Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• that a release mechanism of the cytotoxin is part of the molecular architecture of the conjugate [31]. Disulfide linkers have shown to be well suited when utilizing the reducing power between extra- and intracellular milieus which results in cleavage and liberation of the drug. Mitomycin conjugates [32

Studies toward bivalent κ opioids derived from salvinorin A: heteromethylation of the furan ring reduces affinity

• Thomas A. Munro,
• Wei Xu,
• Douglas M. Ho,
• Lee-Yuan Liu-Chen and
• Bruce M. Cohen

Beilstein J. Org. Chem. 2013, 9, 2916–2924, doi:10.3762/bjoc.9.328

• ligands with a furanylmethyl substituent (Figure 3), we decided to use a short linker. As an alternative approach, bivalent ligands with much longer linkers can bind simultaneously to both protomers in a receptor dimer, allowing selective targeting of specific receptor oligomers [21]. We also sought to

• provide a suitable attachment point for such linkers based on our previous studies of C-2 alkoxymethyl ethers [22][23], which have higher tolerance to alkyl chain extension [24] than other derivatives of 1 [1]. Results Synthesis Initial attempts to form the 16-dimethylaminomethyl derivative 2 by treatment

• is thus not a promising attachment point. At the opposite extreme, the C-2 alkoxymethyl ether series is highly tolerant to alkyl chain extension. Compound 6 and the synthetic route used may prove useful for the attachment of very long linkers, as used with other scaffolds to bridge receptor dimers

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

• conjugates consisting of amino acid, nucleotide, and dye residues including linkers of different lengths (Figure 1). Target compounds 1–8 have been synthesized by the phosphotriester block liquid phase synthesis (LPS). Results and Discussion Design of model compounds Our previous studies revealed a great

Gold(I)-catalyzed hydroarylation reaction of aryl (3-iodoprop-2-yn-1-yl) ethers: synthesis of 3-iodo-2H-chromene derivatives

• Pablo Morán-Poladura,
• Eduardo Rubio and
• José M. González

Beilstein J. Org. Chem. 2013, 9, 2120–2128, doi:10.3762/bjoc.9.249

• , two facts are of mechanistic significance. First, the 2:3 ratio for a given R substituent (Scheme 4A, R = 4-Cl) can be compared for the two linkers. For the nitrogen-containing tether (X = NTs, Scheme 4A), almost exclusive formation of 2 was noticed (reaction in 1,2-dichloroethane, at rt for 24 h, [43

Polymeric redox-responsive delivery systems bearing ammonium salts cross-linked via disulfides

• Christian Dollendorf,
• Martin Hetzer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 1652–1662, doi:10.3762/bjoc.9.189

• or CL 2, or both cross-linkers (Scheme 2). Rheological measurements of cross-linked polymer discs To investigate the rheological characteristics of cross-linked polycationic hydrogels, polymer discs of poly(DEAAm-co-DMAEMA, 1:1) containing between 1.0 and 5.0 mol % of either CL 1 (samples 4), or CL 2

• (samples 5), or both cross-linkers (samples 6) were synthesized. The samples were immersed in distilled water until the equilibrium state of swelling was reached. The swollen samples were then used for oscillatory measurements using the serrated plate–plate geometry. As expected, the storage modulus G

• the enhanced affinity for interactions with water molecules leads to a better enclosure of water and therefore a higher swelling degree. Sample 6, which contains both cross-linkers, shows the lowest values for Q. This can be attributed to its overall higher content of cross-linker, compared to samples

Molecular assembly of amino acid interlinked, topologically symmetric, π-complementary donor–acceptor–donor triads

• M. B. Avinash,
• K. V. Sandeepa and
• T. Govindaraju

Beilstein J. Org. Chem. 2013, 9, 1565–1571, doi:10.3762/bjoc.9.178

• acids as linkers is due to their compactness, variable side chain functionality and sequence-specific self-assembling properties and the desire to exploit their inherent chiral information for helical assembly of electro-active molecular materials [35][36][37][38][39][40][41][42][43][44][45][46][47][48

Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• compounds that demonstrate such combined properties (Figure 1). As such we have prepared a number of biotinylated analogues, derived from 1a and 1b, containing linkers of various lengths (1 to 17 atoms) and hydrophobicities (polyethylene-, amide- and/or alkyl-containing). In addition, an amine-linked biotin

• essential that the linker be of sufficient length to enable the concomitant binding to Hsp90 and streptavidin, it is also important that it is not exceedingly long for two reasons. First, the possibility and extent of nonspecific binding increases with longer linkers. Second, longer linkers result in a

• ), despite the fact that both 1a and 1b bound Hsp90 with similar affinity (24.5 versus 26 nM for 1a and 1b, respectively). This is likely a result of increased steric crowding of the bulky isopropyl group in analogues of 1a. Second, in terms of the linkers, the carbon series appeared to have a somewhat

Spin state switching in iron coordination compounds

• Philipp Gütlich,
• Ana B. Gaspar and
• Yann Garcia

Beilstein J. Org. Chem. 2013, 9, 342–391, doi:10.3762/bjoc.9.39

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

• fluorescein R5N3 9 for analytic purposes. Supporting Information Details on the synthesis and analyses of building blocks and linkers, functionalization, biological evaluation and descriptions of analyses of TPX materials based on XPS, UV, IR and contact-angle measurements are found in Supporting Information

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• /bjoc.9.13 Abstract Automated oligosaccharide assembly requires suitable linkers to connect the first monosaccharide to a solid support. A new hydrogenolysis-labile linker that is stable under both acidic and basic conditions was designed, synthesized and coupled to different resins. Glycosylation and

• cleavage efficiencies on these functionalized solid supports were investigated, and restrictions for the choice of solid support for oligosaccharide synthesis were found. Keywords: glycosylation; hydrogenolysis; linkers; oligosaccharides; resins; solid-phase synthesis; Findings Since Bruce Merrifield

• , were introduced. To perform enzymatic reactions on a solid support, nonswelling resins (Synbeads) with large surfaces and big cavities that can be accessed even by proteins were developed [36]. For the design of linkers for oligosaccharide synthesis on solid support, several key features have to be

An improved synthesis of a fluorophosphonate–polyethylene glycol–biotin probe and its use against competitive substrates

• Hao Xu,
• Hairat Sabit,
• Gordon L. Amidon and
• H. D. Hollis Showalter

Beilstein J. Org. Chem. 2013, 9, 89–96, doi:10.3762/bjoc.9.12

• competed out with the active enzyme covalently linked to the probe, even though the concentration of added substrate is high compared to the probe. Enzymes have different kinetic properties in the same proteome sample, and a single enzyme can have different preferences for FP probes with different linkers

Chemical modification allows phallotoxins and amatoxins to be used as tools in cell biology

• Jan Anderl,
• Hartmut Echner and
• Heinz Faulstich

Beilstein J. Org. Chem. 2012, 8, 2072–2084, doi:10.3762/bjoc.8.233

• disulfide-containing linkers, which would be reduced inside the cell so as to release a defined thiol derivative of phalloidin (Table 1). Actin binding All phalloidin derivatives were tested for their affinity to muscle actin (α-actin), which is used as a model for β-actin present in nonmuscle cells. This

• been described as a method to improve the solubility of drugs, prolong their half-lives in plasma, or modulate their pharmacokinetics [35]. An effect not described to our knowledge so far is that pegylation can enhance, several hundred-fold, the penetration of a hydrophilic drug into cells. Linkers

Acylsulfonamide safety-catch linker: promise and limitations for solid–phase oligosaccharide synthesis

• Jian Yin,
• Steffen Eller,
• Mayeul Collot and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 2067–2071, doi:10.3762/bjoc.8.232

• Abstract Safety-catch linkers are useful for solid-phase oligosaccharide synthesis as they are orthogonal to many common protective groups. A new acylsulfonamide safety-catch linker was designed, synthesized and employed during glycosylations using an automated carbohydrate synthesizer. The analysis of the

• ] afforded linker 10. To support oligosaccharide synthesis, the safety-catch linker was first coupled to different resins (Scheme 2). In addition, since the activation and cleavage of safety-catch linkers is typically quite slow, a second, base-labile (Zemplén [24]) cleavage site was integrated to facilitate

• , the amount of glycosylating agent was decreased during a reaction, which resulted in the production of glycosylated linkers 21 and 22. It was evident that two unexpected reactions had occurred. First, the use of excess glycosylating agent, common practice for solid-phase-synthesis protocols, leads to

Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups

• H. Bauke Albada,
• Alina-Iulia Chiriac,
• Michaela Wenzel,
• Maya Penkova,
• Julia E. Bandow,
• Hans-Georg Sahl and
• Nils Metzler-Nolte

Beilstein J. Org. Chem. 2012, 8, 1753–1764, doi:10.3762/bjoc.8.200

• linkers, a set of peptides were prepared (Table 1 and Figure 1). These peptides were obtained after acidic cleavage of the resin-bound protected precursors, purified by preparative HPLC, and the fractions containing the desired compound in high purity were lyophilized from the prep-HPLC buffers. All these

Supramolecular hydrogels formed from poly(viologen) cross-linked with cyclodextrin dimers and their physical properties

• Yoshinori Takashima,
• Yang Yuting,
• Miyuki Otsubo,
• Hiroyasu Yamaguchi and
• Akira Harada

Beilstein J. Org. Chem. 2012, 8, 1594–1600, doi:10.3762/bjoc.8.182

• tertiary gels, which should create a new paradigm in materials science [10]. Polyrotaxanes form topological gels, because the rotor molecules, which act as cross-linkers, slide on the axial polymer chain. In contrast, chemical gels do not exhibit cross-linker slippage. Previously, there have been some

Synthesis of chiral sulfoximine-based thioureas and their application in asymmetric organocatalysis

• Marcus Frings,
• Isabelle Thomé and
• Carsten Bolm

Beilstein J. Org. Chem. 2012, 8, 1443–1451, doi:10.3762/bjoc.8.164

• additional stereogenic centers, alternative molecules with substituted ethylene linkers ((SS,SC)-18 and (RS,SC)-19) were designed. Their syntheses are outlined in Scheme 5, which also underlines the value of the highly modular preparative approach towards such compounds leading to a variety of molecules by

• on the stereochemistry-determining path despite the fact that they were relatively close to the thiourea substrate binding site. Thus, reducing molecular flexibility by incorporation of plain arenes as linkers appears to be more important than conformational fixation through additional stereogenic

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

Beilstein J. Org. Chem. 2012, 8, 915–929, doi:10.3762/bjoc.8.104

• modified monosaccharides, protecting groups, linkers, or other kinds of nonstandard residues, which are neither included in the standard residue sets nor present in the databases used by mass-fingerprinting approaches. Significantly fewer tools are available to aid the interpretation of HPLC or NMR spectra

Diarylethene-modified nucleotides for switching optical properties in DNA

• Sebastian Barrois and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2012, 8, 905–914, doi:10.3762/bjoc.8.103

• polymerase-assisted PEX and PCR experiments, an absolutely critical issue regarding the application of single C–C bonds, or ethinyl or phenylene linkers is the question of whether the canonical base-recognition complementarity is effected by the chromophore modification [42][43]. Due to the strongest

meta-Oligoazobiphenyls – synthesis via site-selective Mills reaction and photochemical properties

• Raphael Reuter and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2012, 8, 877–883, doi:10.3762/bjoc.8.99

• biphenyl restores the photoisomerization properties (Figure 1) [18][19]. In a related example by Samanta and Woolley a similar compound was presented featuring anchoring groups for biological applications (Figure 1) [20]. In another study the team of Hecht synthesized oligomers separated by alkynyl linkers

High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction

• Henning S. G. Beckmann,
• Heiko M. Möller and
• Valentin Wittmann

Beilstein J. Org. Chem. 2012, 8, 819–826, doi:10.3762/bjoc.8.91

• or three N,N’-diacetylchitobiose moieties. To connect the chitobiose moieties we chose several linkers of varying length and flexibility, which were, nevertheless, all expected to allow simultaneous binding to adjacent binding sites in a chelating fashion, thus, leading to especially effective

• '-diacetylchitobiose are 330–1000. It is interesting to note the differences induced by differing linker geometries. Here, not the most hydrophobic linkers show strongest binding but the ones that apparently promote multivalent binding most efficiently. Whereas the flexible linkers of C4 and C5 lead to β values of

• 1000 and 860, respectively, the ligands C2 and C3 with the less flexible aromatic linkers have significantly lower binding potencies (β values: 480 and 330). This observation points to the possibility that the aromatic linkers cannot adopt a strain-free conformation if the ligand binds in a chelating

Self-assembly of Ru₄ and Ru₈ assemblies by coordination using organometallic Ru(II)₂ precursors: Synthesis, characterization and properties

• Sankarasekaran Shanmugaraju,
• Dipak Samanta and
• Partha Sarathi Mukherjee

Beilstein J. Org. Chem. 2012, 8, 313–322, doi:10.3762/bjoc.8.34

• allowed the formation of the 3D cage 2c. The use of imidazole-based donor linkers in combination with organometallic half-sandwich ruthenium(II) precursors may generate a wide variety of complex molecular architectures with interesting functional properties. Experimental Materials and methods The acceptor

Fifty years of oxacalix[3]arenes: A review

• Kevin Cottet,
• Paula M. Marcos and
• Peter J. Cragg

Beilstein J. Org. Chem. 2012, 8, 201–226, doi:10.3762/bjoc.8.22

• incorporate porphyrin linkers between two oxacalix[3]arenes, but, due to the size of the porphyrins and their rigidity, only the capsular form was found [50]. Treatment with zinc(II) acetate introduced three equivalents of the metal, one for each porphyrin unit. 3.2.3 Capping the upper rim: Capping the upper

Imidazole as a parent π-conjugated backbone in charge-transfer chromophores

• Jiří Kulhánek and
• Filip Bureš

Beilstein J. Org. Chem. 2012, 8, 25–49, doi:10.3762/bjoc.8.4

• -dicarbonitrile (methylvinazene, 3) [28][29][30]. These derivatives were recently utilized as suitable precursors for the construction of various CT chromophores (see below). Y-shaped imidazole-derived chromophores Triarylimidazoles (lophines) and derivatives with larger π-linkers represent the simplest D-π-IM-(π

• nitro, dialkylamino, and hydroxy groups as acceptor and donors [13]. Whereas the imidazole- and thiazole-based chromophores 10a,b possess two extended π-linkers with the imino spacers at the imidazole C4/C5 and nitro and dimethylamino groups as acceptor and donor [15], chromophore 11 (VPDPI) represents

• derivatives 14 bearing a cyanoacrylic moiety connected to imidazole C2 by thiophene or thiazole π-linkers were recently utilized as dye-sensitized solar cells with an efficiency up to 6.3% [41]. Several similar classes of imidazole-derived push–pull compounds can be found in the literature. They were mainly

Dependency of the regio- and stereoselectivity of intramolecular, ring-closing glycosylations upon the ring size

• Patrick Claude,
• Christian Lehmann and
• Thomas Ziegler

Beilstein J. Org. Chem. 2011, 7, 1609–1619, doi:10.3762/bjoc.7.189

• 1-thio-galactosyl donor and a 4,6-O-benzylidene-glucose acceptor tethered by peptide-bond-containing linkers of variable size, in order to study systematically the parameters influencing the outcome of the intramolecular, ring-closing glycosylation step. In order to further provide a rationalization

Ratiometric fluorescent probe for enantioselective detection of D-cysteine in aqueous solution

• Xiao-bo Zhou,
• Wing-Hong Chan,
• Albert W. M. Lee and
• Chi-Chung Yeung

Beilstein J. Org. Chem. 2011, 7, 1508–1515, doi:10.3762/bjoc.7.176

• solutions. Interestingly, the probe is only slightly responsive to Hcy and GSH. Results and Discussion N-Alkylation of trans-1,2-diaminocyclohexane with a pair of 9-carboxamidoquinoline moieties through methylene linkers afforded multifunctionalized ACAQ (Figure 2). Bearing six metal ligating sites, ACAQ