Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• conversion of glucose in a tandem reaction [82]. The hydrophilic block of their polymersomes was PEG, and the hydrophobic block contained both poly[2-(diethylamino)ethyl methacrylate] (PDEAEM) which is pH responsive, and poly[4-(3,4-dimethylmaleimido)butyl methacrylate] (PDMIBM) as cross-linker. The activity

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• polypeptide chain which is cleaved by a protease to give two subunits, A1 and A2, remain held together by extensive non-covalent forces and a single interchain disulfide bond [16]. The A2-subunit acts as a linker between the toxic A1-subunit and CTB which is the delivery vehicle that can transport the complex

• inhibitors Hol and Fan [46] designed and synthesised both spanning and non-spanning bivalent inhibitors. “Spanning” means the ligand has sufficient length of the linker to reach the two binding moieties of CT, whereas “non-spanning” means there is insufficient linker length for intra-pentamer chelation, but

• ]. Liu et al. synthesised bivalent ligands 16 and 17, for evaluation through biophysical techniques (Figure 7) [50]. They found that the enhancement in affinity and potency was due to non-specific interactions between the linker portion, nitrophenyl group and CT. The interactions increase as linker

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• for the use of 2’-O-RSSM-modified RNAs as prodrugs of siRNAs. Modifications at the extremities Disulfide bonds are attractive in designing drug-delivery systems. Indeed, lipophilic moieties may be attached to ONs to enhance cellular uptake. In particular, a cleavable disulfide linker has been used at

• the 3’-end of the sense strand to prepare cholesterol-conjugated siRNAs that were efficiently delivered to rat oligodendrocytes in vivo and achieved significant specific gene knockdown in these cells (Scheme 4A) [19]. The comparison with a non-cleavable alkyl linker suggests that a lipophilic siRNA

• conjugate with a disulfide linker is favorable to improve the suppression of 2’,3’-cyclic nucleotide 3’-phosphodiesterase mRNA in oligodendrocytes in vivo. This result may be attributable to increased bioavailability of siRNA in the cytoplasm. Similarly, regarding the intracellular delivery of naked peptide

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• lines, the cyclo[DKP-isoDGR]-α-amanitin conjugates bearing the lysosomally cleavable Val-Ala linker were found to be slightly more potent than α-amanitin. Apparently, for all these α-amanitin conjugates there is no correlation between the cytotoxicity and the expression of αVβ3 integrin. To determine

• disulfide linker in the cytoplasm. In another example, Perrin and co-workers conjugated the N-propargylasparagine of an amanitin analog to a cycloRGD integrin ligand (cyclo[RGDfK]) using a copper-catalyzed azide–alkyne cycloaddition [8]. The conjugates were tested in the U87 glioblastoma cell line, but only

• group (-CH2NH2) as a handle for conjugation to cytotoxic drugs (Figure 2, ligands 2 and 4) [28][29][30]. Conjugates of the functionalized ligands 2 and 4 with paclitaxel (PTX) via a 2’-carbamate with a self-immolative spacer and the lysosomally cleavable Val-Ala linker [31] were synthesized (Figure 2

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• polystyrene support decorated with a photolabile linker and its potential use for the synthesis of siRNA duplexes under mild and neutral conditions [36]. A similar strategy was used for the synthesis of partially 2'/3'-O-acetylated RNA oligonucleotides [37]. A photo-cleavable linker would also have potential

• well suited to it. Also the solution-phase synthesis of protected trinucleotide building blocks has been described in the literature [21][22][23]. In an initial attempt, thymidine as a start nucleoside was tethered to a precipitative tetrapodal soluble support via a disulfide-linker [21] (Table 1

• , the disulfide tether was replaced in a following-up study with a Q-linker (hydroquinone-O,O'-diacetic acid), to be cleaved with dilute methanolic K2CO3 for the release of trimers in fully protected form. Five different trimers were assembled at 0.5 mmol scale and released form the support as described

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

• properties of T24 revealed the HOMO and the LUMO levels are located on both the donor and acceptor part, respectively, without any contribution of the phenyl linker. Another situation was found for T25 and T26 since the LUMO predominantly extends on both the acceptor and the phenyl ring which is between the

• ° between the donor unit and the nearby phenylene linker for T29 and T30 was confirmed by quantum chemical calculations. Resulting from the almost perfect orthogonality, a good confinement of the electronic density of the two orbitals was obtained with a HOMO level predominantly located on the donor and a

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• detection of DNA by duplex [54] or triplex [69] formation have been demonstrated. Alternatively, the pyrene label can be placed onto the PNA backbone as a base replacement (in aegPNA) [55] or as a tethered label through a flexible linker (in acpcPNA) [70]. In most cases, excimer emission is predominant in

• . One promising example is the release of fluorophores by a phosphine-free photocatalyzed reduction of a self-immolative azide-based linker [105]. Single-labeled PNA probes with additional interacting partners PNA-based strand displacement probes Strand displacement probes consist of a fluorescence

• earliest PNA probes in this category are the so-called "light-up probes", which consist of a short single stranded PNA probe (ssPNA) linked to the DNA binding dye TO (Figure 18) at one end of the molecule, usually at the N-terminus, via a flexible linker [157]. The TO binds non-specifically with DNA

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• could qualify as the site of attachment of a fluorescent label without hindering the biological activity would be position 6’ of the diglucosamine backbone of lipid A. When attached to position 6’ via a linker molecule, the fluorescent label would not interfere with the binding of lipid A to the MD-2

• owing to enhanced amphiphilicity of the hybrid molecule inflicted by the hydrophobic character of the fluorescent label and the formation of aggregates which resulted in self-quenching. To circumvent these problems, a longer hydrophilic linker and a less hydrophobic fluorescent group were required. An

• elegant solution consisted in the application of glucose attached at position 6’ via a glutaryl group as a long-chain hydrophilic linker in combination with biotin or the hydrophilic fluorescent label AlexaFluor. The appropriately protected tetraacylated disaccharide 19 was subjected to treatment with Zn

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• thiol end group, which is generally attached to the reducing terminus by a linker (Figure 1a) [8][14][17][18][19][20][21][22][23][24][25][26][27]. The second method is a ligand exchange reaction involving the replacement of the ligands on pre-formed AuNPs with thiol-linked carbohydrate derivatives

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• local anesthetics: (a) a lipophilic aromatic ring, (b) an amide (or ester) linker, and (c) a terminal tertiary amine [9]. The original synthesis of these bioactive compounds involved a Perkin condensation followed by an amination reaction. An alternative pathway to AL-12B has been described by Couture

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• ′-phosphorylated trimer synthesized by standard phosphoramidite chemistry. To address the problem of m7G instability under basic conditions, the TMG-capping reaction was carried out upon deprotection of all base-labile groups. Utilization of a novel, acid labile linker to the solid support allowed for subsequent

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• preparation of acid 3 homologues (with a methylene linker between the carboxylic group and the pyrimidine ring) and their isomers resulting from two alternative regioselective pathways for the decarboxylative nucleophilic addition of malonic acid and its mono(thio)esters. Results and Discussion We first

Pyrene–nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies

• Artur Jabłoński,
• Yannic Fritz,
• Hans-Achim Wagenknecht,
• Rafał Czerwieniec,
• Tytus Bernaś,
• Damian Trzybiński,
• Krzysztof Woźniak and
• Konrad Kowalski

Beilstein J. Org. Chem. 2017, 13, 2521–2534, doi:10.3762/bjoc.13.249

• Chemistry, Biological and Chemical Research Centre, University of Warsaw, Żwirki and Wigury 101, 02-089 Warszawa, Poland 10.3762/bjoc.13.249 Abstract Fluorescent pyrene–linker–nucleobase (nucleobase = thymine, adenine) conjugates with carbonyl and hydroxy functionalities in the linker were synthesized and

• compounds. The conjugates bearing a carbonyl function represent weak emitters as compared to compounds with a hydroxy function in the linker. The self-assembly properties of pyrene nucleobases were investigated in respect to their binding to single and double strand oligonucleotides in water and in buffer

• cell. The crystallographic structure confirms that the C1-substituted pyrene is connected to the N20 atom of the thymine moiety through the 1-oxopropionyl linker. The geometry of the pyrenyl moiety deviates from planarity of 0.039 Å [28] while the average deviation from planarity for the thymine group

Synthesis and supramolecular properties of regioisomers of mononaphthylallyl derivatives of γ-cyclodextrin

• Markéta Bláhová,
• Sergey K. Filippov,
• Lubomír Kováčik,
• Jiří Horský,
• Simona Hybelbauerová,
• Zdenka Syrová,
• Tomáš Křížek and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2017, 13, 2509–2520, doi:10.3762/bjoc.13.248

• reasons. Compared to α- or β-CD, the number of publications dealing with γ-CD is quite small, e.g., [14][15]. The naphthyl group is well known for its ability to make inclusion complexes with CDs [16]. The allyl connecting linker is relatively rigid and should support the formation of supramolecular

Exploring mechanochemistry to turn organic bio-relevant molecules into metal-organic frameworks: a short review

• Vânia André,
• Sílvia Quaresma,
• João Luís Ferreira da Silva and
• M. Teresa Duarte

Beilstein J. Org. Chem. 2017, 13, 2416–2427, doi:10.3762/bjoc.13.239

• chemistry relies on the formation of intermolecular interactions between linker molecules. This combination results in 1D, 2D or 3D porous frameworks. The pore size can be adjusted by varying the size of the linkers, a modification that can be associated to the change in functional groups in the organic

• (encapsulated) as a guest within the pores of the MOF. In the second situation, the choice of the linker is crucial, as it needs to be an organic molecule listed of the generally regarded as safe (GRAS) compounds, an endogenous compound or a bioactive molecule. In both classes, the judicious choice of the

• /elimination from the body [88]. The examples given here will be separated according to the function of the APIs in the BioMOF: linker or guest. BioMOFs with active pharmaceutical ingredients (APIs) as linkers Several BioMOFs with APIs as building blocks have been synthesized recurring to mechanochemistry and

Structure–property relationships and third-order nonlinearities in diketopyrrolopyrrole based D–π–A–π–D molecules

• Jan Podlesný,
• Lenka Dokládalová,
• Oldřich Pytela,
• Adam Urbanec,
• Milan Klikar,
• Numan Almonasy,
• Tomáš Mikysek,
• Jaroslav Jedryka,
• Iwan V. Kityk and
• Filip Bureš

Beilstein J. Org. Chem. 2017, 13, 2374–2384, doi:10.3762/bjoc.13.235

• were further investigated by differential scanning calorimetry (DSC), electrochemistry, absorption and emission spectra, DFT calculations, and THG measurements. Results and Discussion Synthesis of DPP derivatives 1–5 According to the π-linker structure, two series of target chromophores a and b can be

• decompose far beyond their melting points (e.g., 2a with Tm = 244 °C and Td = 345 °C). Compounds in series b bearing an additional acetylene linker decompose almost immediately after their melting (e.g., 2b with Tm = 175 °C and Td = 189 °C). In pairs of chromophores, the substance without triple bond has an

• approximately 50 °C higher melting point (e.g., 1a/1b with Tm = 261/215 °C). Thus, the insertion of an acetylene linker decreases the melting point and causes thermal instability in the liquid phase. Derivatives 1a/2a containing a 1,4-phenylene linker showed the highest Tm and Td values of 261/244 and 330/345

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

• Satoru Mori and
• Norio Shibata

Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224

• coupling between each unit [72]. The authors noted that this intramolecular electronic coupling is likely to be dependent on the overall planarity of the molecules. Rigid TFEO-Pc dimers with a diacetylene moiety as a linker have also been reported [73][74]. There are reports of dimers via two kinds of

• diacetylene linkers, via a butadiyne and via an aryldiacetylene moiety (Figure 2). Such binuclear phthalocyanines that are connected via a rigid acetylene linker synthesized by Glaser or Sonogashira reactions have attracted attention due to their interesting effects resulting from further expansion of

• [75][76]. However, phthalocyanine dimers with high rigidity and flatness exhibit a stronger aggregation effect as π-conjugation expands. For example, a tert-butyl-substituted phthalocyanine dimer connected via diacetylene linker (9) strongly aggregates in solution although tert-butyl-substituted

Structural diversity in the host–guest complexes of the antifolate pemetrexed with native cyclodextrins: gas phase, solution and solid state studies

• Magdalena Ceborska,
• Magdalena Zimnicka,
• Aneta Aniela Kowalska,
• Kajetan Dąbrowa and
• Barbara Repeć

Beilstein J. Org. Chem. 2017, 13, 2252–2263, doi:10.3762/bjoc.13.222

• spectrum of β-CD/PTX complex (Figure 4) displays clear cross-peaks between accordingly phenyl (H7 and H8, region A), pyrrole (H4, region B), and aliphatic linker (H5-H6, region C) protons of the PTX guest with the C–H ring protons of the β-CD host (H2, H3, H4 and H5). Protons H3 and H5 of β-CD which are

Novel approach to hydroxy-group-containing porous organic polymers from bisphenol A

• Tao Wang,
• Yan-Chao Zhao,
• Li-Min Zhang,
• Yi Cui,
• Chang-Shan Zhang and
• Bao-Hang Han

Beilstein J. Org. Chem. 2017, 13, 2131–2137, doi:10.3762/bjoc.13.211

• t-plot method of PPOP-1 are smaller than those of PPOP-2 and PPOP-3. The difference between the pore volumes and BET specific surface area results of PPOPs may be related to the monomer strut length. With the shortest linker of M1, PPOP-1 possesses the lowest pore volume and BET specific surface

Complexation of molecular clips containing fragments of diphenylglycoluril and benzocrown ethers with paraquat and its derivatives

• Leonid S. Kikot',
• Catherine Yu. Kulygina,
• Alexander Yu. Lyapunov,
• Svetlana V. Shishkina,
• Roman I. Zubatyuk,
• Tatiana Yu. Bogaschenko and
• Tatiana I. Kirichenko

Beilstein J. Org. Chem. 2017, 13, 2056–2067, doi:10.3762/bjoc.13.203

• calculations show that the substitution of methyl groups in the molecule of paraquat by oxyethylene linker results in a decrease of the positive charge on the dipyridinium fragment (Figure 2) that, in turn, should lead to a reduction in the stability of the inclusion complexes of 8–10 with molecular clips 1–5

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• tethers Ziegler and co-workers investigated the use of a flexible succinoyl linker to link the glycosyl donor and acceptor counterpart. This reaction was named “intramolecular glycosylation of prearranged glycosides” [52][53]. Like in all “molecular clamp” applications, the tethering of the reaction

• modification of the macrocycle ring size, torsional rigidity of the spacer, position of the attachment to both donor and acceptor, relative configuration of hydroxy groups, and the length of the linker [58][60][61][62][63][64][65][66][67][68][69][70][71][72]. Among early examples, xylylene and phthalimido

• linker showed very high efficiency, and will be highlighted below. Another early development discussed below is the peptide-templated synthesis. Beyond these influential early studies that led to further developments, this topic was comprehensively overviewed and for early developments the reader should

β-Cyclodextrin- and adamantyl-substituted poly(acrylate) self-assembling aqueous networks designed for controlled complexation and release of small molecules

• Liang Yan,
• Duc-Truc Pham,
• Philip Clements,
• Stephen F. Lincoln,
• Jie Wang,
• Xuhong Guo and
• Christopher J. Easton

Beilstein J. Org. Chem. 2017, 13, 1879–1892, doi:10.3762/bjoc.13.183

• = 100%. Representation of ditopic complexation of an ADddn substituent of PAAADddn, by two β-CDen substituents of PAAβ-CDen through initial complexation of the adamantyl group followed by complexation of the dodecyl linker in the sequence (a) to (b) to (c). 2D NOESY 1H NMR spectrum of 0.44 wt % PAAβ

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• by Bonora et al. [37] on polyethylene glycol (PEG 5000) monomethyl ester. The overall strategy was rather similar to that of the solid-supported chemistry (Scheme 2). Accordingly, the 3´-terminal nucleoside, 5´-O-DMTr-N6-Bz-dA, was attached to the support via a 3´-succinyl linker, the 5´-O-DMTr group

• . Support loaded with longer fully protected oligomers may precipitate less quantitatively or interchain aggregation may reduce the coupling efficiency. A closely related support 6, incorporating additionally a Q-linker moiety [44], has been used for preparation of fully protected ODN trimers having only

• linker by 5 mmol L−1 K2CO3 in a 3:43:10 mixture of DCM, dioxane and MeOH (30 min), followed by neutralization with pyridinium chloride, left the 5´-O-DMTr group, 2-chlorophenyl phosphate protections and base moiety protections untouched. Silica gel chromatographic purification and conventional

Sugar-based micro/mesoporous hypercross-linked polymers with in situ embedded silver nanoparticles for catalytic reduction

• Qing Yin,
• Qi Chen,
• Li-Can Lu and
• Bao-Hang Han

Beilstein J. Org. Chem. 2017, 13, 1212–1221, doi:10.3762/bjoc.13.120

• .13.120 Abstract Porous hypercross-linked polymers based on perbenzylated monosugars (SugPOP-1–3) have been synthesized by Friedel–Crafts reaction using formaldehyde dimethyl acetal as an external cross-linker. Three perbenzylated monosugars with similar chemical structure were used as monomers in order

• temperature. Results and Discussion All the sugar-based porous organic polymers (SugPOP-1–3) were synthesized by Friedel–Crafts reaction using FDA as an external cross-linker in a similar way. The preparation routes are shown in Scheme 1. Using benzylated monosaccharides as monomers and FDA as the cross

• -linker, the Friedel–Crafts cross-linking polymerization is promoted smoothly by anhydrous FeCl3 in dry 1,2-dichloroethane (DCE). The monomers were either commercially available (Sug-1) or prepared (Sug-2 and Sug-3) by benzylation of free sugars with benzyl bromide and sodium hydride. The chemical