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

• ; solution B: 0.059% TFA in 80% acetonitrile). The elution was monitored at 214 nm. The peptides were assayed for purity by analytical HPLC and ESIMS. The peptides were coupled to aminophalloidin through the hetero-bifunctional cross-linking agent SPDP (3-(2-pyridyldithio)propionic acid N-hydroxysuccinimide

• = 27500), and monomethoxy-polyethyleneglycolamine (Mr = 810, 5200, 22600) were coupled to aminophalloidin by the amine-reactive homo-bifunctional cross-linking reagents DSP (dithiobis(succinimidylpropionate); Lomant’s reagent) with cleavable disulfide group, or DSS (disuccinimidyl suberate) containing a

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

• reveal a functional group for ready conjugation to array surfaces and carrier proteins. Since the first successful automated system for solid-phase oligosaccharide synthesis was introduced [7], alternative linker strategies have been explored [8][9][10][11][12]. Recently, a bifunctional amino–ester

• 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

• release of the product, and this was not examined. As the new bifunctional resins 11 and 16 contain the additional Zemplén cleavage site, the product of this dominant but undesired reaction was evident. Second, the observation that reducing the concentration of the glycosylation agent caused an increase

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

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

• thiochromenes; and (3) Organocatalytic aza-Michael reactions to access functionalized 1,2-dihydroquinolines, using chiral proline and its derivatives (Figure 2), chiral bifunctional thioureas, cinchona alkaloids and other organocatalysts (Figure 3). For each reaction, the initial screening result of various

• employing a chiral pyrrolidine bearing a 2-mercaptopyridine moiety as organocatalyst (VII) and simple α-amino acids, such as tert-leucine, as co-catalyst. The asymmetric transformation proceeds by simultaneous activation of cyclic enones 13 and aldehyde 1 by the bifunctional catalyst VII and the amino acid

• poor enantioselectivity (5–17% ee) (Scheme 16). Very recently, Schreiner et al. [63] reported a bifunctional thiourea XXXIb catalyzed tandem reaction of salicyl-N-tosylimines 33 with nitroolefins 27 in toluene at room temperature for the synthesis of nitrochromenes 28, which resulted in poor yield and

Metal–ligand multiple bonds as frustrated Lewis pairs for C–H functionalization

• Matthew T. Whited

Beilstein J. Org. Chem. 2012, 8, 1554–1563, doi:10.3762/bjoc.8.177

• activate some of the most challenging substrates. One phenomenally useful example of heterolytic H–H cleavage across a ruthenium–amide bond, somewhat related to those described above, is found in Noyori's ruthenium hydrogenation catalysts, which utilize metal-ligand bifunctional pathways both for breaking

Mannose-decorated cyclodextrin vesicles: The interplay of multivalency and surface density in lectin–carbohydrate recognition

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2012, 8, 1543–1551, doi:10.3762/bjoc.8.175

• demonstrate the interaction of monovalent bifunctional guest molecules, containing a maltose or lactose unit and an adamantane unit, with cyclodextrin vesicles, and their ability to agglutinate with lectins [28]. We also showed that agglutination requires a critical density of carbohydrate ligand on the

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

• Tatyana E. Shubina,
• Matthias Freund,
• Sebastian Schenker,
• Timothy Clark and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168

• Organic Chemistry I, University of Erlangen-Nuremberg, Henkestraße 42, 91054, Erlangen, Germany 10.3762/bjoc.8.168 Abstract A new guanidine-thiourea organocatalyst has been developed and applied as bifunctional organocatalyst in the Michael addition reaction of diethyl malonate to trans-β-nitrostyrene

• . Extensive DFT calculations, including solvent effects and dispersion corrections, as well as ab initio calculations provide a plausible description of the reaction mechanism. Keywords: bifunctional organocatalyst; DFT calculations; guanidine-thiourea; Michael addition; organocatalysis; transition states

• ; Introduction In recent years bifunctional compounds have found frequent applications as organocatalysts in modern synthetic organic chemistry [1][2][3][4][5][6][7][8]. Over the past decade, different catalytic methodologies have been reported that use chiral thiourea-based bifunctional molecules [9][10][11][12

A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• electrophilicity scales in [4]. When proline or structurally related bifunctional catalysts are employed, the mechanism depicted in Figure 17 has to be modified. List and Houk explained the high enantioselectivity of proline catalyzed reactions of aldehydes or ketones with electrophiles by the transition state TS

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• ) (Figure 2). All of these screened catalysts are bifunctional compounds possessing hydrogen-bonding donor and acceptor moieties. Catalysts based on thiourea and squaramide differ from each other in their possible hydrogen-bond angles, rigidity of conformation, and pKa values [20]. Although the two

• , the increase in temperature resulted in a small drop in stereoselectivity for the model reaction with catalyst VII. The mechanism of the reaction is believed to be similar to that previously reported for 1,3-dicarbonyl compounds and acyl phosphonates [23]. Squaramide IX is a bifunctional catalyst that

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

• categories, for example, being mono- or bis-thioureas. Furthermore, they can be mono- or bifunctional with variably weak amine (primary, secondary, tertiary) or amide groups attached. Figure 2 illustrates a few selected examples of the aforementioned chiral thioureas which have successfully been applied in

• was known for chiral bifunctional amine-based sulfonamides that two hydrogen bond donors were not strictly required in the enantioselective organocatalytic ring opening of meso-anhydrides [48][54], this particular transformation was chosen as initial test reaction. Cyclic anhydride 4 served as

• good yield (66%) within 24 h. Disappointingly, however, the product was racemic. In general, two concomitant events are discussed for bifunctional organocatalysts such as amino group-containing sulfonamides or thioureas: One is the activation of the anhydride carbonyl group by hydrogen bonding to the

Organocatalytic asymmetric Michael addition of unprotected 3-substituted oxindoles to 1,4-naphthoquinone

• Jin-Sheng Yu,
• Feng Zhou,
• Yun-Lin Liu and
• Jian Zhou

Beilstein J. Org. Chem. 2012, 8, 1360–1365, doi:10.3762/bjoc.8.157

• [26][27]. To construct the C3 quaternary stereogenic carbon center, we have designed a novel cinchona alkaloid-based phosphoramide bifunctional catalyst to realize a highly enantioselective Michael addition of both unprotected 3-alkyl- and 3-aryloxindoles to nitroolefins [28]. Based on these results

• -phenyloxindole 1a and 1,4-naphthoquinone (2a), with ethyl acetate (EtOAc) as the solvent at 0 °C (Table 1, Figure 1). A variety of bifunctional cinchona alkaloid-derived catalysts 5–9 were first tried, aiming to facilitate the reaction by the dual activation of both reaction partners, with H-bonding donor moiety

• TLC and NMR analysis of the crude reaction mixture. While the simple quinine and quinidine as catalysts could deliver product 3a in 59% ee (Table 1, entry 2), all other bifunctional catalysts turned out to be much less enantioselective (Table 1, entries 3–5). However, the dinuclear Brønsted base

Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones

• Chunhui Jiang,
• Fangrui Zhong and
• Yixin Lu

Beilstein J. Org. Chem. 2012, 8, 1279–1283, doi:10.3762/bjoc.8.144

• , catalyzed by cinchonine-derived bifunctional thiourea catalyst has been described. The desired β-amino ketones were obtained in excellent yields and with moderate to good enantioselectivities. Keywords: decarboxylative addition; β-keto acid; Mannich reaction; organocatalysis; Introduction Chiral β-amino

• tosylimine 1a and β-keto acid 2a in the presence of a range of bifunctional catalysts (Table 1). We first evaluated the catalytic effects of several cinchona alkaloid derivatives. Commercially available cinchonidine (CD-1) led to the formation of the product with disappointing enantioselectivity (Table 1

• , entry 1). Quinine-derived sulfonamide [40], β-isocupreidine (β-ICD) [41][42] and biscinchona alkaloid (DHQ)2AQN were all found to be poor catalysts (Table 1, entries 2–4). On the other hand, cinchona alkaloid derived bifunctional thiourea tertiary amine catalysts afforded much improved results (Table 1

Synthesis and anion recognition properties of shape-persistent binaphthyl-containing chiral macrocyclic amides

• Marco Caricato,
• Nerea Jordana Leza,
• Claudia Gargiulli,
• Giuseppe Gattuso,
• Daniele Dondi and
• Dario Pasini

Beilstein J. Org. Chem. 2012, 8, 967–976, doi:10.3762/bjoc.8.109

• of binding of the difunctional anionic guests within the macrocycle, or the formation of aggregates of several macrocyclic units, held by the bifunctional anionic guests binding to a single amide of each macrocycle, cannot be ruled out at the present stage. Further studies are in progress to unravel

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• -galactopyranosyl)oxy]methyl}furan-3-yl)methyl hydrogen sulfate (GSF), which is a bifunctional saccharide mimetic consisting of a bis-hydroxymethylated furan core, a galactose residue and a sulfate group. It represents a mimetic of the GAG-subunit and may interact with the cell-surface or the ECM. We report the

Enantioselective Michael addition of 2-hydroxy-1,4-naphthoquinones to nitroalkenes catalyzed by binaphthyl-derived organocatalysts

• Saet Byeol Woo and
• Dae Young Kim

Beilstein J. Org. Chem. 2012, 8, 699–704, doi:10.3762/bjoc.8.78

• Saet Byeol Woo Dae Young Kim Department of Chemistry, Soonchunhyang University, Asan, Chungnam, 336-745, Korea 10.3762/bjoc.8.78 Abstract The highly enantioselective Michael addition of 2-hydroxy-1,4-naphthoquinones to nitroalkenes, promoted by binaphthyl-modified chiral bifunctional

• , bifunctional tertiary-amine thioureas, thiophosphorodiamides, and squaramide-based organocatalysts [34][35][36]. Findings In the framework of our research program for the development of synthetic methods for the enantioselective construction of stereogenic carbon centers [37][38][39][40][41][42], we recently

• reported the enantioselective Michael addition of active methines to nitroalkenes [43][44]. Herein, we describe the direct enantioselective Michael addition of 2-hydroxy-1,4-naphthoquinone with nitroalkenes, catalyzed by bifunctional organocatalysts (Figure 1) that bear both central and axial chiral

Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles

• Pavol Jakubec,
• Dane M. Cockfield,
• Madeleine Helliwell,
• James Raftery and
• Darren J. Dixon

Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64

• -component coupling reaction (Scheme 8). As described in our previous communication [61], the employment of bifunctional catalyst 9 [54][55] in a highly stereoselective two-stage one-pot cascade led to the formation of enantiomerically highly enriched spirocycle (+)-1a (Scheme 8). In a repeat of the process

Synthesis and characterization of new diiodocoumarin derivatives with promising antimicrobial activities

• Hany M. Mohamed,
• Ashraf H. F. Abd EL-Wahab,
• Ahmed M. EL-Agrody,
• Ahmed H. Bedair,
• Fathy A. Eid,
• Mostafa M. Khafagy and
• Kamal A. Abd-EL-Rehem

Beilstein J. Org. Chem. 2011, 7, 1688–1696, doi:10.3762/bjoc.7.199

• compounds 3 and 7 showed the corresponding molecular ion peaks at m/z 460 (M+, 2.6%) and m/z 469 (M+, 18.5%). The fragmentation pattern of compounds 3 and 7 are illustrated in Scheme 2. Reactions of 3 with 4-aminophenylethanol or p-aminophenol, or with potentially bifunctional amino acids (anthranilic acid

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

• we illustrate a unique use of catalysts in flow, but we provide additional insight into the role of additives in proline-catalyzed reactions. Results and Discussion In our previously published batch work, we found that the combination of L-proline and bifunctional urea 3a greatly accelerated the rate

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• product. The initiation module of curacin biosynthesis contains a GCN5-related N-acetyltransferase (GNAT) domain. These enzymes typically catalyze acyl transfer to a primary amine. The curacin GNAT, however, was shown to be bifunctional and to exhibit decarboxylase/S-acetyltransferase activities [45]. The

• antimicrobial activities (lantibiotics) [68]. Cyanobacteria were shown to frequently encode LanM type enzymes, i.e., bifunctional enzymes catalyzing both dehydration and cyclization reactions [68]. An interesting phenomenon was observed for the strain Prochlorococcus MIT9313, which is a single-celled planktonic

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

• -mercaptoamino group present in Cys. When the thiol group in Hcy is methylated, as in methionine, its power to bind to the sensor is completely lost. As none of the bifunctional α-amino acids caused any fluorescence quenching of the probe, the presence of β-mercaptoamino moiety in cysteine may confer a

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

• María Martín-Rodríguez,
• Carmen Nájera,
• José M. Sansano,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2011, 7, 988–996, doi:10.3762/bjoc.7.111

• in 1,3-DC compared to other catalysts with different stoichiometry or anion nature. The gold complex (Sa,Sa)-14 was prepared according to the literature [39] and immediately used in the cycloaddition in the absence of base because of its bifunctional behaviour, namely the activation of the basic

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• malononitriles 375 and N-Boc-protected imines 374 (Scheme 60) [176]. In the alkyne hydroamination (which is based on a bifunctional organocatalytic Mannich-type reaction, subsequent gold-catalyzed alkyne hydroamination and isomerization) thiourea-based hydrogen bonding organocatalyst 373 and PPh3AuNTf2 proved to

Advances in synthetic approach to and antifungal activity of triazoles

• Kumari Shalini,
• Nitin Kumar,
• Sushma Drabu and
• Pramod Kumar Sharma

Beilstein J. Org. Chem. 2011, 7, 668–677, doi:10.3762/bjoc.7.79

• well as in increasing solubility [20]. Moreover, triazoles can function as attractive linker units which could connect two pharmacophores to give an innovative bifunctional drug, and thus have become increasingly useful and important in constructing bioactive and functional molecules [21][22][23

Regioselective ester cleavage during the preparation of bisphosphonate methacrylate monomers

• Kamel Chougrani,
• Gilles Niel,
• Bernard Boutevin and
• Ghislain David

Beilstein J. Org. Chem. 2011, 7, 364–368, doi:10.3762/bjoc.7.46

• ester function without affecting the methacrylate ester. Keywords: bifunctional monomer; phosphonic acid; regioselective ester cleavage; Introduction The potential applications for polymer products containing phosphorus are numerous; dental adhesives, ion-exchange resins and adhesion promotors are

• use of phosphonate-type methacrylates for the same purpose [8][9]. In the domain of polymer-based materials exhibiting specific properties, bifunctional monomers bearing a methacrylate function and a bisphosphonate function are recognized as useful building blocks for dental materials [11][12][18][19

• methacrylate monomers We have designed new bifunctional monomers 1a–7a bearing a methacrylate and an amino(bismethylene)bisphosphonate (Scheme 1) linked by an aliphatic or an aromatic spacer [20][21]. To the best of our knowledge, only a single acrylate containing monomer 8 has been previously synthesized and

Kinetics and mechanism of vanadium catalysed asymmetric cyanohydrin synthesis in propylene carbonate

• Michael North and
• Marta Omedes-Pujol

Beilstein J. Org. Chem. 2010, 6, 1043–1055, doi:10.3762/bjoc.6.119

• in the area of asymmetric cyanohydrin synthesis [1], mostly using trimethylsilyl cyanide (TMSCN) as the cyanide source to produce enantiomerically enriched silyl-protected cyanohydrins, which can readily be converted into other, pharmaceutically important, bifunctional units, such as α-hydroxy acids