Tanzawaic acids I–L: Four new polyketides from Penicillium sp. IBWF104-06

• Louis P. Sandjo,
• Eckhard Thines,
• Till Opatz and
• Anja Schüffler

Beilstein J. Org. Chem. 2014, 10, 251–258, doi:10.3762/bjoc.10.20

• 1 (700 mg), 2:3 cyclohexane/ethyl acetate eluted oily fraction 2 (560 mg), and 1:4 cyclohexane/ethyl acetate eluted oily fraction 3 (100 mg). Further work-up of fraction 1 by solid-phase extraction (Macherey-Nagel, Chromabond C18ec) with 1:1 acetonitrile/water generated intermediate A (600 mg) and

• , XDB-C8, 21.2 × 150 mm, 5 µm, 21 mL/min, isocratic conditions, 7:13 acetonitrile/0.1% formic acid). Fraction 3 was applied onto a solid-phase extraction column (Macherey-Nagel, Chromabond C18ec) and extraction with 2:3 acetonitrile/0.1% formic acid gave intermediate D (87 mg) which was used for

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

• strategy for obtaining the model conjugates should provide a synthetic versatility, easy scaling up, and high purity of the title compounds. Although there is a number of well-developed methods of the automatic solid phase supported synthesis (SPSS) of oligonucleotide–peptide conjugates [8], this strategy

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

• Huisgen’s azide–alkyne cycloaddition (CuAAC reaction). In fact, the catalytic effect of copper ions had first been mentioned by L’Abbé in 1984 [7], but had henceforth been overlooked until Meldal presented a copper(I)-catalyzed solid-phase synthesis of 1,2,3-triazoles. In this procedure, the terminal alkyne

• structure of the catalytically active species is unknown. For the solid-phase synthesis of peptidotriazoles, the group of Meldal used copper(I) iodide in combination with DIPEA (Scheme 5). The author pointed out that albeit copper(I) iodide was used in stoichiometric amounts (2 equivalents), this was only

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• , 14195 Berlin, Germany 10.3762/bjoc.9.276 Abstract We present the solid phase synthesis of carbohydrate-functionalized oligo(amidoamines) with different functionalization patterns utilizing a novel alphabet of six differently glycosylated building blocks. Highly efficient in flow conjugation of

• thioglycosides to a double-bond presenting diethylentriamine precursor is the key step to prepare these building blocks suitable for fully automated solid-phase synthesis. Introduction of the sugar ligands via functionalized building blocks rather than postfunctionalization of the oligomeric backbone allows for

• heteromultivalent glycosylation patterns by combining building blocks presenting different mono- and disaccharides. Keywords: continuous flow; flow chemistry: flow synthesis; glycoligands; multivalency; photochemistry; solid-phase synthesis; thiol–ene; thioglycosides; Introduction Multivalent carbohydrate ligand

Non-cross-linked polystyrene-supported 2-imidazolidinone chiral auxiliary: synthesis and application in asymmetric alkylation reactions

• Quynh Pham Bao Nguyen and
• Taek Hyeon Kim

Beilstein J. Org. Chem. 2013, 9, 2113–2119, doi:10.3762/bjoc.9.248

• solid phase and solution phase synthesis, non-cross-linked soluble polymer supports have attracted great interest because of some advantages such as high reactivity, easy analysis and purification of products [6][7][8][9][10][11][12]. Asymmetric alkylation reactions using polymer-supported chiral

• ]. Additionally, in the solid phase asymmetric alkylation reactions, in which Evans' 2-oxazolidinone chiral auxiliaries were used, the yield and stereoselectivity were too dependent on the base, reaction time, and supported resins. As an example, the base-catalyzed epimerization of the chiral center was

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

• Holger Erdbrink,
• Elisabeth K. Nyakatura,
• Susanne Huhmann,
• Ulla I. M. Gerling,
• Dieter Lentz,
• Beate Koksch and
• Constantin Czekelius

Beilstein J. Org. Chem. 2013, 9, 2009–2014, doi:10.3762/bjoc.9.236

• synthesis of (2S,3S)-5,5,5-trifluoroisoleucine (L-5-F3Ile) and (2R,3S)-5,5,5-trifluoro-allo-isoleucine (D-5-F3-allo-Ile) was developed. The hydrophobicity of L-5-F3Ile was examined and it was incorporated into a model peptide via solid phase peptide synthesis to determine its α-helix propensity. The α-helix

• [14][15]. Therefore, the preparation of enantiomerically pure fluorinated isoleucine analogues with retained α-helix propensity is of general interest for site-specific modification of coiled-coil positions in parallel packing arrangements, especially when solid phase peptide synthesis is employed

• peptide (KX), its α-helix propensity can be calculated from circular dichroism (CD) spectroscopy [8][9]. Therefore, 5-F3Ile was converted into its Fmoc analogue and subsequently used in solid-phase synthesis of K-5-F3Ile applying standard Fmoc-based chemistry (see Supporting Information File 1) [30]. The

One-step synthesis of pyridines and dihydropyridines in a continuous flow microwave reactor

• Mark C. Bagley,
• Vincenzo Fusillo,
• Robert L. Jenkins,
• M. Caterina Lubinu and
• Christopher Mason

Beilstein J. Org. Chem. 2013, 9, 1957–1968, doi:10.3762/bjoc.9.232

• chemistry [1], colloidal science [2], natural product chemistry [3], medicinal chemistry [4][5][6], solid-phase peptide synthesis [7] and in the biosciences [8]. Despite the many advantages of this heating method, and the introduction of a wide range of instrumentation [1], the scale up of microwave

[3 + 2]-Cycloadditions of nitrile ylides after photoactivation of vinyl azides under flow conditions

• Stephan Cludius-Brandt,
• Lukas Kupracz and
• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1745–1750, doi:10.3762/bjoc.9.201

• the first photochemical transformation of vinyl azides to pyrrole derivatives under continuous-flow conditions. Only recently, we reported the two-step preparation of vinyl azides 1 in mircrostructured flow reactors starting from alkenes 6, using the solid-phase bound iodine azide transfer-reagent 7

• further generalization of this flow protocol along with telescoping it with vinyl azide formation. Formation of azirines 2 from vinyl azides 1, photoinduced ring-opening to the nitrile ylides 3, and 1,3-dipolar cycloaddition to the pentacyclic N-heterocycles 5. Solid-phase assisted synthesis of vinyl

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• with various solid-phase Brønsted acid catalysts in supercritical carbon dioxide (Figure 7), Poliakoff and co-workers studied the effect of varying the concentration of the organic reagent in the liquid CO2 solvent [46]. The high pressures required (100–400 bar) stipulated the use of a sealed reaction

Isotopically labeled sulfur compounds and synthetic selenium and tellurium analogues to study sulfur metabolism in marine bacteria

• Nelson L. Brock,
• Christian A. Citron,
• Claudia Zell,
• Martine Berger,
• Irene Wagner-Döbler,
• Jörn Petersen,
• Thorsten Brinkhoff,
• Meinhard Simon and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 942–950, doi:10.3762/bjoc.9.108

• ) were used in feeding experiments with the Roseobacter clade members Phaeobacter gallaeciensis DSM 17395 and Ruegeria pomeroyi DSS-3, and their volatile metabolites were analyzed by closed-loop stripping and solid-phase microextraction coupled to GC–MS. Feeding experiments with [2H6]DMSP resulted in the

• by solid-phase microextraction (SPME) and by CLSA. The obtained headspace extracts were subsequently analyzed by GC–MS, leading to the identification of the volatiles dimethyl disulfide (1), dimethyl trisulfide (2), S-methyl methanethiosulfonate (3), dimethyl telluride (4), dimethyl telluryl sulfide

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• propagating building block, DEAD and triphenylphosphine was used. In general, the crude product was directly deacetylated. At each stage, the required fluorous-tagged product was isolated by fluorous-solid-phase extraction (F-SPE), and its purity determined by analysis by 500 MHz 1H NMR spectroscopy. These

From bead to flask: Synthesis of a complex β-amido-amide for probe-development studies

• Kevin S. Martin,
• Cristian Soldi,
• Kellan N. Candee,
• Hiromi I. Wettersten,
• Robert H. Weiss and
• Jared T. Shaw

Beilstein J. Org. Chem. 2013, 9, 260–264, doi:10.3762/bjoc.9.31

• the discovery of new small-molecule probes that modulate biological phenomena [1]. Although the use of solid-phase, split-pool combinatorial synthesis for the preparation of solutions of small-molecule libraries has declined, the use of these compounds for on-bead screening has resulted in recent

Efficient synthesis of phenylene-ethynylene rods and their use as rigid spacers in divalent inhibitors

• Francesca Pertici,
• Norbert Varga,
• Arnoud van Duijn,
• Matias Rey-Carrizo,
• Anna Bernardi and
• Roland J. Pieters

Beilstein J. Org. Chem. 2013, 9, 215–222, doi:10.3762/bjoc.9.25

• 24 is a mimic for DC-SIGN inhibition and its bioactivity will be tested elsewhere. Inhibition studies The inhibitory potency of 22 for LecA was studied in an ELISA type assay by using a glycochip as the solid phase [10]. In this assay an IC50 value of 0.9 μM was determined (Table 1). This compared

Inclusion of the insecticide fenitrothion in dimethylated-β-cyclodextrin: unusual guest disorder in the solid state and efficient retardation of the hydrolysis rate of the complexed guest in alkaline solution

• Dyanne L. Cruickshank,
• Natalia M. Rougier,
• Raquel V. Vico,
• Susan A. Bourne,
• Elba I. Buján,
• Mino R. Caira and
• Rita H. de Rossi

Beilstein J. Org. Chem. 2013, 9, 106–117, doi:10.3762/bjoc.9.14

• interpret as a minor solid–solid phase change, based on supporting hot stage microscopic (HSM) observations that show the initially colourless crystals turning opaque in this temperature region. A significantly larger endotherm follows at 158 °C accompanying the major phase of guest loss, while the broad

• its volatility (and hence toxicity) by conversion of the liquid pesticide into a solid phase. Experimental The compounds used in this study were purified as indicated before [6]. Crystal preparation and X-ray diffraction analysis Fenitrothion (1, 20 mg, ~0.072 mmol) was added to a saturated aqueous

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

• 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

• introduced the concept of solid-phase peptide synthesis in 1963 [1], synthesis on solid supports has evolved as a powerful tool for organic chemists [2]. Over the past fifty years this strategy has been successfully applied to the synthesis of other biopolymers, such as oligonucleotides [3] and

• oligosaccharides [4]. Solid-phase synthesis is performed on insoluble supports that are functionalized with a linker that connects the growing molecule with the resin (Scheme 1). Once the target molecule has been assembled, it is cleaved from the solid support. The solid-phase paradigm allows for the use of excess

Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

• Daniel Fürniss,
• Timo Mack,
• Frank Hahn,
• Sidonie B. L. Vollrath,
• Katarzyna Koroniak,
• Ute Schepers and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 56–63, doi:10.3762/bjoc.9.7

• either polyamines or peptoids. In addition, functionalized nucleic acids were attached to polyamines via the same route. Based on a modular solid-phase synthesis of peralkynylated peptoids with up to six alkyne groups, the latter were modified with azidosugar building blocks by using copper-catalyzed

• azide alkyne cycloadditions. In addition, the up-scaling of some particular azide-modified sugars is described. Keywords: click chemistry; glycans; peptoids; polyalkynes; polyamines; solid-phase chemistry; Introduction To date, oligosaccharides have gained more and more interest as potential drugs in

• functionalities. For peptoids, CuAAC has already been used successfully to introduce diverse side-chain functionalities directly during solid-phase synthesis of peptoids starting from both, azido- and alkyne-functionalized side chains [41][42]. In addition CuAAC has also been used in order to constrain peptoid

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• [28], as catalytic reagents for silylation of alcohols, phenols, and thiols using hexamethyldisilazane [29], in conversion of urazoles to triazolinediones [30], and in oxidation of 1,3,5-trisubstituted pyrazolines [31]. Molecular sieves have been used as solid-phase catalysts in the preparation of 2

S-Fluorenylmethyl protection of the cysteine side chain upon N^α-Fmoc deprotection

• Johannes W. Wehner and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2012, 8, 2149–2155, doi:10.3762/bjoc.8.242

• ]. This is an attractive concept, because it can be combined with solid-phase peptide synthesis (SPPS) [4][5], as well as with native chemical ligation (NCL) utilizing an S→N acyl shift [3][6][7][8][9][10]. In addition, glycocysteine derivatives can be easily converted into the corresponding dimers by

Multivalent display of the antimicrobial peptides BP100 and BP143

• Imma Güell,
• Rafael Ferre,
• Kasper K. Sørensen,
• Esther Badosa,
• Iteng Ng-Choi,
• Emilio Montesinos,
• Eduard Bardají,
• Lidia Feliu,
• Knud J. Jensen and
• Marta Planas

Beilstein J. Org. Chem. 2012, 8, 2106–2117, doi:10.3762/bjoc.8.237

• , acylation of the secondary nitrogen with Fmoc-Leu-OH was mediated by N,N’-diisopropylcarbodiimide (DIPCDI) with microwave heating at 60 °C. Peptide chain elongation followed standard 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase chemistry. After chain assembly was completed, peptides were released from the

• , USA) at 25 °C. Spectra were obtained in a fused quartz cell with 1 mm path length over a wavelength range 190–260 nm at 0.1 nm intervals, 50 nm/min speed, 0.5 s response time, and 1 nm bandwidth. Solid-phase synthesis of peptides BP100 and BP143 Peptides were synthesized manually by the solid-phase

• % purity); ESIMS (m/z): 1420.87 [M + H]+. Solid-phase synthesis of peptide aldehydes 4 and 5 TentaGel S NH2 (TG) resin (0.27 mmol/g) was placed in a syringe and swelled with CH2Cl2 (3 × 10 min) and DMF (3 × 10 min). The ortho backbone amide linker (o-BAL) was incorporated by treating the resin twice with 5

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

• phalloidin esters. Linear peptides linked to aminophalloidin Linear peptides such as Ac-Cys-Gly-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-OH (Tat peptide), and Ac-Cys-Gly-Arg8-OH (Arg8) were synthesized on an Eppendorf Ecosyn P solid-phase synthesizer by using 9-fluorenylmethoxycarbonyl (Fmoc)-Arg(Pbf)SPHB

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

• cleavage products revealed shortcomings for oligosaccharide synthesis. Keywords: glycosaminoglycans (GAGs); glycosylation; resins; safety-catch linker; solid-phase synthesis; Findings Solid-phase oligosaccharide synthesis [1][2] has been automated [3][4][5] to rapidly assemble complex oligosaccharides

• . Key to the success of solid-phase syntheses is the linker that connects the first carbohydrate building block to the solid support [6]. This linker has to remain stable throughout oligosaccharide synthesis but must be cleaved at the end of the reaction sequence to release the oligosaccharide and

Peptides presenting the binding site of human CD4 for the HIV-1 envelope glycoprotein gp120

• Julia Meier,
• Kristin Kassler,
• Heinrich Sticht and
• Jutta Eichler

Beilstein J. Org. Chem. 2012, 8, 1858–1866, doi:10.3762/bjoc.8.214

• additional cysteine residues in CD4-M5, CD4-M6 and CD4-M7, was separated from the CD4 sequences by the spacer amino acids ε-aminohexanoic acid (X) and β-alanine (B). All peptides were generated through solid-phase synthesis and purified by preparative HPLC (Figure 2 and Experimental section). Peptide binding

• , which in turn will increase their affinity to the complementary protein, and, consequently, their ability to interfere with the native protein–protein interaction. Experimental Peptide synthesis Peptides were synthesized as C-terminal amides by Fmoc/t-Bu-based solid-phase synthesis on 100 mg TentaGel S

Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery

• Jan Hoyer,
• Ulrich Schatzschneider,
• Michaela Schulz-Siegmund and
• Ines Neundorf

Beilstein J. Org. Chem. 2012, 8, 1788–1797, doi:10.3762/bjoc.8.204

• . Peptide synthesis The peptides used were synthesized as described previously [30] by automated solid-phase peptide synthesis (SPPS) on a multiple Syro II peptide synthesizer (MultiSynTech, Witten, Germany) following Fmoc/t-Bu-strategy utilizing a double-coupling procedure and in situ activation with Oxyma

• -2,6-dioxocyclohex-1-ylidene)ethyl; SPPS: solid-phase peptide synthesis; TFA: trifluoroacetic acid; TIS: triisopropylsilane; HATU: O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; DIPEA: diisopropylethylamine; TA: thioanisole; TC: p-thiocresol. Peptide sequences.a Analytical

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• , peptides containing monosaccharide-substituted allo-L- and D-threonine building blocks were assembled by solid-phase peptide synthesis (SPPS). The retro-inverso AFGP analogue contained all amino acids in D-configuration, while the allo-L-diastereomer was composed of L-amino acids, like native AFGPs, with

Automated synthesis of sialylated oligosaccharides

• Davide Esposito,
• Mattan Hurevich,
• Bastien Castagner,
• Cheng-Chung Wang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2012, 8, 1601–1609, doi:10.3762/bjoc.8.183

• sialyl α-(2→3) and α-(2→6) galactosyl imidates, which, used in combination with the automated platform, provided rapid access to a small library of conjugation-ready sialosides of biological relevance. Keywords: automated synthesis; disaccharide building blocks; solid-phase synthesis; sialic acid

• disaccharide building block approach is an attractive possibility for solid-phase synthesis, since it avoids performing a low yielding and unselective sialylation on a solid support. Here, we describe a method for the rapid preparation of different sialosides relying on a new automated solid-phase synthesis

• building blocks proved successful for the synthesis of representative Sia-containing oligosaccharides ready for biological evaluation. Results and Discussion Building-blocks preparation Many sialylation strategies utilize building blocks that require multistep syntheses [10]. In contrast, solid-phase