Effect of ring size on photoisomerization properties of stiff stilbene macrocycles

• Sandra Olsson,
• Óscar Benito Pérez,
• Magnus Blom and
• Adolf Gogoll

Beilstein J. Org. Chem. 2019, 15, 2408–2418, doi:10.3762/bjoc.15.233

• units are then attached to an n-alkanediyl linker using a Williamson ether synthesis to yield the diethers 6a–d. Finally, the stiff stilbene unit is formed by an intramolecular McMurry reaction resulting in 1a–d [25][26]. The Z-isomer is formed in huge excess in these reactions and any trace amounts of

• ). Photoisomerization Photoisomerizing the (Z)-1a–d to the (E)-1a–d isomers requires to stretch the linker. The isomerization was achieved by irradiation of a degassed solution of (Z)-1a–d in chloroform or deuterated chloroform using either a 280 or 300 nm filter (Scheme 3). The conversion was followed by UV–vis or 1H

• the noncyclic reference is presented in Figure 2. As the linker chain gets shorter the E-isomer becomes less favored. What is particularly interesting is that even with the longest chain of twelve carbons a significantly lower amount of E-isomer as compared to the reference is obtained. Clearly even a

Fluorescent phosphorus dendrimers excited by two photons: synthesis, two-photon absorption properties and biological uses

• Anne-Marie Caminade,
• Artem Zibarov,
• Eduardo Cueto Diaz,
• Aurélien Hameau,
• Maxime Klausen,
• Kathleen Moineau-Chane Ching,
• Jean-Pierre Majoral,
• Jean-Baptiste Verlhac,
• Olivier Mongin and
• Mireille Blanchard-Desce

Beilstein J. Org. Chem. 2019, 15, 2287–2303, doi:10.3762/bjoc.15.221

• having a longer linker between the fluorophore and the phenol (Scheme 5). Studies of both the dumbbell-like dendrimers of this new series with P(S)Cl2 and ammonium terminal functions revealed that the branches are less protective towards the solvents than in the previous case. Indeed, the type of solvent

Click chemistry towards thermally reversible photochromic 4,5-bisthiazolyl-1,2,3-triazoles

• Chenxia Zhang,
• Kaori Morinaka,
• Mahmut Kose,
• Takashi Ubukata and
• Yasushi Yokoyama

Beilstein J. Org. Chem. 2019, 15, 2161–2169, doi:10.3762/bjoc.15.213

• photochromic diarylethenes containing triazole groups have been reported [20][21][22][23][24][25][26][27][28][29][30][31], all of them use the triazole ring as the linker of the second functional molecule with the diarylethene core. To the best of our knowledge, no diarylethenes or terarylenes possessing the

• been used many times to connect two functional molecules. When the Ru(I)-catalyzed Huisgen reaction is employed to connect two functional molecules, the linker itself possesses the thermally reversible photochromic property. Thus, this work can open the door to the creation of promising new materials

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

• binaphthyl system and the Lewis acidic metal center facilitated the enantioselective synthesis of cyclic carbonates from epoxides. Various catalyst was screened by changing the linker length (n = 4 to 8) and nucleophilic counter anion (X = I, Cl, Br), and 16c was found to be the best catalyst for the

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

• detection of double-stranded DNA. Compounds 15a and 16a are homo-dimeric derivatives, featuring two distyryl moieties connected via a C3 (15a) or a C4 (16a) linker. In addition, we included 9 mono-styryl derivatives. Among these, compounds 17a and 18a are long-known [66][67]; however, to the best of our

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

• present the design, synthesis and biological evaluation of novel mannosylated desmuramyl peptide derivatives. Mannose was coupled to dipeptides containing a lipophilic adamantane on N- or C-terminus through a glycolyl or hydroxyisobutyryl linker. Adjuvant activities of synthesized compounds were

• synthesized and biologically evaluated [19][20][21]. The best adjuvant activity in experiments in vivo showed the ManAdTP derivative (Figure 2) which has a ᴅ-configuration at the (adamant-1-yl)glycine moiety and (R)-configuration at the hydroxyisobutyryl linker. Its activity was higher than PGM that was used

• which two series of compounds were prepared: (i) derivatives containing a glycolyl linker between mannose and dipeptide, and (ii) derivatives containing a parent (R)-hydroxyisobutyryl linker (Figure 3). In both series, positions of adamantane binding (to the N- or C-terminus) were altered in comparison

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• the resin linker in an efficient four-step procedure compatible with Fmoc-based SPPS. In the first step the Fmoc group was cleaved by treatment with 20% piperidine in DMF giving the free amino function on the resin linker. Then the resin was washed with DCM, DMF and NMP. In the next step the free

• Fmoc-Sieber-PS resin was N-methylated. Firstly, the Fmoc group was cleaved with 20% piperidine in DMF from the resin linker (3 × 10 min shaking). After washing the resin three times with DCM, DMF and 1-methyl-2-pyrrolidone (NMP), the free amino groups of the resin were o-NBS protected. A mixture of 4

Diazocine-functionalized TATA platforms

• Roland Löw,
• Talina Rusch,
• Fynn Röhricht,
• Olaf Magnussen and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1485–1490, doi:10.3762/bjoc.15.150

• coupling to a bulk gold surface via a conjugated linker over 11 bonds and 14 Å [11]. Thermal cis→trans isomerizations of azobenzenes are usually slow with half-lives of the trans-isomer within the range of hours to days at room temperature (parent azobenzene: 4–5 d at 25 °C) [12]. Rotation around the N=N

Reversible end-to-end assembly of selectively functionalized gold nanorods by light-responsive arylazopyrazole–cyclodextrin interaction

• Maximilian Niehues,
• Patricia Tegeder and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2019, 15, 1407–1415, doi:10.3762/bjoc.15.140

• assembly and disassembly of the AuNR could be induced by host–guest interaction of CD on the nanorods and a photoswitchable arylazopyrazole cross-linker in aqueous solution. The end-to-end assembly of AuNR could be effectively controlled by irradiation with UV and visible light, respectively, over four

• was only achieved when the CD ligand and the divalent azobenzene linker were premixed to generate the host–guest complex. This solution was then added to the AuNR leading to a ligand exchange preferentially at the ends and therefore to the linear arrangement of AuNR. If the AuNR were first end

• -functionalized with the CD, no assembly could be observed after addition of the divalent azobenzene linker. Moreover, the assemblies could only once be disassembled by the combination of UV irradiation and physical forces by sonication. The light-induced back-isomerization of azobenzenes did not form similar end

Synthesis of dipolar molecular rotors as linkers for metal-organic frameworks

• Sebastian Hamer,
• Fynn Röhricht,
• Marius Jakoby,
• Ian A. Howard,
• Xianghui Zhang,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1331–1338, doi:10.3762/bjoc.15.132

• dicarboxylic acid-substituted dipolar molecular rotors for the use as linker molecules in metal-organic frameworks (MOFs). The rotor molecules exhibit very low rotational barriers and decent to very high permanent, charge free dipole moments, as shown by density functional theory calculations on the isolated

• molecules. Four rotors are fluorescent in the visible region. The linker designs are based on push–pull-substituted phenylene cores with ethynyl spacers as rotational axes, functionalized with carboxylic acid groups for implementation in MOFs. The substituents at the phenylene core are chosen to be small to

• linkers in MOFs with potential applications as ferroelectric materials and for optical signal processing. Keywords: benzothiadiazole; dipolar rotor; fluorescence; large dipole moment; metal organic framework linker; Introduction Rotors are among the fundamental functional units in engineering in our

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• removed with an acid in each synthetic cycle. The exo-amino groups of nucleosides dA, dC and dG are protected with acyl groups, the nascent ODN is anchored to a solid support via a base- or nucleophile-cleavable linker, and in the most widely used phosphoramidite technology the phosphate groups are

• protected with the 2-cyanoethyl group. These protecting groups and the linker have to be cleaved under strongly basic and nucleophilic conditions. As a result, many sensitive groups including acetal, hemiacetal, vinyl ethers, enol ethers, aldehydes, esters, activated esters, thioesters, aziridines, epoxides

• as linker to enable deprotection and cleavage under milder basic conditions [32]. The palladium-labile allyl groups were also used for amino protection [33][34]. The o-nitrobenzyl function was used as linker to enable photo cleavage [34]. However, these methods are still not ideal. The phenoxyacetyl

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

• fentanyl-like domains. Analysis of the results obtained by SPR and ELISA revealed trends in antibody affinity and titers for heroin and fentanyl based on epitope size and linker location. In antinociception studies, the best performing vaccines offered comparable protection against heroin as our benchmark

• of chemically contiguous drug–hapten conjugates, we envisioned generating a series of structurally diverse heroin–fentanyl haptens with a focus on linker placement and bond distance between each drug’s chemical connections in order to probe the effect of the drug-epitope structure on eliciting an

• hoped to be silent spacers. In sum, the feasibility of a singular heroin–fentanyl vaccine would be evaluated through five spatial presentations, differentiated in Figure 2 by background color. The second consideration in our chemically contiguous hapten design was the location of the linker to the

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• bathochromic shift is observed towards the absorption at 451–473 nm (514 nm for compound 7, which is exceptionally high) and emission at 547–567 nm. The quantum yields of compounds 1–4 range between 0.21 and 0.57, for compounds 5–8 with propylene linker, the quantum yields are between 0.04–0.13. Interestingly

• . Bifunctional DAT as a cross-linker for proteins. The compound is a turn-on-probe, i.e., the fluorescence quantum yield Φ = 2% increased upon reaction with the target to Φ = 41%. High-resolution XPS of SAM 3. High-resolution XPS of SAM 7. Preparation of DAT–ALA conjugate 3 with fluorinated benzyl residue

• . Preparation of conjugate 7 consisting of fluorinated DAT and ALA moieties with an additional propylene linker unit. Spectroscopic properties of diaminoterephthalates 1–8; solvent CH2Cl2. Binding energies of the C 1s, O 1s, S 2p, N 1s, and F 1s photoemission lines of SAM 3 and SAM 7. Supporting Information

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• as the promoter (not in a catalytic amount) of a Henry reaction and obtained the product with 99% ee. Subsequently, Doyagüez et al. [17] attached L-proline to β-CD via different linkers (including a triazole linker) and used the resulting organocatalysts in an aldol reaction in water, albeit with a

Polyaminoazide mixtures for the synthesis of pH-responsive calixarene nanosponges

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

Beilstein J. Org. Chem. 2019, 15, 633–641, doi:10.3762/bjoc.15.59

• obtained material critically depend on the host monomer and the linker used, on their molar ratio and, in the case of copolymers, on the molar ratio between the parent comonomers. Therefore, by a proper choice of the components, tunability in the properties of the materials obtained can be achieved. In

• and 1031 cm−1, which can be attributed to neither the calixarene scaffold nor the polyaminoazide, whereas fingerprint signals at 1377, 1364, 1189 and 994 cm−1 can be attributed to the calixarene, and the signals at 1289 and 1116 cm−1 can be recognized as due to the linker groups In the solid state 13C

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• have already used azatryptophans to study proteins with intrinsic green and blue fluorescence [27][28]. The azaindole moiety allows a linker-less incorporation of a fluorescent label with minimal disturbance. Therefore, four fluorescent derivatives of nematophin were designed and their synthesis

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• influence of the chlorine atom in the 6-position of the indole ring (Figure 1C) was examined. Macrocycles 2a–j consist of an oxygen linker whereas 2g–j bear also a chlorine atom in the 6-position in the indole ring. Macrocycles 2k–p incorporate both a sulfur linker and the chlorine on the indole ring

• size of 15–17 atoms and an oxygen as the heteroatom linker improves the binding affinity. All the active macrocycles have a 6-chloro-substituted indole core. It is well established that at the bottom of the Try23 pocket a hydrophobic small subpocket exists which is formed by Phe86, Ile103, Leu82 and

LCST phase behavior of benzo-21-crown-7 with different alkyl chains

• Yan Deng,
• Xing Li,
• Qiao Zhang,
• Zheng Luo,
• Chengyou Han and
• Shengyi Dong

Beilstein J. Org. Chem. 2019, 15, 437–444, doi:10.3762/bjoc.15.38

• solubility. When the alkyl chains contain seven CH2 units, the crown ethers become poorly soluble in water (the solubility is lower than 0.5 mg/mL for 3e), indicating the hydrophobic effect of long alkyl chains. The nature of the linker unit is also closely related to the water solubility: in general, crown

• ) during the heating and following cooling cycle. Based on these results, it is concluded that the nature of the linker unit is very important in realizing LCST behavior. Even minor changes in the linker (from NH to O) can result in remarkable differences of thermo-responsiveness. Once the hydrophilicity

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• the type of olefin metathesis chain-growth polymerization that uses metathesis catalysts to generate polymers from cyclic olefins [38][39][40][41]. To obtain polymers functionalized with POSS in the side chain, a susceptible to the ROMP monomer connected via a suitable linker to the silsesquioxane

• the range of 1.3–1.9. The surface morphology and thermal properties of hybrids were found to be affected by the POSS macromer. TEM analysis of copolymer films revealed the presence of POSS agglomerates. An analogous macromer bearing POSS-bound via phenylene linker was used in the synthesis of a series

• a tremendous effect on the liquid crystalline behavior of the polymer. Wang has reported living ROMP of a series of monomers bearing a polymerizable norbornene dicarboxyimide group attached via an appropriate linker to 1–4 POSS units [53]. Copolymerization of POSS-bearing monomers with norbornene

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

• . This goal can be realized starting from sucrose triol 2 as shown in Figure 3. The first approach consists of a connection of the C1’-position of an intermediate aza-crown ether 12 with the secondary nitrogen atom present in a linker (route a in Figure 3). Another one (route b in Figure 3) involves a

• of derivative 12 in which the C1’ and the ring nitrogen atom might be connected to form cryptand 13 (route a; Figure 3). However, we have found that the preparation of a suitable aza-crown intermediate 12 with the secondary amine function in the linker and the properly modified C1’-position caused

• Scheme 3 can be also applied to prepare cryptands with larger cavities. This required an elongation of all three terminal positions (at C1’,C6,C6’) by a longer linker. Thus, reaction of triol 2 with bis(chloroethyl) ether provided derivative 21 in good yield. Replacement of the chlorine atoms for iodine

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• . Therefore, alternative methodologies are still demanded in order to facilitate and accelerate intermediate purifications [23][24][25]. In this context, Seeberger and co-workers developed an automated solid-phase synthesis of CS derivatives using a photolabile linker [26]. Here, we describe the exploration

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

• (Ewing`s sarcoma), MDA-MB-468, MDA-MB-231 (both breast cancer) and 184B5 (normal breast; chemically transformed) were investigated. As hoped, the toxicity of tubugi-1 was masked, with IC50 values decreased by ca. 1,000-fold compared to the free toxin. Due to intracellular linker cleavage, the cytotoxic

• ; (3) a fast and efficient but target-dependent binding, or better internalization, of the PDC into targeted cells; and (4) the efficient cleavage of the linker structure and, thereby, efficient liberation of the drug molecule from the conjugate at or within the diseased cell, resulting in an efficient

• doxorubicin as cytotoxic drugs to native NPY by using various linker chemistries. However, due to missing hY1R-selectivity and relatively weak antitumor efficacy these conjugates were found unsuitable as PDCs [38]. More recently, further approaches of hY1R-addressing PDCs for therapeutic applications have

Selective ring-opening metathesis polymerization (ROMP) of cyclobutenes. Unsymmetrical ladderphane containing polycyclobutene and polynorbornene strands

• Yuan-Zhen Ke,
• Shou-Ling Huang,
• Guoqiao Lai and
• Tien-Yau Luh

Beilstein J. Org. Chem. 2019, 15, 44–51, doi:10.3762/bjoc.15.4

• strand is 8:1. Keywords: cyclobutene; hydrolysis; linker; metathesis; norbornene; ROMP; selectivity; unsymmetrical ladderphane; Introduction Ring-opening metathesis polymerizations (ROMP) of strained cycloalkenes offer a powerful arsenal for the synthesis of polymers having a variety of fascinating

• ][8][9][10][11][12][13][14][15] or from biscyclobutene [16] linked with a range of different rigid linkers. When a flexible linker is used, bisnorbornene derivatives undergo cascade metathetical cyclopolymerization giving the corresponding polynorbornenes with hammock-like pendants [17][18

• report sequential ROMP of monomers containing both cyclobutene and norbornene moieties tethered by a linker. Results and Discussion A comparison of the reactivity of cyclobutene versus norbornene derivatives 4 and 5 in ROMP catalyzed by Grubbs I catalyst (6) In the beginning of this study, we have

The influence of the cationic carbenes on the initiation kinetics of ruthenium-based metathesis catalysts; a DFT study

• Magdalena Jawiczuk,
• Angelika Janaszkiewicz and
• Bartosz Trzaskowski

Beilstein J. Org. Chem. 2018, 14, 2872–2880, doi:10.3762/bjoc.14.266

• catalyst as well as the ease of synthesis. In 2013 Kośnik and Grela performed a study to check the influence of the length of the spacer between the NHC ligand and the onium tag, by synthesizing the tag with an eight –(CH2)– linker [26]. The authors concluded that the extension of the linker does not

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

• decreased (Table 2, entries 5–8) [59][60]. This may be related to the steric demand of the refolded β-barrel structure that fully surrounds the metal site. Additionally, the activity of catalyst Ru-6@FhuA with the shorter linker increased (Table 2, entry 6 compared to entries 7 and 8) [60]. The restricted

• the catalyst Ru-4 with the short linker, the activity of Ru-4@NB4exp dropped to TON = 3,000, even though the conjugation was almost quantitative [62]. However, this “influence” on the activity could not be transferred to the regio- and stereoselectivity of the polymer microstructure. Apart from ROMP