non-biocidal approach for studying, and potentially

• intracellular LuxR-type receptors (Figure 1A) [13]. The AHL signals are produced at a low, but constant basal level, and rapidly diffuse into the local environment. As the population grows, so does the concentration of AHL, and once it reaches a threshold intracellular level (and thus a “quorum” has been

Transition metal-free oxidative and deoxygenative C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyl lithium as an efficient synthetic approach to azaheterocyclic carboranes

• Lidia A. Smyshliaeva,
• Mikhail V. Varaksin,
• Pavel A. Slepukhin,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2018, 14, 2618–2626, doi:10.3762/bjoc.14.240

• capture therapy (BNCT) of cancer [8][9][10][11][12], as well as agonists and antagonists of biological receptors [13][14][15][16][17], etc. In addition, azaheterocyclic carboranes are actively used as ligands in the synthesis of metal complexes of various architectures, possessing catalytic activity [18

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

• , Hungary 10.3762/bjoc.14.226 Abstract Background: Peptide hormone-based targeted tumor therapy is an approved strategy to selectively block the tumor growth and spreading. The gonadotropin-releasing hormone receptors (GnRH-R) overexpressed on different tumors (e.g., melanoma) could be utilized for drug

• approaches to diminish this kind of cytotoxic effects on healthy tissues is the employment of drug delivery systems directed specifically to cancer cells. The chemotherapeutic drug targeting is often based on the receptors for certain peptide hormones that are preferentially expressed by cancer cells. The

• utilization of these receptors for cancer cell targeting allows for minimizing the toxic side effects and producing high drug concentration selectively at the tumor site. In general, drug delivery systems consist of a targeting moiety in order to recognize a receptor on tumor cells and a cytotoxic drug

Calixazulenes: azulene-based calixarene analogues – an overview and recent supramolecular complexation studies

• Paris E. Georghiou,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Hidetaka Nishimura,
• Jaehyun Lee,
• Atsushi Wakamiya and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2018, 14, 2488–2494, doi:10.3762/bjoc.14.225

• investigated. Keywords: azulene; calixarenes; calixazulenes; supramolecular chemistry; tetraalkylammonium salts; Introduction Among the great variety of synthetic macrocyclic molecular receptors which have been reported, those that are referred to by their generic name “calixarene” loom large [1][2][3]. The

Semi-synthesis and insecticidal activity of spinetoram J and its D-forosamine replacement analogues

• Kai Zhang,
• Jiarong Li,
• Honglin Liu,
• Haiyou Wang and
• Lamusi A

Beilstein J. Org. Chem. 2018, 14, 2321–2330, doi:10.3762/bjoc.14.207

• spinosyn molecule interacts with both gamma-aminobutyric acid (GABA) receptor and nicotine acetylcholine (NACh) receptors [9]. Spinosad and spinetoram can be degraded via a combination of photolysis and microbial action, ultimately producing CO2, H2O, and nitrogen oxides [10]. That suggests that along with

Synthesis and post-functionalization of alternate-linked-meta-para-[2ⁿ.1ⁿ]thiacyclophanes

• Wout De Leger,
• Koen Adriaensen,
• Koen Robeyns,
• Luc Van Meervelt,
• Joice Thomas,
• Björn Meijers,
• Mario Smet and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2190–2197, doi:10.3762/bjoc.14.192

• homodithiacalix[4]arenes by dynamic covalent chemistry [12][13][14]. Functionalization of homothiacalix[4]arenes was made possible by changing the precursors before macrocyclization (Scheme 1) [12]. Recently, pillar[n]arenes have attracted much interest as new supramolecular receptors due to their pillar-shaped

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• /bjoc.14.173 Abstract The synthesis of new calix[4]arenes adopting a cone stereoisomeric form bearing two or four azide fragments on the upper rim and water-soluble triazolyl amphiphilic receptors with two or four polyammonium headgroups via copper-catalyzed azide–alkyne cycloaddition reaction has been

• are very important as a universal energy source and as intracellular mediators in many biological processes [6]. In the cellular metabolism, adenosine 5'-triphosphate (ATP) is hydrolyzed to adenosine 5'-monophosphate (AMP) or adenosine 5'-diphosphate (ADP) by enzymes [7]. Thus, the receptors for

• nucleotides must possess selectivity towards these anions. From this point of view, nucleotide receptors based on polyammonium cations are of great demand because the electrostatic interactions of such polyammonium systems and negatively charged phosphates are strong. Hydrogen bonding [8] and π-stacking

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• and yields of the Michael reactions. Supramolecular catalysis has drawn tremendous interest in the past few years [15][16][17][18][19][20][21][22][23]. In this context, calixarenes are ideal supramolecular macrocyclic scaffolds for the design of molecular receptors and organocatalysts due to their

Strong binding and fluorescence sensing of bisphosphonates by guanidinium-modified calix[5]arene

• Jie Gao,
• Zhe Zheng,
• Lin Shi,
• Si-Qi Wu,
• Hongwei Sun and
• Dong-Sheng Guo

Beilstein J. Org. Chem. 2018, 14, 1840–1845, doi:10.3762/bjoc.14.157

• particularly suitable for the detection of analytes lacking chromophores. The key factor in IDA is the rational design of artificial receptors that are capable of binding analytes strongly and specifically. Calixarenes are the third generation of macrocyclic receptors after crown ethers and cyclodextrins. Due

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

• the CSP signal that they produce (CSP1 and CSP2, Figure 1) and their cognate receptors (ComD1 and ComD2, respectively), with minimal cross-talk between the groups [28]. The two CSP signals share approximately 50% homology and differ mainly in hydrophobic residues in the central region of the peptides

• for ComD1 binding [19]. Moreover, three of these positions, 4, 7 and 8, were suggested by Johnsborg et al. to confer specificity between the ComD receptors [29]. Therefore, in this work, we aimed to define the hydrophobic pockets within the ComD1 receptor that are occupied by the hydrophobic residues

• peptide to assess the occupancy level and degree of specificity. Since no structural information is available for the ComD receptors, we chose to assess the ComD1 binding pocket by synthesizing a set of CSP1 analogs bearing highly conservative point mutation in key hydrophobic positions (4, 7, 8, 11, 12

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• functionalized [54][55][56]. It is noteworthy that the calix[4]arene skeleton has been already exploited for the development of multivalent glyco- and peptidocalixarenes that can be recognized by cell-membrane receptors [57][58][59] and of calixarene derivatives able to specifically target membrane proteins

• that calixarenes themselves display antibacterial, antiviral, and anticancer properties [64]. Herein, we describe the synthesis of a multivalent phototherapeutic agent designed in order to specifically target membrane receptors involved in the angiogenesis process. The multivalent system is composed of

Host–guest complexes of conformationally flexible C-hexyl-2-bromoresorcinarene and aromatic N-oxides: solid-state, solution and computational studies

• Rakesh Puttreddy,
• Ngong Kodiah Beyeh,
• S. Maryamdokht Taimoory,
• Daniel Meister,
• John F. Trant and
• Kari Rissanen

Beilstein J. Org. Chem. 2018, 14, 1723–1733, doi:10.3762/bjoc.14.146

• , aiding in the binding of polar guests such as N-oxides. Keywords: aromatic N-oxides; C–H···π Interactions; ditopic receptors; endo/exo complexation; host–guest chemistry; resorcinarenes; Introduction Resorcinarenes are macrocyclic compounds with a bowl-shaped cavity stabilised by circular

• intramolecular O···H–O hydrogen bonds (HBs) [1][2]. The combination of their confined cavity and conformational flexibility has driven the interest in these synthetic receptors [3], a subclass of calixarenes [4], for a wide range of applications in fields such as catalysis [5][6][7][8][9], sensors [10][11

Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• potentially increases the tumor selectivity of drugs and decreases their cardiotoxicity. Increased expression of gonadotropin-releasing hormone (GnRH) receptors on the surface of tumor cells has been reported. Thus, the attachment of the aforementioned chemotherapeutic drugs to GnRH-based peptides may result

• the first step in the hypothalamus-pituitary-gonadal axis, which plays an important role in reproduction [1]. It has been reported that gonadotropin-releasing hormone receptors (GnRH-Rs) are highly expressed on the surface of tumor cells, especially in gynaecological malignant tumors (breast, ovarian

• . Small peptides that recognize target receptors on tumor cells might be suitable targeting moieties for this purpose. Hormone peptides, in particular, GnRH and somatostatin derivatives that possess antiproliferative effect on their own, are among the best candidates as homing peptides [10]. A.V. Schally

A conformationally adaptive macrocycle: conformational complexity and host–guest chemistry of zorb[4]arene

• Liu-Pan Yang,
• Song-Bo Lu,
• Arto Valkonen,
• Fangfang Pan,
• Kari Rissanen and
• Wei Jiang

Beilstein J. Org. Chem. 2018, 14, 1570–1577, doi:10.3762/bjoc.14.134

• , Wuhan, 430079, China 10.3762/bjoc.14.134 Abstract Large amplitude conformational change is one of the features of biomolecular recognition and is also the basis for allosteric effects and signal transduction in functional biological systems. However, synthetic receptors with controllable conformational

• binding behavior of ZB4 and lays the basis for the construction of stimuli-responsive materials with ZB4 as a major component. Keywords: conformations; host–guest chemistry; macrocycles; supramolecular chemistry; zorb[4]arene; Introduction Macrocyclic receptors are the principal workhorses used in

• [15][16] and signal transduction [17] observed with bioreceptors. However, similar conformationally adaptive synthetic macrocyclic receptors are relatively rare in the literature [18][19][20][21][22][23]. During the last five years, we have developed two classes of macrocyclic receptors with

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• molecules is regulated, separates the nucleus from the cytosol. Macromolecules, like proteins, gain access to the nucleus by recognition of their nuclear localization sequences (NLS) by NLS-receptors, and following energy-dependent uptake processes. Several such natural occurring protein-derived NLS have

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• estrogen receptors (ERα and ERβ) [28]. Certain derivatives of 2- or 4-aminoestrone or their 3-methyl ether possess diverse biological activities, including enzyme inhibitory or antiproliferative properties [1][2][3][29][30]. The 17β-HSD1 enzyme is responsible for the reduction of estrone into 17β-estradiol