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

• benzene ring as a linker and their activities in copolymerization reactions. The dinuclear cobalt complexes showed a higher catalytic activity for the copolymerization of propylene oxide with phthalic anhydride than the corresponding mononuclear cobalt–salen complex and achieved one of the highest

• alternating copolymerization of epoxides with cyclic anhydrides using dinuclear cobalt–salen complexes with a benzene linker. The substituents on the salen moieties, an axial ligand on the cobalt center, and a combination of the absolute configuration of the two cobalt–salen moieties were found to have a

• catalytic activity than the corresponding mononuclear cobalt–salen complex. These results indicate that the design based on di- or multinuclear metal complexes is a promising strategy for the development of highly active catalysts. Our future studies will focus on the optimization of linker structures as

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• . The α,α′-dibromo-p-xylene (112) was chosen as a linker because of containing the benzene rings for post-synthetic functionalization. HMP-1 (113) and HMP-1-SO3H (114) were confirmed by IR spectroscopy. The peak corresponding to the C–Br bond was not detected in the FTIR spectrum of HMP-1. The peaks at

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

• ) and CHO-β (FR +ve) cell lines and their respective competition experiments demonstrate the specificity of the newly synthesized bioconstructs for future application in fluorescent guided intra-operative imaging. Keywords: chelating linker; confocal studies; continuous synthetic process; fluorescent

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

• -libraries were designed to test the effects of lactone stereochemistry, substitution of a variety of more structurally diverse and non-native functional groups on the acyl tail (e.g., alkyl, cycloalkyl, and aryl), and alkyl linker length between the head group and these functional groups [51]. The C and E

• , is a potent inhibitor of QscR [64]. A set of other compounds containing aryl tails with large substituents (such as Br, I, and SCH3) also partially inhibit SdiA; specifically, thiolactone 16 (mBTL), which has a long (4 atom) linker between the amide and phenyl, inhibited SdiA activity by 89% with an

The design and synthesis of an antibacterial phenothiazine–siderophore conjugate

• Abed Tarapdar,
• James K. S. Norris,
• Oliver Sampson,
• Galina Mukamolova and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2018, 14, 2646–2650, doi:10.3762/bjoc.14.242

• may be an interesting candidate for siderophore conjugation. Results and Discussion Typically siderophore–antibiotic conjugates consist of a linker joining the siderophore and antibiotic components. As the target is membrane-associated NDH-2 we decided to functionalise our conjugate with a non

• -cleavable linker. A polyethylene glycol (PEG) linker was selected as PEG linkers demonstrate enhanced water solubility in comparison to alkyl chain linkers. We then had to make a decision on the position of attachment for the PEG linker to compound 1. For siderophore conjugates, it is crucial that the

• linker is attached to a position in 1 such that the antibacterial activity is not compromised. Based on previous structure–activity studies of 1 by Bate et al., whereby a methoxy group was positioned on the para-position of the phenyl ring of 1 without loss of activity, we hypothesised this may be a

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

• protein [79]. Indicated key interactions are π-stacking of Y258 with the phenoxy moiety in the tail region and a hydrogen bond formed between the Q194 side chain and the carboxamide in the linker area. Furthermore the benzimidazole core shows hydrophobic contacts with isoleucins 149 and 236. More

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

• Nisachon Khunnawutmanotham,
• Cherdchai Laongthipparos,
• Patchreenart Saparpakorn,
• Nitirat Chimnoi and
• Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

• on the chromene ring, the length of the amide linker, as well as the type and position of substituents on the benzyl group all contributed significantly to the AChE inhibitory activity. The 6,7-dimethoxy-substituted chromene ring significantly enhances the activity. An additional methylene unit of

• the linker between the amide carbonyl group and the pyridine ring led to a diminished activity. The fluorine substituent at the ortho-position on the benzyl ring provided a remarkable increase in AChE inhibition. Among the derivatives, the 2,3-difluorobenzylpyridinium compound was the most potent with

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

• covalently linked directly or through a suitable linker [1][2]. The gonadotropin-releasing hormone receptor (GnRH-R) is one of the receptors overexpressed on a wide range of tumors, and has limited expression in normal peripheral tissues [3]. The GnRH itself is a decapeptide hormone, which is responsible for

• oxime bond through an aminooxyacetyl (Aoa) linker to form different drug-containing conjugates [15][16]. Based on the enzymatic stability and capability of different Dau–GnRH-III conjugates to providing appropriate intracellular drug release [15], the oxime bond was used for coupling Dau to GnRH-III or

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• ) and hydrophobic linker (benzyl, phenethyl) has an impact on the inhibition efficiency of the tested synthetic compound against the target GMIIb enzyme. Evaluation of these derivatives revealed that benzyl is a suitable hydrophobic linker. Some of them showed a weak inhibitory activity and selectivity

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

• obtained, preliminary experiments have shown that ligand 22-H2 undergoes complex formation with various nickel and palladium salts [58]. Pyrazole-bridged bisoxazoline ligands. The synthesis of an analog of bisoxazoline ligand 16-H2 in which the naphthyridine bridge is replaced with a pyrazole linker is

• distances tend to be relatively long. Ligand 34-H3 was designed to explore the effect of a single atom linker, namely a phenoxy bridge. The tert-butyl group in the para-position was incorporated as it would likely increase the overall solubility of the ligand as well as its associated complexes. DCC

A pyridinium/anilinium [2]catenane that operates as an acid–base driven optical switch

• Sarah J. Vella and
• Stephen J. Loeb

Beilstein J. Org. Chem. 2018, 14, 1908–1916, doi:10.3762/bjoc.14.165

• . Overall, the synthesis of [2]catenane [8DB24C8]6+ required multiple steps and is outlined in Scheme 1. Two literature preparations were used to construct each of the known compounds, terphenyl linker 6 [18] and bis(pyridinium)ethane axle [5][OTf]2 [19][20], while the new benzylaniline axle 4 was prepared

• as shown from 3 [21]. Once the precursor components were synthesized, the [2]catenane was assembled in two steps. Firstly, [5][OTf]2 was reacted with ten equivalents of the bis(bromomethyl)terphenyl linker 6 in CH3CN to afford [7][OTf]4 in moderate yield. Secondly, the [2]pseudorotaxane [7DB24C8]4

A hemicryptophane with a triple-stranded helical structure

• Augustin Long,
• Olivier Perraud,
• Erwann Jeanneau,
• Christophe Aronica,
• Jean-Pierre Dutasta and
• Alexandre Martinez

Beilstein J. Org. Chem. 2018, 14, 1885–1889, doi:10.3762/bjoc.14.162

• are twisted into a triple helix with the lone pair of the amines and the amide hydrogen atoms oriented toward the cavity, while the amide oxygen atoms are oriented outwards. Intramolecular hydrogen bonding between the nitrogen of the amine function of one linker with the N–H of the amide group of

Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• reported SNS pincer Pd(II) complexes that were proposed to proceed via a Pd(II) to Pd(0) type of mechanism, on the basis of the study described in this article the coupling reaction is proposed to proceed via a Pd(II) to Pd(IV) mechanism. This suggests the effect of the chain length of the linker and the

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

• units. The global structure has an average radius of gyration Rg of 1.25 nm ± 0.1 nm. Noteworthy, the distance between the RGDfK units largely varies along the MD simulations, ranging from 10 Å to 24 Å (average at 17 Å), as estimated from the distance between equivalent carbon atoms crossing the linker

• and the cyclic pentapeptides. This large variation in the distance is due to the flexibility of the linkers between the calixarene platform and the RGDfK units, together with the many possibilities of H-bonding between: (i) oxygen atoms at C=O in the linker and the hydrogen atoms of (N–H) of arginine

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• branch-cells, (ii) basicity and conformational nature of the diaza-six-membered saturated heterocycle as linker and (iii) the global molecular shape, the resulted 4-aminophenol-based melamines displayed relevant redox properties [36] and, in some cases, selective aptitudes to produce MOFs (metal-organic

• series was examined, i.e., D-N

  NH, 4, 7a, 7b, 8 and 9 (Table 4), δH resonances of the methylene protons α-to the Nsp3 nitrogen of P-1 piperazine linker (in D-N

  NH vs 7b, 8 and 9) revealed minor fluctuations, between 2.97 and 3.15 ppm. These resonances were found much further upfield with respect to

• amides [64], no such vicinal effect created by a quaternary EWG of type >Nsp3H2+ [63] was detected in the piperazine P-1 linker of compounds 7b, 8 and 9, even in the case of the strongest proton donor, the trimesic acid (pKa = 3.12, 3.89 and 4.70). In addition, only in G-1 amino-dendron D-N

  NH the 1H

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

• guests and the four naphthalene rings of the host should still be the major driving force as mentioned above. However, it was noticed that the distances between diagonal linker oxygen atoms in the backbone of the host are slightly different for the four complexes. These interactions may be tuned by the

Hyper-reticulated calixarene polymers: a new example of entirely synthetic nanosponge materials

• Alberto Spinella,
• Marco Russo,
• Antonella Di Vincenzo,
• Delia Chillura Martino and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2018, 14, 1498–1507, doi:10.3762/bjoc.14.127

• [21][22][23][24][25][26][27]. The properties of CyNSs, in terms of physical and mechanical features, porosity, thermal stability and adsorption or release abilities, may be modulated up to a certain extent by a sensible choice of the linker unit, depending on its length and possible functionalization

• . For instance, increased porosity of the CyNS obtained has been recently claimed by the use of a rigid terephthalonitrile unit as the linker [13]. On the other hand, it has been recently shown that polyamine linkers give rise to pH-sensitive materials with tunable adsorption abilities [12]. In order to

• polymeric structure and can be subsequently subjected to further chemical transformation, opening the way to a possible post-functionalization [31]. This, in turn, largely improves the possible tunability in the properties of the materials obtained. Finally, the triazole linker present in the structure is

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• activity of specific enzymes. The connection between the payload and the linker is of crucial importance since its stability can dramatically change the release and thus, the activity of the compound. For this reason, the included functional groups were designed with the consideration to provide

• conjugation of the novel cryptophycin analogues across an appropriate linker to an antibody or peptide. Either a virtually uncleavable triazole (introduced by CuAAC) or scissile ester, carbonate, or carbamate moieties were taken into account. The synthesis of the modified unit B (Scheme 1) started with the

A survey of chiral hypervalent iodine reagents in asymmetric synthesis

• Soumen Ghosh,
• Suman Pradhan and
• Indranil Chatterjee

Beilstein J. Org. Chem. 2018, 14, 1244–1262, doi:10.3762/bjoc.14.107

• class of C2-symmetric chiral iodoarene precatalyst 8a using (−)-ethyl lactate as a chiral linker with the aromatics attached followed by its successful conversion to the amide derivative to generate precatalyst 8a [37][38]. Application of this precatalyst 8a was employed for the Kita oxidation [32] with

London dispersion as important factor for the stabilization of (Z)-azobenzenes in the presence of hydrogen bonding

• Andreas H. Heindl,
• Raffael C. Wende and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 1238–1243, doi:10.3762/bjoc.14.106

• other azobenzenes 5–7 in tert-butyl methyl ether (TBME) as solvent. This observation is surprising, since azobenzenes 4–7 are electronically very similar as the methylene linker prevents conjugation of the N-aryl and the azobenzene moieties. At first thought, the large spatial separation of the N

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

• and 10 with longer linkers exhibit relatively higher cytotoxicity in comparison to both distamycin and uramustine. The distamycin fragment directs binding to the A·T-rich sequences in the minor groove, and higher flexibility due to the longer linker allows optimal positioning of the mustard for DNA

• alkylation. In addition, longer linker imparts more lipophilicity, which in turn, favors better transportation of these compounds into the cells. Anthony et al. reported a series of short MGBs based on the lead compounds distamycin and thiazotropsins with the installation of hydrophobic aromatic head groups

• challenging tandem hairpin Py/Im polyamides which could recognize >10 base pairs with flexible linker conjugated with a fluorescent dye (either Texas Red (TR) or Cyanine 3 (Cy3)) using a Fmoc-based solid phase synthetic approach; two of the representative conjugates 23 and 24 are shown in the Figure 8 [86][87

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

• partially or completely saturated in order to get stereochemically different compounds for structure–activity determinations. The saturated derivatives contain a phenyl moiety at C-2 attached through an ethenediyl or ethanediyl linker. Of the synthesized 2- and 4-regioisomers, solely the 2-counterparts

• derivatives, bearing a lipophilic phenyl group attached to C-2 through an amino linker. In continuation of our studies with respect to cross-coupling reactions on ring A of 13α-estrone, here we disclose the development of a Pd-catalyzed C(sp2)–N coupling methodology for the transformation of 2-bromo- and 4

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

• . The general architecture of PDCs consists of three building blocks: the tumor-homing peptide, the cytotoxic agent and the biodegradable connecting linker. The aim of the current review is to provide a spherical perspective on the basic principles governing PDCs, as also the methodology to construct

• conducted via a rationally designed linker able to release the drug inside the cancer microenvironment [19]. The ideal targeting molecular device would consist of the following modules: a) the cytotoxic agent (drug), b) the transporting - drug delivery vehicle (i.e., lipid, mannan [28][29][30]), c) the

• linker tethering the transporting vehicle to the cytotoxic warhead, d) the “programmable” navigating/targeting moiety (i.e., receptor-specific ligand) and e) the “stealth” carrier (i.e., PEG) transfusing enhanced bioavailability. These modules are encoded in Figure 2A with different colors: the

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• protecting group was achieved by using 2% TFA in DCM for 6 × 4 min. The coupling of the isopropylidene protected aminooxyacetic acid [17] to the N-terminus of the linker sequence was carried out by using standard protocol DIC/HOBt coupling. The cleavage from the solid support was performed at rt in a

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• preclinical and clinical studies, was zoptarelin-doxorubicin also known as AEZS-108 (previously AN-152) [16]. The anthracycline doxorubicin was conjugated to the ε-amino group of GnRH-I-[6D-Lys] by insertion of a glutaric acid linker. The resulting ester bond can be cleaved by carboxylesterases, leading to