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

Synthesis of trifunctional cyclo-β-tripeptide templates

• Frank Stein,
• Tahir Mehmood,
• Tilman Plass,
• Javid H. Zaidi and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2012, 8, 1576–1583, doi:10.3762/bjoc.8.180

• , stability to enzymatic degradation, and ability to form intermolecular stacked tubular structures. To validate the applicability of cyclic β-tripeptides within the TASP concept, an efficient synthesis of the cyclopeptide with orthogonal functionalization of the side chains is desired. A solid-phase

• functionalization by amide bond formation. To protect the lysine side chain for selective and orthogonal amide-bond formation following the solid-phase peptide synthesis (SPPS), the protection groups fluorenylmethoxycarbonyl (Fmoc) and carbobenzyloxy (Cbz) were applied. Alteration of the amine in the third β

• protection of the primary α-amino group. Therefore, tert-butyloxycarbonyl (Boc) protection was used to mask all α-amino groups during solid-phase synthesis of the tripeptide. Synthesis of the cyclo-β-peptide scaffold The Boc protected β-amino acid building blocks for SPPS of the cyclic β-tripeptide were

A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues

• James R. Cochrane,
• Dong Hee Yoon,
• Christopher S. P. McErlean and
• Katrina A. Jolliffe

Beilstein J. Org. Chem. 2012, 8, 1344–1351, doi:10.3762/bjoc.8.154

• difficult to determine structure–activity relationships [7][8]. More recently, the solid-phase synthesis of a number of analogues of the fusaricidins has been reported. However, in all cases, the side chain 3-hydroxy group was not incorporated into the structure [9]. By total synthesis of both side-chain

• epimers (Scheme 1). While macrocyclization to give the core 2 could be performed at any of the amide or ester bonds [10], we chose to use a macrolactonization approach to enable ready access to analogues of the LI-F04a core through straightforward Fmoc solid-phase peptide synthesis of the linear

• which the D-allo-Thr protecting group was either tert-butyl or ΨMe,Me'Pro, respectively, to investigate whether a turn-inducer might assist the macrolactonization reaction. Linear peptides 5 and 6 were prepared by standard Fmoc solid-phase peptide synthesis protocols using PyBOP/Hünigs base as the

Recyclable fluorous cinchona alkaloid ester as a chiral promoter for asymmetric fluorination of β-ketoesters

• Wen-Bin Yi,
• Xin Huang,
• Zijuan Zhang,
• Dian-Rong Zhu,
• Chun Cai and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 1233–1240, doi:10.3762/bjoc.8.138

• the reaction mixture by simple fluorous solid-phase extraction (F-SPE) and used for the next round of reaction without further purification. Keywords: asymmetric fluorination; β-ketoester; fluorous cinchona ester; organocatalysis; recyclable chiral promoter; Introduction Fluorinated organic

• quinine with a fluorous acid chloride (Scheme 1). This compound was easily purified by fluorous-solid phase extraction (F-SPE) with a cartridge charged with fluorous silica gels [29][30]. It is stable in air and soluble in solvents such as CH2Cl2, CH3OH, and CH3CN. With the fluorous quinine ester C-1 in

• nonfluorous cinchona alkaloids. It can be easily recovered by simple fluorous solid-phase extraction for reuse. Experimental General Chemicals and solvents were purchased from commercial suppliers and used as received. 1H and 13C NMR spectra were recorded on a 300 MHz Varian NMR spectrometer. Chemical shifts

Photochemistry with laser radiation in condensed phase using miniaturized photoreactors

• Elke Bremus-Köbberling,
• Arnold Gillner,
• Frank Avemaria,
• Céline Réthoré and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1213–1218, doi:10.3762/bjoc.8.135

• ), power control, flow 26 mL/h. Test setup with continuously operating, miniaturized photoreactor. The miniaturized photoreactor (PEEK) during photolysis. Synthesis of carbazole (2) by photolysis. Synthesis of arylazides 2 by solid-phase synthesis. Supporting Information Supporting Information File 370

Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports

• Kerstin Knepper,
• Sylvia Vanderheiden and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1191–1199, doi:10.3762/bjoc.8.132

• distinctive structural features of indole moieties prompted us to investigate the scope and limitations of this reaction. In this paper, we describe our various strategies towards synthesis of the indole core. A solid-phase Bartoli reaction on solid supports is advantageous due to the decreased number of

• reactions have been used to expand the utility of the Bartoli solid-phase reaction. The reaction with tributyl(vinyl)tin proceeded smoothly and gave the vinylindoles in moderate yields but good purity, in four steps (Scheme 2). We also performed a couple of Suzuki reactions on solid supports. The details

• reagents and cross-coupling reactions. Although the overall yield is only moderate, due to the facile solid-phase approach, a small library of highly substituted indoles is readily available. Experimental Instrumentation and reagents: 1H NMR spectra were recorded on Bruker DP 300 (300 MHz), Bruker DP 400

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• Biology Center, 2121 Simons Drive, West Campus, Lawrence, KS 66047, USA 10.3762/bjoc.8.115 Abstract A series of substituted diaryltriazoles was prepared by a solid-phase-synthesis protocol using a modified Wang resin. The copper(I)- or ruthenium(II)-catalyzed 1,3-cycloaddition on the polymer bead allowed

• protein–protein interactions. Keywords: chemical diversity; Huisgen cycloaddition; library synthesis; peptidomimetics; solid phase synthesis; triazole; Introduction The α-helix was the first-described secondary structure of peptides discovered by Linus Pauling in 1951 [1]. With about 30% of the amino

• potential inhibitors of protein–protein interactions. Results and Discussion Synthesis of azide-functionalized Wang resins Two azide-functionalized resins were prepared for the solid-phase synthesis of diaryl-triazoles. The commercially available 4-(bromomethyl)benzoic acid (5) was converted into azide 6 in

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

• intermediate 16 yielding phosphoramidite 17. By automated DNA synthesis on a solid phase we prepared a set of four oligonucleotides in order to report preliminarily the optical properties of 4 in DNA. The sequences were identical except for the base pairs that surround the position of nucleoside 4. The

Multistep organic synthesis of modular photosystems

• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2012, 8, 897–904, doi:10.3762/bjoc.8.102

• substitution of the mixed cNDI 46 and deprotection of the red cNDI 47 gave the desired aldehyde 6. Self-organizing surface-initiated polymerization With the five building blocks 2–6 in hand, the solid-phase synthesis of photosystem 1 on ITO surfaces could be launched. ITO was first cleaned with RCA solution

• structures (Scheme 4 and Scheme 5). We thus summarize both processes in schematic form (Scheme 6). To recapitulate briefly from this perspective, we repeat that the solid-phase synthesis begins with the deposition of initiator 2 on ITO. Activation of monolayer 48 with DTT produces monolayer 49 with free

Building photoswitchable 3,4'-AMPB peptides: Probing chemical ligation methods with reducible azobenzene thioesters

• Gehad Zeyat and
• Karola Rück-Braun

Beilstein J. Org. Chem. 2012, 8, 890–896, doi:10.3762/bjoc.8.101

• for the application in ligation studies. AMPB = (aminomethylphenylazo)benzoic acid. Structure of the glycine-linked auxiliary conjugates 7 and 8. Structural differences between the trans- and the cis-state of azopeptides with a SKV PDZ binding motif. Solid-phase synthesis of the ligation-mediating

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• backbones, or mimics thereof, offer further possibilities to study protein-binding events. Keywords: glycopeptide binding; glycopeptides; glycoprotein synthesis; solid-phase peptide synthesis; synthetic vaccines; Introduction The majority of human proteins are co- or post-translationally modified by mono

• a number of cases [28][29][34]. Furthermore, several antibodies induced by the vaccines showed specific recognition of tumor cells. The MUC1 tandem repeat glycopeptides were synthesized on solid-phase, according to the Fmoc strategy, by using Fmoc protected amino acids and Fmoc glycosyl amino acid

• with a Pam3Cys TLR2 ligand connected to TN, T and sialyl-T MUC1 glycopeptides was recently described (Scheme 2) [35]. The Pam3CSK4 lipopeptide fragment 13 was prepared by Fmoc solid-phase synthesis, including protected amino-acid side chains after resin cleavage. Subsequently, different TN, T and

Investigation of the network of preferred interactions in an artificial coiled-coil association using the peptide array technique

• Raheleh Rezaei Araghi,
• Carsten C. Mahrenholz,
• Rudolf Volkmer and
• Beate Koksch

Beilstein J. Org. Chem. 2012, 8, 640–649, doi:10.3762/bjoc.8.71

• three β- and two γ-amino acids, was synthesized by standard solid-phase peptide synthesis and labeled at the N-terminus with the fluorophore 5(6)-tetramethylrhodamine (TAMRA). As described above, the chimera has a modified pentad (β- and γ-amino acids) at the center of its 31-residue sequence (positions

• solid-phase synthesis (0.05 mM scale) using a SyroXP-I peptide synthesizer (MultiSyn Tech GmbH, Witten, Germany) and HOBT/TBTU activation. Manual coupling of β- and γ-amino acids was carried out by HOAT/DIC activation. The molar excess of amino acid and coupling reagents was reduced for β- and γ

Volatile organic compounds produced by the phytopathogenic bacterium Xanthomonas campestris pv. vesicatoria 85-10

• Teresa Weise,
• Marco Kai,
• Anja Gummesson,
• Armin Troeger,
• Stephan von Reuß,
• Silvia Piepenborn,
• Francine Kosterka,
• Martin Sklorz,
• Ralf Zimmermann,
• Wittko Francke and
• Birgit Piechulla

Beilstein J. Org. Chem. 2012, 8, 579–596, doi:10.3762/bjoc.8.65

• campestris pv. vesicatoria 85-10 during growth on different media Different intensities of reactions of the three tested fungi were observed when X. c. pv. vesicatoria 85-10 was either grown on NB or NBG (Figure 1). To trace this phenomenon, we applied solid-phase micro-extraction (SPME)–GC/MS as well as PTR

• PTR–TOF–MS for the determination of exact molecular masses and assignment of atomic compositions. Regarding quantitative analysis, some striking differences between results obtained with extracts or solid-phase micro extraction (SPME) applying conventional GC/MS and PTR–MS, respectively, have been

• volatiles during incubation time, considering both qualitative and quantitative compositions of the profiles. In addition, gas-chromatographic analyses of highly volatile compounds, by using either direct headspace injection or solid-phase adsorption/thermodesorption separation on thick film capillaries

Synthesis of szentiamide, a depsipeptide from entomopathogenic Xenorhabdus szentirmaii with activity against Plasmodium falciparum

• Friederike I. Nollmann,
• Andrea Dowling,
• Marcel Kaiser,
• Klaus Deckmann,
• Sabine Grösch,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 528–533, doi:10.3762/bjoc.8.60

• synthesized using solid-phase peptide synthesis, followed by esterification and subsequent cleavage from the resin, deprotection and cyclization to yield 1, assisted by microwave irradiation at every stage with the exception of the esterification (Scheme 1). In detail, a preloaded 2-chlorotrityl chloride

• protists in order to also understand its molecular function. Experimental Synthesis Unless otherwise stated, we used the chemicals in their highest available purity. The progress of the synthesis was monitored with MALDI–MS as well as RP-UPLC coupled with ESI–MS. Solid-phase peptide synthesis. The linear

The volatiles of pathogenic and nonpathogenic mycobacteria and related bacteria

• Thorben Nawrath,
• Georgies F. Mgode,
• Bart Weetjens,
• Stefan H. E. Kaufmann and
• Stefan Schulz

Beilstein J. Org. Chem. 2012, 8, 290–299, doi:10.3762/bjoc.8.31

• studies, volatiles were collected by using solid-phase micro-extraction (SPME). Methyl phenylacetate (1), methyl p-anisate (2), methyl nicotinate (3), and o-phenylanisole (4) were emitted by pathogenic M. bovis and M. tuberculosis (Figure 1), while nontuberculous mycobacteria did not produce these four

The application of a monolithic triphenylphosphine reagent for conducting Appel reactions in flow microreactors

• Kimberley A. Roper,
• Heiko Lange,
• Anastasios Polyzos,
• Malcolm B. Berry,
• Ian R. Baxendale and
• Steven V. Ley

Beilstein J. Org. Chem. 2011, 7, 1648–1655, doi:10.3762/bjoc.7.194

• separation of the phosphine side products through its retention on the solid phase. Examination of the literature revealed that a variety of different bead supports have been used to facilitate this reaction to produce chloro-, bromo- and iodoalkanes from the corresponding alcohols [36][37][38]. However, the

• both the solution or solid-phase reactions (5% with solution-based triphenylphosphine and 18–29% with solid-supported triphenylphosphine), indicating that path B is the major pathway in either case [40][43]. Using a polystyrene-based triphenylphosphine monolith we hoped to benefit from the accelerated

Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

• Celso Almeida,
• Stefan Kehraus,
• Miguel Prudêncio and
• Gabriele M. König

Beilstein J. Org. Chem. 2011, 7, 1636–1642, doi:10.3762/bjoc.7.192

• with 5 L EtOAc yielded 5.9 g of extract, which was subjected to a VLC fractionation in an open column with silica as solid phase and a gradient solvent system with petroleum ether/acetone of 10:1, 5:1, 2:1, 1:1, 100% acetone and 100% MeOH, resulting in six VLC fractions. Compounds 1 and 3 were isolated