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

• 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

Crystal structure of the inclusion complex of cholesterol in β-cyclodextrin and molecular dynamics studies

• Elias Christoforides,
• Andreas Papaioannou and
• Kostas Bethanis

Beilstein J. Org. Chem. 2018, 14, 838–848, doi:10.3762/bjoc.14.69

• increased safety in NPC animal models [12]. Moreover, superstructures of cyclodextrins like mono-lactose-appended β-CD [13] and biocleavable pluronic/β-CD-based polyrotaxanes [14] as well as PEG-lipid micelles (DSPE-PEG) in combination with HP-β-CD [15] have shown enhanced therapeutic effects and exhibit a

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

• for facile tuning of their properties such as size [13][74], membrane permeability [75] and stability [76]. Various copolymers have been reported for polymersome formation such as poly(ethylene glycol)-b-polystyrene (PEG-b-PS) [14][77], polystyrene-b-polyisocyanopeptide (PS-b-PIAT)[21][22] and poly(N

• 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

• in yields above 70%. Moreover, the Pd@PNIPAM nanoreactors could be easily recycled thanks to the reversible phase-transition of the polymeric brushes [112]. Que et al. reported the synthesis of gold nanoparticles (Au NPs) sheltered in PEG-PS nanogels for the reduction of 4-nitrophenol (4NP) [121

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

• as in the A549 and MDA-MB-468 (αVβ3−) cell lines (2.4–3.1 times, cf. entry 1 with entry 5 in Table 3). The cyclo[DKP-isoDGR]-α-amanitin conjugate bearing the lysosomally cleavable Val-Ala linker and a PEG-4 spacer 11 proved slightly more potent than α-amanitin in both the U87 (αVβ3+) and MDA-MB-468

• -amanitin (10) and cyclo[DKP-isoDGR]-PEG-4-Val-Ala-α-amanitin (11). Synthesis of α-amanitin-cyclo[DKP-RGD] and α-amanitin-cyclo[DKP-isoDGR] conjugates 7–10. Reagents and conditions: a) 1. glutaric anhydride, DMAP, iPr2NEt, DMF, overnight, 2. DIC, N-hydroxysuccinimide, DMF, overnight; b) di-N-succinimidyl

• -isoDGR]-PEG-4-Val-Ala-α-amanitin conjugate 11. Reagents and conditions: a) 4-pentynoic acid N-hydroxysuccinimidyl ester, iPr2NEt, DMF, overnight; b) N3-PEG-4-cyclo[DKP-isoDGR], sodium ascorbate, CuSO4·5H2O, DMF/water, rt, overnight. Inhibition of biotinylated vitronectin binding to αvβ3 and αvβ5

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

• of the desired products [34][39]. 4. Preparation of trinucleotides on soluble supports Another strategy of combining the advantages of solution chemistry and solid-phase methods is the assembly of oligonucleotides on soluble supports. Among the supports used for this purpose, polyethylene glycol (PEG

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -diazopyrazole derivative 158 with 4-substituted benzylidene-3-methyl-1H-pyrazol-5(4H)-one 159 in PEG-400. The reaction resulted in the synthesis of 6,7-dihydropyrazolo[1,5-a]pyrimidine derivatives 160 (Scheme 45). Selected compounds were studied for their interaction with calf thymus DNA using various

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• that were used for self-assembled monolayers (e.g., compound 61 [187]), polymers (PEG derivative 62 [188] or functionalized polyethylene 63 [189]) were reported. The McKenna’s procedure was also applied to prepare polyphosphonic acids as exemplified by the compounds 64 [120], 65 [190], 66 [191] and the

Solid-state mechanochemical ω-functionalization of poly(ethylene glycol)

• Michael Y. Malca,
• Pierre-Olivier Ferko,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2017, 13, 1963–1968, doi:10.3762/bjoc.13.191

• Michael Y. Malca Pierre-Olivier Ferko Tomislav Friscic Audrey Moores Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC, H3A 0B8, Canada 10.3762/bjoc.13.191 Abstract Poly(ethylene glycol) (PEG) is a linear polymer with a wide range of applications in chemical

• manufacturing, drug development and nanotechnology. PEG derivatives are being increasingly used to covalently modify small molecule and peptide drugs, as well as bioactive nanomaterials in order to improve solubility in biological serum, reduce immunogenicity, and enhance pharmacokinetic profiles. Herein we

• present the development of mechanochemical procedures for PEG functionalization without the need for bulk solvents, offering a cleaner and more sustainable alternative to existing solution-based PEG procedures. The herein presented mechanochemical procedures enable rapid and solvent-free derivatization of

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• polymeric macromolecular catalysts, e.g., PEG 200 and PEG 10000 as solid auxiliaries to enhance crystallization under LAG mechanochemical conditions in "polymer and liquid-assisted grinding" or POLAG [22][23]. While the focus in these investigations has been on the improvement of the macroscopic parameters

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• synthesis of differently substituted ketoesters 3 with good to high enantioselectivities by using just 2 mol % of the bifunctional catalyst. Very interestingly, Shi’s group very recently also reported PEG-bound derivatives of these catalysts which performed more or less equally selective for this

An efficient Pd–NHC catalyst system in situ generated from Na₂PdCl₄ and PEG-functionalized imidazolium salts for Mizoroki–Heck reactions in water

• Nan Sun,
• Meng Chen,
• Liqun Jin,
• Wei Zhao,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 1735–1744, doi:10.3762/bjoc.13.168

• Nan Sun Meng Chen Liqun Jin Wei Zhao Baoxiang Hu Zhenlu Shen Xinquan Hu College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310032, China 10.3762/bjoc.13.168 Abstract Three PEG-functionalized imidazolium salts L1–L3 were designed and prepared from commercially available

• 10,000. Keywords: aqueous homogeneous catalysis; Mizoroki–Heck reaction; Na2PdCl4; PEG-functionalized imidazolium salts; Introduction Nowadays, both increasing environmental concerns and drastic commercial competition are the driving forces to develop more sustainable and economic processes for

• activity in Mizoroki–Heck reactions with DMF as solvent [66]. With this regards, we herein report the development of a new poly(ethylene glycol, PEG) and pyridine bi-functionalized imidazolium salt L1 (Figure 1), which was employed as a water soluble NHC ligand precursor for an in situ generated Pd–NHC

2-Methyl-2,4-pentanediol (MPD) boosts as detergent-substitute the performance of ß-barrel hybrid catalyst for phenylacetylene polymerization

• Julia Kinzel,
• Daniel F. Sauer,
• Marco Bocola,
• Marcus Arlt,
• Tayebeh Mirzaei Garakani,
• Andreas Thiel,
• Klaus Beckerle,
• Tino Polen,
• Jun Okuda and
• Ulrich Schwaneberg

Beilstein J. Org. Chem. 2017, 13, 1498–1506, doi:10.3762/bjoc.13.148

• membrane of Escherichia coli (E. coli) [30]. For extraction of membrane proteins, commonly micelle-forming detergents such as sodium dodecyl sulfate (SDS), polyethylene–polyethyleneglycol (PE–PEG), sugar glycosides or polyoxyethylenes are applied [24][25][28][31][32]. SDS is an efficient detergent for

• carried out, reaching higher molecular weights and yields compared to catalysis with the micelle-forming refolding reagent PE–PEG. Minimum of MPD molecules was analyzed by molecular dynamics studies to enable refolding of SDS-denatured transmembrane protein FhuA ΔCVFtev [29]. This report aims to

• demonstrate the importance of the right choice of the membrane protein stabilizer for biohybrid catalysis. Results and Discussion For solubilizing the transmembrane protein FhuA ΔCVFtev PE–PEG and MPD were applied as stabilizing agent and phenylacetylene polymerization was performed as model reaction (Figure

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

• DCM/Et2O. In spite of several precipitations and recrystallizations, one coupling cycle could be completed in 5 hours, the stepwise coupling yield ranging from 90% to 95% and the crude PEG-bound octamer was obtained in 79% yield. The coupling of dGibu proceeded, however, in more than 100% yield, which

• tetramethylguanidine in aq dioxane [39] and aq ammonia, and purified by ion-exchange chromatography on DEAE cellulose. From 980 mg of crude PEG-octamer, 85 mg of pure lyophilized TEA salt of d(5´-TAGCGCTA-3´) was obtained. In other words, the yield of the isolation step was less than 30%. To avoid the modification of

One-pot synthesis of block-copolyrotaxanes through controlled rotaxa-polymerization

• Jessica Hilschmann,
• Gerhard Wenz and
• Gergely Kali

Beilstein J. Org. Chem. 2017, 13, 1310–1315, doi:10.3762/bjoc.13.127

• already started from a PEG α-CD pseudopolyrotaxane, but unthreading of α-CD was found to be a severe problem during polymerization, which could only be overcome by elaborate attachment of “molecular hooks” to both chain ends [30]. Furthermore, polyisoprene is advantageous for biomedical applications

Correction: Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 1136–1138, doi:10.3762/bjoc.13.112

• polysaccharide-derived CDs in the presence of PEG-200 and how the starting material composition is conferred to the CD products. Corrected Scheme 22 of the original article. Hyaluronic acid (HA) and glycine-derived CDs, suspected to be decorated in unreacted HA, allowing receptor-mediated cell uptake.

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• intracellular stability. Liz-Marzan et al. assessed the ability of glycan ligands to reduce the protein corona formation around rod-shaped AuNPs [71]. Lactose- and polyethylene glycol (PEG)-functionalized gold nanorods demonstrated similar ability in reducing the interaction with proteins, when compared to

• citrate-AuNPs. Moreover, comparing the macrophage NP uptake, the authors demonstrated that the lactose shell can prevent phagocytosis more efficiently than PEG coating. A deep knowledge of any aspect which can influence the GAuNP behavior is important to drive the correct design of the nanosystem and is

• ). By means of this sugar chips the carbohydrate−protein interactions have been analyzed and quantified in a very small volume with results confirmed by the conventional LSPR biosensors. Gibson et al. [66] designed 40 nm AuNPs capped with glyco-PEG ligands to discriminate different strains of E. coli

Aggregation behaviour of a single-chain, phenylene-modified bolalipid and its miscibility with classical phospholipids

• Simon Drescher,
• Vasil M. Garamus,
• Christopher J. Garvey,
• Annette Meister and
• Alfred Blume

Beilstein J. Org. Chem. 2017, 13, 995–1007, doi:10.3762/bjoc.13.99

• DPPC/DHPC systems [49], or for mixtures of phospholipids with other amphiphilic substances, e.g., in PEG-stabilized bilayer systems [50][51], for phospholipids with membrane scaffold proteins [52][53] or in combination with copolymers [54][55], or for DPPC in mixture with a T-shaped amphiphile [56

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• of diselenides as starting reagents, under an oxygen atmosphere and using PEG 200 as the solvent. This procedure involves the in situ generation of dialkyl diselenides through a K3PO4-assisted reaction of an alkyl selenocyanate obtained by a nucleophilic substitution reaction between KSeCN and alkyl

• of obtaining alkynyl analogues based on our methodology developed for the synthesis of vinyl selenides. We herein report the optimized reaction conditions for the one-pot and three-step synthesis of alkynyl selenides 5 using KSeCN as selenium source in PEG 200 as the solvent under an oxygen

• , we performed a screening of solvents under oxygen atmosphere (Table 1). Best yields were obtained with DMF, isopropanol or polyethylene glycol (PEG) as the solvents (Table 1, entries 1, 10, 12 and 13), whereas only moderate yields below 50% were obtained when the reaction was conducted in

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• of such compounds [17]. In clinical studies (phase I and II), the fluorinated compound mericitabine in combination with PEG-IFN and RBV was better tolerated and more effective in genotype 1 or 4 patients compared to the standard combination of Peg-IFN and RBV [18][19]. Further, the therapy of

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• glucose, this particular monosaccharide has been extensively used as an ideal carbon source for CD formation, under a range of experimental conditions. The microwave-assisted synthesis of FCDs from a glucose solution in the presence of poly(ethylene glycol)-200 (PEG-200) by Yang et al. is, to the best of

• show that the use of PEG-200, as a surface passivation agent (SPA), was crucial for favourable photoluminescence (PL) properties and QYs of up to 6.3% were achieved. The use of SPAs is among one of two main techniques that are widely employed to improve the PL properties of FCDs. SPAs are argued to

• hydrophobic red fluorescent CDs via surface passivation and polymer coating, in which hydrophilic anhydride groups of the polymer can react with PEG-diamine, via a ring-opening to afford a free acid and an amide-linked SPA, lead to water-soluble CDs ready for bio-labelling applications. The CDs were then

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• , and could be easily recovered and reused. Aryl iodides, activated aryl bromides and chlorides, and heteroaryl bromides were smoothly converted to phenols. In 2011, the Chen group developed a PEG-400-mediated protocol for the synthesis of phenols using CuI as the catalyst and KOH as the base (Scheme 14

• ) [36]. In this reaction system, non-toxic and cheap PEG-400 played a dual role as both ligand and solvent. The effective catalytic system could convert aryl iodide to phenols in high yields within 5 hours at 100 °C. The conversion of aryl bromides bearing either an electron-donating group or an

• (OAc)2-catalyzed ortho-hydroxylation of the synthesized diarylpyridines [59]. Their protocol employed oxone as oxidant, allowing the conversion to complete within 2 hours in PEG-3400/t-BuOH at 80–90 °C (Scheme 30). By employing their protocol, ortho-hydroxyarenes were predominately formed. This method

Diels–Alder reactions of myrcene using intensified continuous-flow reactors

• Christian H. Hornung,
• Miguel Á. Álvarez-Diéguez,
• Thomas M. Kohl and
• John Tsanaktsidis

Beilstein J. Org. Chem. 2017, 13, 120–126, doi:10.3762/bjoc.13.15

• the maleates 2d and 2e required up to 10 h reaction time at 140 °C to reach near-completion. The slowest reactions were observed using itaconic acid (2c) and the PEG containing acrylate 2g. Acrylic acid (2b) was selected for further study given our interest in products with surfactant properties, and

Poly(ethylene glycol)s as grinding additives in the mechanochemical preparation of highly functionalized 3,5-disubstituted hydantoins

• Andrea Mascitti,
• Massimiliano Lupacchini,
• Ruben Guerra,
• Ilya Taydakov,
• Lucia Tonucci,
• Nicola d’Alessandro,
• Frederic Lamaty,
• Jean Martinez and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 19–25, doi:10.3762/bjoc.13.3

• investigated in the presence of various poly(ethylene) glycols (PEGs), as safe grinding assisting agents (liquid-assisted grinding, LAG). A comparative study under dry-grinding conditions was also performed. The results showed that the cyclization reaction was influenced by the amount of the PEG grinding

• ) glycols (PEGs) are eco-friendly solvents [1][2], finding applications in the biomedical field and for pharmaceutical formulations [3] and catalysis [4]. PEG-based reaction media [1] are safe reaction environments, efficiently heated by microwaves [5], but their use in organic transformations activated by

• (POLAG) [8]. However, to the best of our knowledge, the systematic investigation of the influence of PEG polymers has not been reported yet for organic syntheses promoted by mechanical energy. We firstly reported the positive influence of PEG solvents as grinding agents for the mechanochemical

Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials

• Atsushi Tamura,
• Asato Tonegawa,
• Yoshinori Arisaka and
• Nobuhiko Yui

Beilstein J. Org. Chem. 2016, 12, 2883–2892, doi:10.3762/bjoc.12.287

• polyrotaxanes (PRXs) with reactive functional groups at the terminals of the axle polymers are attractive candidates for the design of supramolecular materials. Herein, we describe a novel and simple synthetic method for end-reactive PRXs using bis(2-amino-3-phenylpropyl) poly(ethylene glycol) (PEG-Ph-NH2) as

• an axle polymer and commercially available 4-substituted benzoic acids as capping reagents. The terminal 2-amino-3-phenylpropyl groups of PEG-Ph-NH2 block the dethreading of the α-CDs after capping with 4-substituted benzoic acids. By this method, two series of azide group-terminated polyrotaxanes

• simple synthesis method for end-reactive PRXs using commercially available 4-substituted benzoic acids. Typically, 4-substituted benzoic acids are unsuitable for the capping of pseudopolyrotaxanes because they are insufficiently bulky. In this study, bis(2-amino-3-phenylpropyl) poly(ethylene glycol) (PEG

Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates

• Souad Kachbi-Khelfallah,
• Maelle Monteil,
• Margery Cortes-Clerget,
• Evelyne Migianu-Griffoni,
• Jean-Luc Pirat,
• Olivier Gager,
• Julia Deschamp and
• Marc Lecouvey

Beilstein J. Org. Chem. 2016, 12, 1366–1371, doi:10.3762/bjoc.12.130

• ligands. The use of phosphonate ligands to modify the nanoparticle surface drew a lot of attention in the last years for the design of highly functional hybrid materials. Here, we report a methodology to synthesize bisphosphonates having functionalized PEG side chains with different lengths. The key step

• obtained must be stable in the various biological compartments and they must be stealthy to avoid the elimination by macrophages. For this purpose, appropriate coatings have already been reported [3][4]. Some of which consist in the NP surface modification using hydrophilic polymers (dextran, PEG) or

• past years, our group has focused its interest in the synthesis of various functionalized hydroxymethylene bisphosphonates (HMBPs) [10] and their applications in health science, especially in antitumor therapy [11][12][13]. Herein, we described the synthesis of novel bifunctional PEG-HMBP compounds in