Silica sulfuric acid: a reusable solid catalyst for one pot synthesis of densely substituted pyrrole-fused isocoumarins under solvent-free conditions

• Sudipta Pathak,
• Kamalesh Debnath and
• Animesh Pramanik

Beilstein J. Org. Chem. 2013, 9, 2344–2353, doi:10.3762/bjoc.9.269

• starting materials, and the excellent yields of products. Keywords: green chemistry; pyrrole-fused isocoumarin; reusable solid support; silica sulfuric acid; solvent-free condition; Introduction Isocoumarins are an important class of naturally occurring lactones [1][2][3], which has attracted the

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

• for asymmetric synthesis, into the solid support [18][19]. As a part of our ongoing research, we herein report a novel NCPS-supported 2-imidazolidinone chiral auxiliary that exhibited excellent diastereocontrol. Its recycling and reuse for the synthesis of several chiral carboxylic acids are addressed

The application of a monolithic triphenylphosphine reagent for conducting Ramirez gem-dibromoolefination reactions in flow

• Kimberley A. Roper,
• Malcolm B. Berry and
• Steven V. Ley

Beilstein J. Org. Chem. 2013, 9, 1781–1790, doi:10.3762/bjoc.9.207

• immobilising the triphenylphosphine on a solid-support [48]. A polymer-supported equivalent of triphenylphosphine has also been successfully utilised by our group and by others in batch Wittig reactions [49][50], Mitsunobu and Staudinger aza-Wittig reactions [51][52], as well as many examples concerning the

• both reactions sequentially using a single monolith was investigated. It was anticipated that these studies into the interplay between the reactions might also assist to elucidate the mechanism through which the Appel reaction proceeds on solid-support. It is known that the Appel reaction can proceed

• the predominant pathway for the Appel reaction on solid-support is through intermediates 1 and 2 although overall both pathways are utilised [59]. The possibility of performing the Appel reaction following the use of the same monolith for the Ramirez gem-dibromoolefination reaction gives wider

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

• molecule to investigate Hsp90 biology, and in fact the attachment of GM to solid support enabled the identification of Hsp90 as the target of its anticancer activity through affinity purification [16]. Biotinylated GM has also been synthesized and has been proposed as a tool to identify proteins other than

• cells, 2g affinity purifies Hsp90 in complex with its regulatory cochaperones, Hsp70 and HSP-organizing protein (HOP) [1][2][13] (Figure 2f). It is important to note that the affinity purification strength of the biotinylated probes is weaker than that of directly solid-support-linked PU-H71. This is

• likely a consequence of the solid-support loading capacity. While direct attachment of a ligand to the bead can result in high local concentrations of ligand, the attachment of ligand indirectly by means of biotin-streptavidin is limited by the concentration of streptavidin available on the solid support

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

• that of the standard inhibitor methyl mannoside. These findings could be rationalised on the basis of computer-aided docking studies. The properties of the new azobenzene mannobioside have qualified this glycoside to be eventually employed on solid support, in order to fabricate photoswitchable

• -mediated bacterial adhesion in solution. On the other hand, the obtained results support the idea to immobilise the azobenzene mannobioside on a solid support to photocontrol the adhesive properties of the resulting surface. In this approach the azobenzene N=N double bond can be used as a hinge region to

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

• 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

• covalent coupling of many biomacromolecules to solid-phase-bound polycationic moieties, such as polyamines or peptoids, often requires a hydrophilic reaction environment as well as very mild cleaving conditions of the final product from the solid support. To avoid a degradation of the coupled

• d; (d) DBU (20.0 equiv), β-mercaptoethanol (20.0 equiv), DMF, rt, 18 h; (e) 1% TFA in CH2Cl2, rt, 10 min. Synthesis of spermine conjugates 20,21 and 24,25. 2-chlorotrityl chloride resin was used as a solid support. Synthesis of hexaalkynyl peptoids 26 and 27 on solid supports. Synthesis of a hexa

Iron-containing mesoporous aluminosilicate catalyzed direct alkenylation of phenols: Facile synthesis of 1,1-diarylalkenes

• Satyajit Haldar and
• Subratanath Koner

Beilstein J. Org. Chem. 2013, 9, 49–55, doi:10.3762/bjoc.9.6

• corresponding 1,1-diarylalkenes in high conversion and selectivity within a short reaction time. Furthermore, to verify whether the coupling reaction was truly catalyzed by solid Fe-Al-MCM-41 or by the leached iron species from the solid support, a “hot filtration” experiment was undertaken. A reaction between

• advantageous aspect of this type of solid-support catalyst is their scope for recycling. The reaction between phenol and phenylacetylene under optimized conditions was chosen to evaluate the recyclability of Fe-Al-MCM-41. The catalyst was separated after the completion of the reaction by simple centrifugation

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

• methods, NCL or SPPS. In addition, mannosidic glycoamino acids are of interest as ligands for mannose-specific lectins in solution [17] as well as for the fabrication of glycoarrays on solid support [10][18][19]. Moreover, we are interested to advance glycoamino acid deriatives such as 3 into ligands that

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

• method using standard Fmoc chemistry. Fmoc-Rink-MBHA resin (0.56 mmol/g) was used as a solid support. Couplings of the corresponding amino acids Fmoc-Leu-OH, Fmoc-Phe-OH, Fmoc-D-Phe-OH, Fmoc-Lys(Boc)-OH, Fmoc-Ile-OH, and Fmoc-Tyr(t-Bu)-OH (4 equiv) were performed using ethyl cyanoglyoxylate-2-oxime

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

• . 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

• features of linker 1, the amino–ester bifunctional linker, and linker 2, the safety-catch linker, to create a connection to the solid support that remains stable under conditions for cleaving temporary ester protective groups. Furthermore, the safety-catch linker should enable a variety of different

• reaction conditions on solid support since cleavage only occurs following preactivation. Thus, different modification reactions, such as Staudinger reduction, ester saponification or sulfation, necessary for the synthesis of GAGs, can be performed on solid support in an automated carbohydrate synthesizer

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

• 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

• diverse set of glycans rapidly and efficiently. The automated synthesizer proved capable of performing iterative glycosylation–deprotection cycles under conditions commonly employed for solution-phase oligosaccharide synthesis. The synthetic strategy relies on the solid support-bound linker 17 (Scheme 3

• ), which contains a latent amino spacer useful for conjugation. In addition, manual operations are minimized by performing the trichloroacetyl (TCA) reduction, ester removal and cleavage from the solid support by automation. In many cases, only hydrogenolytic cleavage of the remaining benzyl ethers and

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

• route should fulfil the requirements of (i) fast synthetic access and (ii) the possibility to attach different molecules on each side chain of the central scaffold. Here we report a new effective synthesis for cyclic β-tripeptides on a solid support, employing the oxidation-labile aryl hydrazide linker

• cyclic β-tripeptides was presented. The tripeptide scaffold was assembled completely on a solid support, thereby saving purification steps following amino acid coupling. Moreover, cleaving of the peptide from the resin and cyclization was performed in a single step employing the oxidation-labile aryl

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

• activation reagent and 2-chlorotritylchloride resin to allow cleavage of the peptide from the solid support with side-chain protecting groups intact. In the case of 6, the ΨMe,Me'Pro was introduced by coupling the known dipeptide Fmoc-Val-D-a-Thr(ΨMe,Me'Pro)-OH [18] into the growing peptide chain. While

Continuous proline catalysis via leaching of solid proline

• Suzanne M. Opalka,
• Ashley R. Longstreet and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2011, 7, 1671–1679, doi:10.3762/bjoc.7.197

• strategies involving the use of catalysts with limited solubility in flow rely on them being supported on resins or polymers (Figure 1A and B). This can be an attractive method as the catalysts are often easily recycled [20][21][22][23][24]. Finding a suitable solid support for a reaction, however, can prove

Efficient and selective chemical transformations under flow conditions: The combination of supported catalysts and supercritical fluids

• M. Isabel Burguete,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2011, 7, 1347–1359, doi:10.3762/bjoc.7.159

• anchoring of the catalytic subunit on a solid support that was either organic (polymeric) [12] or inorganic (zeolites, clays, silicas, etc.) [13]. Nevertheless, other possibilities have been also assayed. These include the use of soluble supports such as dendrimers [14][15], nanoparticles [16], soluble

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• (Scheme 32) [74]. Dodd et al. [75] have reported an efficient solid-support synthesis of 5-N-alkylamino and 5-N-arylaminopyrazoles 123. Heating the β-ketoesters 120 with resin-bound amines 119 in resin-compatible solvents, such as NMP or toluene, in the presence of DMAP gave the corresponding resin

• -immobilized β-ketoamides 121. The latter β-ketoamides 121, aryl- or alkylhydrazines and Lawesson’s reagent were suspended in a mixture of THF/Py and heated at 50–55 °C to afford resin-bound 5-aminopyrazoles 122. The free 5-aminopyrazoles 123 were liberated from the solid support by treatment with TFA (Scheme

• . Solid-support synthesis of 5-N-alkylamino and 5-N-arylaminopyrazoles. Synthesis of 5-amino-1-cyanoacetyl-3-phenyl-1H-pyrazole. Synthesis of 3-substituted 5-amino-1-aryl-4-(benzothiazol-2-yl)pyrazoles. Synthesis of 5-amino-4-carbethoxy-3-methyl-1-(4-sulfamoylphenyl)pyrazole. Synthesis of inhibitors of

Acid- mediated reactions under microfluidic conditions: A new strategy for practical synthesis of biofunctional natural products

• Katsunori Tanaka and
• Koichi Fukase

Beilstein J. Org. Chem. 2009, 5, No. 40, doi:10.3762/bjoc.5.40

• of mammalian N-glycans of the diverse structures, have motivated us to establish a practical and library-directed synthesis of the complex-type N-glycans on solid-support [32]; the initial target of our strategy is a sialic acid-containing N-glycan with asymmetric branching chains (Figure 1), which

• is difficult to obtain from natural sources. To prepare the target N-glycan as well as other diverse structures of this family in an efficient manner, we designed fragments a–d with N-phenyltrifluoroacetimidate as the leaving group, which can be efficiently glycosylated on solid-support to construct

• prominent biological activity in a “practical” and a “industrial” manner. Synthetic strategy for asparagine-linked oligosaccharide on solid support and application of microfluidic systems to fragment synthesis. β-Mannosylation using an integrated microfluidic/batch system. Yield and β/α-ratio are analyzed

Controlling hazardous chemicals in microreactors: Synthesis with iodine azide

• Johan C. Brandt and
• Thomas Wirth

Beilstein J. Org. Chem. 2009, 5, No. 30, doi:10.3762/bjoc.5.30

• interesting approach using solid support [32], but these compounds are usually unsuitable for applications in microreactors because of their poor solubility or they would require a different microreactor set-up that would allow solid supported reagents [33]. For better comparison with literature procedures

Polyionic polymers – heterogeneous media for metal nanoparticles as catalyst in Suzuki–Miyaura and Heck–Mizoroki reactions under flow conditions

• Klaas Mennecke and
• Andreas Kirschning

Beilstein J. Org. Chem. 2009, 5, No. 21, doi:10.3762/bjoc.5.21

• close proximity to the ammonium group by means of ion exchange (Scheme 1). In the following, the active Pd particle is generated upon reduction with a solution of sodium borohydride. A particular benefit of the resulting solid support is the stabilization of the generated nanoparticles by the polymer

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• yield observed between each run and without the need for catalyst regeneration, providing 78% total yield of 14 with 88% ee. Cinchona alkaloid derivatives have been featured in a number of solid support-based continuous flow asymmetric reactions. For example, a Wang-resin supported quinine derivative

A biphasic oxidation of alcohols to aldehydes and ketones using a simplified packed- bed microreactor

• Andrew Bogdan and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2009, 5, No. 17, doi:10.3762/bjoc.5.17

• it enables facile removal and recycling. We recently reported the development of an effective solid support for use in packed-bed microreactors [39], AMBERZYME® Oxirane (AO, 1), a commercially available resin with pendant epoxide functionalities designed for enzyme immobilization. AO is readily

• , increasing the safety of large-scale oxidations. Furthermore, it was determined that the use of a packed-bed microreactor facilitates efficient mixing of a biphasic system without destroying the solid support, a common problem with stirred systems [4]. Results and Discussion Previously we reported that

Silica- bound benzoyl chloride mediated the solid- phase synthesis of 4H-3,1-benzoxazin- 4-ones

• Kurosh Rad-Moghadam and
• Somayeh Rouhi

Beilstein J. Org. Chem. 2009, 5, No. 13, doi:10.3762/bjoc.5.13

• with 2-benzoylaminobenzoic acid was chosen as the model. After completion of the model reaction the solid support was separated by filtration, washed with dichloromethane, dried in oven and then refluxed in excess thionyl chloride. The recovered SBBC was subjected to the next run of the model reaction

• developed for preparation of 2-substituted 4H-3,1-benzoxazin-4-ones. The main advantages of this process are the recyclability of the solid support and self release of products from the linker as a concomitant with their formation. Therefore, good yields of the products are obtained under relatively mild

• because reactions with a loaded substrate can be manually sequenced and driven to higher yields by using excess reagents, which are subsequently removed by simple filtration [1][2][3][4][5][6][7]. Conventionally, solid-phase synthesis referred to approaches in which the substrate was loaded onto the solid

N-acylation of ethanolamine using lipase: a chemoselective catalyst

• Mazaahir Kidwai,
• Roona Poddar and
• Poonam Mothsra

Beilstein J. Org. Chem. 2009, 5, No. 10, doi:10.3762/bjoc.5.10

• less reaction time, taking only 4–5 min on solid support and 40–50 min in solution phase while low yields were obtained conventionally even after 4–5 h (Figure 1). In the microwave, the heating is homogenous whereas conventional energy transfer through contact, is comparatively slow and not so

• phase and solid support there is negligible decrease in activity even in run IV (Table 3). Microwave assisted solid media versus microwave-assisted solution phase Better results were obtained with the solid support in comparison to solution phase. Under microwave irradiation, the solid support acts as

• medium to transfer energy, leading to a significant improvement in reactivity. The reason can be attributed to the fact that microwave irradiation coupled with solid support facilitate the evaporation of by products H2O/EtOH shifting the equilibrium in the forward direction (Table 4 and Table 5) [24]. In

The first preparative solution phase synthesis of melanotan II

• Vladimir V. Ryakhovsky,
• Georgy A. Khachiyan,
• Nina F. Kosovova,
• Elena F. Isamiddinova and
• Andrey S. Ivanov

Beilstein J. Org. Chem. 2008, 4, No. 39, doi:10.3762/bjoc.4.39

• and Discussion To date, several accounts of solid phase synthesis of peptide 2 have been reported. A representative one, reported by Hruby and co-workers, exploited p-methylbenzhydrylamine resin (pMBHA) as the solid support and tert-butyloxycarbonyl (Boc) tactics for temporary protection of α-amino