End-group-functionalized poly(N,N-diethylacrylamide) via free-radical chain transfer polymerization: Influence of sulfur oxidation and cyclodextrin on self-organization and cloud points in water

• Sebastian Reinelt,
• Daniel Steinke and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 680–691, doi:10.3762/bjoc.10.61

• temperature are widely investigated [13]. Within this group of materials, thermosensitive water-soluble polymers, possessing a lower critical solution temperature (LCST), have attracted much attention in several studies within the last decades [13][14][15][16][17]. The nature of the end-group of a short chain

Total synthesis and cytotoxicity of the marine natural product malevamide D and a photoreactive analog

• Werner Telle,
• Gerhard Kelter,
• Heinz-Herbert Fiebig,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2014, 10, 316–322, doi:10.3762/bjoc.10.29

• 200 times less active than the natural product 1. Lower cytotoxicity may be associated with solubility problems. We will now search for more water-soluble, photoactivatable analogs of 1. Nunes and coworkers had synthesized a benzophenone-labelled derivative of the analog HTI-286, which competes with 3

Carbenoid-mediated nucleophilic “hydrolysis” of 2-(dichloromethylidene)-1,1,3,3-tetramethylindane with DMSO participation, affording access to one-sidedly overcrowded ketone and bromoalkene descendants^§

• Rudolf Knorr,
• Thomas Menke,
• Johannes Freudenreich and
• Claudio Pires

Beilstein J. Org. Chem. 2014, 10, 307–315, doi:10.3762/bjoc.10.28

• , equally intense methyl singlet signals, as expected for 10, appeared after seven hours at 100 °C. However, the usual (Et2O/water) work-up procedure did not afford any (acidic or nonacidic) organic product, which suggests that 6 or 10 were converted to water-soluble, unserviceable arenesulfonic acids that

• (ca. 0.001 M [21]) of KOH in DMSO. Granting preference to the chlorine transfer from 6 to 11, the byproduct 13 of 12 would hardly be traceable: even if 13 reacted with 11, for example, the resultant water-soluble [28] bis(sulfoxide) 16 might get lost in the usual procedure of aqueous work-up. As an

Synthesis and biological activity of N-substituted-tetrahydro-γ-carbolines containing peptide residues

• Nadezhda V. Sokolova,
• Valentine G. Nenajdenko,
• Vladimir B. Sokolov,
• Daria V. Vinogradova,
• Elena F. Shevtsova,
• Ludmila G. Dubova and
• Sergey O. Bachurin

Beilstein J. Org. Chem. 2014, 10, 155–162, doi:10.3762/bjoc.10.13

• cases affording the desired conjugates 6a–g in good yields. Next, we turned our attention to the deprotection of the amine function in the peptide residues, in order to obtain water-soluble conjugates. Thus, N-Boc protecting groups were removed from compounds 6a–g with 2 M HCl in methanol to give the

Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

• Tatyana V. Abramova,
• Olga B. Morozova,
• Vladimir N. Silnikov and
• Alexandra V. Yurkovskaya

Beilstein J. Org. Chem. 2013, 9, 2898–2909, doi:10.3762/bjoc.9.326

• experiments, has a disadvantage of a relatively low absorbance at a wavelength of 308 nm at physiological pH. As an alternative, in our investigations water soluble carboxylic derivatives of benzophenone (namely, 4-carboxy-, 3-carboxy- and 3,3’,4,4’-tetracarboxybenzophenone) were used as efficient

Oligomeric epoxide–amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties

• Julian Fischer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2803–2811, doi:10.3762/bjoc.9.315

• [5]. The Tc can be influenced for example through copolymerization with hydrophobic or hydrophilic comonomers and further through supramolecular interactions of these comonomers with cyclodextrins (CD) [6][7][8][9][10]. Generally, CDs are water soluble and their ability of forming inclusion complexes

• resins exhibit poor solubility in water [15][16][17]. Accordingly, epoxide–amine polymers are not yet deeply investigated in respect to LCST behavior [18][19]. At present, most available bio-based and water soluble epoxy resins are expensive and use petroleum-based curing agents [20]. Thus, in the

• around 1–3 thousands. Interestingly, the calculated values due to Carothers’ equation (1.2-fold excess of the amine, complete conversion) gave an average molecular weight of 1760 g/mol for 9 and 1826 g/mol for 10, respectively. Conclusion Two novel water soluble and thermoresponsive glycerol diglycidyl

3-Pyridinols and 5-pyrimidinols: Tailor-made for use in synergistic radical-trapping co-antioxidant systems

• Luca Valgimigli,
• Daniele Bartolomei,
• Riccardo Amorati,
• Evan Haidasz,
• Jason J. Hanthorn,
• Susheel J. Nara,
• Johan Brinkhorst and
• Derek A. Pratt

Beilstein J. Org. Chem. 2013, 9, 2781–2792, doi:10.3762/bjoc.9.313

• water-soluble reducing equivalent into a lipid-soluble one [5][6][7]. In recent years, some of us have worked to understand the kinetic and thermodynamic basis for synergism among radical-trapping antioxidants in homogeneous solution, which is summarized in Scheme 3 [8][9]. When two (or more

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• agent, the water-soluble tris(2-carboxyethyl)phosphine (TCEP; often prepared and used as its hydrochloride salt TCEP·HCl) can be employed [45][46][47][48][49][50][51][52][53][54][55], which is especially suitable for applications in biological systems because it also protects cysteine residues in

• (1 mol %) and TBTA (1 mol %) under aerobic conditions [64]. Cyclic voltammetry measurements have supported the hypothesis of TBTA influencing the redox activity of copper(I), as the redox potential of the Cu(I)/Cu(II) pair was shown to rise by approximately 300 mV when the water-soluble derivative

• CuAAC in the bioconjugation reaction with cowpea mosaic virus (Scheme 3) [45], water-soluble derivatives such as THPTA [70][71][72][73][74][75][76][77][78], BTTP [79], BTTAA [74], BTTES [68], and BTTPS [79] have been applied in CuAAC reactions (Figure 1). Closely related to tris(triazolylmethyl)amines

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• –Emmons reaction (HWE). The HWE reaction has many advantages over the Wittig olefination. The phosphonate anions tend to be more nucleophilic (less basic) than the corresponding phosphorous ylides. The byproducts, dialkyl phosphates are water soluble and hence easier to remove from the product compared to

Flow synthesis of a versatile fructosamine mimic and quenching studies of a fructose transport probe

• Matthew B. Plutschack,
• D. Tyler McQuade,
• Giulio Valenti and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 2022–2027, doi:10.3762/bjoc.9.238

• flow chemistry challenge. The output from the oxime step contains excess hydroxylamine and salts carried from the first step that poisoned the packed-bed catalyst we screened. In theory, continuous purification could remove these materials but existing strategies do not enable removal of water soluble

• byproducts from a water soluble product. Thus, we obtained crude 2 by simple work up: neutralization, concentration, precipitation of salts using tetrahydrofuran, filtration, concentration and dissolution in 10:1 ethanol/acetic acid. This solution was converted to amine 3 using an H-Cube (commercially

Topochemical control of the photodimerization of aromatic compounds by γ-cyclodextrin thioethers in aqueous solution

• Hai Ming Wang and
• Gerhard Wenz

Beilstein J. Org. Chem. 2013, 9, 1858–1866, doi:10.3762/bjoc.9.217

• undesirable heterogenous reaction conditions [19]. Yields of heterogenous photoreactions generally depend on the particle size of the educt phase because the penetration depth of the incident light is limited. Recently, we synthesized a series of highly water-soluble per-6-deoxy-thioethers of β- and γ-CD

• , which are able to solubilize hydrophobic, nearly insoluble guest molecules, such as camptothecin [20], 1,4-dihydroxyanthraquinone [21], betulin [22], benzene and cyclohexane derivatives [23], and even C60 [24] in water. Furthermore, their respective γ-CD thioethers form highly water-soluble 1:2

An organocatalytic route to 2-heteroarylmethylene decorated N-arylpyrroles

• Alexandre Jean,
• Jérôme Blanchet,
• Jacques Rouden,
• Jacques Maddaluno and
• Michaël De Paolis

Beilstein J. Org. Chem. 2013, 9, 1480–1486, doi:10.3762/bjoc.9.168

• presents an ideal push–pull configuration tunable with the pH by protonation of the pyridine ring. This is likely to lead to applications of 10a such as for new water-soluble molecular probes. Conclusion A new catalytic and regioselective preparation of substituted N-arylpyrroles decorated with various 2

Mild and efficient cyanuric chloride catalyzed Pictet–Spengler reaction

• Ashish Sharma,
• Mrityunjay Singh,
• Nitya Nand Rai and
• Devesh Sawant

Beilstein J. Org. Chem. 2013, 9, 1235–1242, doi:10.3762/bjoc.9.140

• under a nitrogen atmosphere. The resultant mixture was warmed at 100 °C and stirred for 8 h. The reaction mixture was poured on the bed of crushed ice to obtain the crude. The solid so obtained was filtered and washed with chilled water and 10% EtOAc/hexane solution to remove water-soluble side products

Space filling of β-cyclodextrin and β-cyclodextrin derivatives by volatile hydrophobic guests

• Sophie Fourmentin,
• Anca Ciobanu,
• David Landy and
• Gerhard Wenz

Beilstein J. Org. Chem. 2013, 9, 1185–1191, doi:10.3762/bjoc.9.133

• -β-CD 2 was often employed, because it is much more water soluble than β-CD and can also be produced on an industrial scale [29][30]. Unfortunately, hydroxypropyl-β-CD 2 is not a single pure compound but a mixture of various similar homologues and isomers [31], and does not show formation constants

• superior to native β-CD. Thus, it was desirable to work with pure β-CD derivatives showing higher affinities. We reported recently the synthesis and use of heptafunctional 6-S-substitued CD derivatives 3 and 4 (Figure 1) for the solubilization of sparingly water-soluble drugs [32][33]. These β-CD

C–C Bond formation catalyzed by natural gelatin and collagen proteins

• Dennis Kühbeck,
• Basab Bijayi Dhar,
• Eva-Maria Schön,
• Carlos Cativiela,
• Vicente Gotor-Fernández and
• David Díaz Díaz

Beilstein J. Org. Chem. 2013, 9, 1111–1118, doi:10.3762/bjoc.9.123

• implications from a metabolic perspective. Keywords: biocatalysis; carbon–carbon bond formation; gelatin; Henry reaction; protein; Introduction Gelatin is a mixture of hot-water-soluble proteins of high average molecular weights (50–100 kDa) derived primarily from collagen, which is the main naturally

Aqueous reductive amination using a dendritic metal catalyst in a dialysis bag

• Jorgen S. Willemsen,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 960–965, doi:10.3762/bjoc.9.110

• Jorgen S. Willemsen Jan C. M. van Hest Floris P. J. T. Rutjes Radboud University Nijmegen, Institute for Molecules and Materials, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands 10.3762/bjoc.9.110 Abstract Water-soluble dendritic iridium catalysts were synthesized by attaching a reactive

• related iridium complexes that are capable of performing transfer hydrogenation reactions, as has been documented by Fukuzumi et al. [28][29][30]. The water-soluble iridium catalyst 3 was prepared according to a procedure of Francis in high yield (Scheme 1) [27]. The starting material is [Cp*IrCl2]2 which

• purification by acid–base extraction afforded the amine-containing ligand 8 in 96% yield. Ligand 8 was connected to water-soluble DAB-Am dendrimers via a protocol described by Peerlings and Meijer (Scheme 3) [32]. First, a multi-isocyanate was prepared in situ by using di-tert-butyl tricarbonate (11). After

Superstructures of fluorescent cyclodextrin via click-reaction

• Arkadius Maciollek,
• Helmut Ritter and
• Rainer Beckert

Beilstein J. Org. Chem. 2013, 9, 827–831, doi:10.3762/bjoc.9.94

• opens up a wide field of modification through click chemistry with azides or thioles [6][7]. Accordingly, following our former work with mono azide modified CD, we were encouraged to combine the fluorescent hydroxythiazole dye with CD [8][9][10]. Such water soluble spectroscopically active hosts can be

• and Discussion The water-soluble fluorescent cyclodextrin was synthesized via copper-catalyzed cycloaddition (Scheme 1). The existence of the resulting product was confirmed by MALDI–TOF spectrometry, 1H NMR and IR spectroscopy. The formation of host–guest structures between the thiazole functionality

Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide

• Lena Möller,
• Christian Hess,
• Jiří Paleček,
• Yi Su,
• Axel Haverich,
• Andreas Kirschning and
• Gerald Dräger

Beilstein J. Org. Chem. 2013, 9, 270–277, doi:10.3762/bjoc.9.33

• water-soluble protein coating, which is necessary for the cell attachment. In this paper, we disclose a strategy to strongly attach ECs to TPX 2 membranes by covalent functionalization of the chemically rather inert material with a cyclic peptide, containing the RGD (arginine-glycine-asparagine) amino

Synthesis and testing of the first azobenzene mannobioside as photoswitchable ligand for the bacterial lectin FimH

• Vijayanand Chandrasekaran,
• Katharina Kolbe,
• Femke Beiroth and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2013, 9, 223–233, doi:10.3762/bjoc.9.26

• almost quantitative and the resulting (Z)-isomer is especially long-lived. Both isomers are very well water-soluble and could be independently tested as inhibitors of mannose-specific bacterial adhesion and showed an equal and high inhibitory potency in the range of the well-known high-affinity inhibitor

A chemist and biologist talk to each other about caged neurotransmitters

• Graham C.R. Ellis-Davies

Beilstein J. Org. Chem. 2013, 9, 64–73, doi:10.3762/bjoc.9.8

• genetically encoded indicators actually use the “weaknesses”. Some photolabile neurotransmitters have now been developed and are commercially available without any testing of any sort being performed. Thus, they cannot even really be called “caged”. Biologist: Is your caged transmitter "water soluble

• rings to produce photosensitivity. The simplest type of caging chromophores are quite water soluble (Table 1), but even modest derivatives can lose water solubility precipitously! With drugs this is often counteracted by adding betacyclodextrin to the formulation, and with caged compounds, a small

• our work, as long as the substrates dissolve, we are fine. All caged neurotransmitters are water soluble to some extent, so how soluble do they have to be? Biologist: We are very concerned about concentrations! But the exact amounts used always depend on the type of experiment. Routine one-photon

Influence of cyclodextrin on the solubility and the polymerization of (meth)acrylated Triton^® X-100

• Melanie Kemnitz and
• Helmut Ritter

Beilstein J. Org. Chem. 2012, 8, 2176–2183, doi:10.3762/bjoc.8.245

• RAMEB-CD The reaction of Triton® X-100 (1) with methacryloyl chloride and acryloyl chloride gave the corresponding methacrylic ester 2 [2] and acrylic ester 3, respectively. Both monomers 2 and 3 were insoluble in water, but readily formed water-soluble host–guest complexes with RAMEB-CD (4 to 7) within

• total complexation of the hydrophobic component is required to prevent the intermolecular aggregation of the coil, which results in a higher rigidity of the polymer chain. The addition of 2 equiv of RAMEB-CD to 8 leads to a water soluble polymer with a cloud point of 11 °C. For the single and double

Cyclodextrin-based nanosponges as drug carriers

• Francesco Trotta,
• Marco Zanetti and
• Roberta Cavalli

Beilstein J. Org. Chem. 2012, 8, 2091–2099, doi:10.3762/bjoc.8.235

• achieve prolonged release kinetics or a faster release. The nanosponges could be used to improve the aqueous solubility of poorly water-soluble molecules, protect degradable substances, obtain sustained delivery systems or design innovative drug carriers for nanomedicine. Keywords: controlled release

• drugs are poorly soluble in water, which hinders their clinical application. The formulation of poorly water-soluble drugs constitutes a problem that is difficult to solve. Many technological approaches have been investigated. The ability of cyclodextrins to form inclusion complexes with various

Cyclodextrin-induced host–guest effects of classically prepared poly(NIPAM) bearing azo-dye end groups

• Gero Maatz,
• Arkadius Maciollek and
• Helmut Ritter

Beilstein J. Org. Chem. 2012, 8, 1929–1935, doi:10.3762/bjoc.8.224

• techniques. Water-soluble polymers, which exhibit a lower critical solution temperature (LCST), e.g., many poly(N-alkylacrylamides), have found numerous practical applications in waterborne smart materials such as bioactive surfaces, selective bioseparation, or hyperthermia-induced drug delivery [14

Influence of intramolecular hydrogen bonds on the binding potential of methylated β-cyclodextrin derivatives

• Gerhard Wenz

Beilstein J. Org. Chem. 2012, 8, 1890–1895, doi:10.3762/bjoc.8.218

• because it additionally yields binding enthalpies and entropies [31][32]. Results Since methylated β-CD derivatives 2–6 are highly water-soluble they are well suited for ITC. The ITC titration curves for all the β-CD derivatives 1–6 were exothermic and were in accordance with a 1:1 stoichiometry of the

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• tertiary amine-modified diarylpyrrolinol-TMS ether III as a water-soluble and recyclable organocatalyst with 4-chlorobenzoic acid as cocatalyst (Scheme 5) for the synthesis of 2H-chromene derivatives 3. The electronic effect of the tertiary amine group in the modified catalyst was believed to enhance the